EDE015-b Molecular Imaging Case of the Day

Education Exhibits Location: NA

Participants Moderator Umar Mahmood MD, PhD Research Grant, Sabik Medical Inc Rahul Anil Sheth MD : Nothing to Disclose Manuela Cristina Matesan MD, PhD : Nothing to Disclose David H. Lewis MD : Research Consulant, Eli Lilly and Company Satoshi Minoshima MD, PhD : License agreement, General Electric Company Research Grant, Koninklijke Philips Electronics NV Research Grant, Hitachi, Ltd Research Consultant, Hamamatsu Photonics KK Grant, Nihon Medi-Physics Co, Ltd Research Grant, Astellas Group Research Grant, Seattle Genetics, Inc Baris Turkbey MD : Nothing to Disclose Peter L. Choyke MD : Researcher, Koninklijke Philips NV Researcher, General Electric Company Researcher, Siemens AG Researcher, iCAD, Inc Researcher, Aspyrian Therapeutics, Inc Researcher, ImaginAb, Inc Researcher, Aura Daniel Pryma MD : Research Grant, Siemens AG Research Grant, Molecular Insight Pharmaceuticals, Inc Speaker, IBA Molecular Advisory Board, Bayer AG Michael David Farwell MD, MA : Nothing to Disclose David A. Mankoff MD, PhD : Speaker, Koninklijke Philips NV Speaker, Siemens AG Speaker, General Electric Company Yusuf Menda MD : Research Grant, Advanced Accelerator Applications John Sunderland PhD : Research Grant, Siemens AG Ravi A. Madan MD : Nothing to Disclose

MIE001-b Oncogenic Osteomalacia, What Does It Look Like? From SPECT to Plain Films with Pathologic Correlation

Education Exhibits Location: NA

Participants Jesus Alejandro Gabutti MD (Presenter): Nothing to Disclose Ailan Hitandhui Barrientos-Priego MD : Nothing to Disclose Joaquin Nunez Gomez MD : Nothing to Disclose Daniela Canaviri MD : Nothing to Disclose Fritz Hofmann MD : Nothing to Disclose Jorge Vazquez-Lamadrid MD : Nothing to Disclose Fernando Cano MD : Nothing to Disclose TEACHING POINTS To explain the pathophysiology con oncogenic osteomalacia. To explain the importance of molecular imaging, with special emphasis in SPECT-CT for the correct diagnosis. To show and explain the main imaging findings in MRI, US, CT and plain films of mesenchymal tumor, systemic manifestations, complications and consequences of a delay diagnosis. To emphasize the importance of the radiologist in the approach of a patient of suspected oncogenic osteomalacia. TABLE OF CONTENTS/OUTLINE Introduction: epidemiology and pathogenesis. Clinical and laboratory findings. Imaging work-up, indications and algorithm. SPECT and SPECT-CT findings, radiotracers and technique. Other molecular imaging methods. Review of cases with radiologic-pathologic correlation: MRI and ultrasound appearance of the mesenchymal tumor. CT and plain films of the systemic manifestations and complications. Summary of the teaching points and conclusion. MIE002-b Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI): Clinical Advances and Implications in Neuroimaging of Epilepsy

Education Exhibits Location: NA

Participants Emmanuel C. Obusez MD (Presenter): Nothing to Disclose Shetal N. Shah MD : Nothing to Disclose Bandar Osaid Safar MD : Nothing to Disclose Unni K. Udayasankar MD, FRCR : Nothing to Disclose Guiyun Wu MD : Nothing to Disclose Stephen Edward Jones MD, PhD : Nothing to Disclose TEACHING POINTS 1. Emphasize the clinical significance of simultaneous PET/MRI in the improving the detection of epilepsy foci. 2. Illustrate with simultaneous fused-FDG-PET/MRI findings of epileptic foci. TABLE OF CONTENTS/OUTLINE 1. Briefly review the role of MRI in epilepsy a. Discuss current MRI imaging findings and limitations in the evaluation of epilepsy foci. Limited to focal cortical dysplasia, meso temporal sclerosis, polymicrogyria and heterotopia. 2. Describe current technical advances in PET/MRI and its use in neuroimaging. 3. Discuss the clinical utility of fused-FDG-PET/MRI for evaluation of epilepsy foci and advantages over structural MRI. Fused-PET/MRI is a modality that offers superior diagnostic advantages. Patients with medically refractory epilepsy may be candidates for surgery. This cohort of patients may have a positive surgical outcome with the identification of epileptic foci on MRI. However, some patients show indeterminate or no evidence of structural abnormality on MRI. In these subset of patients, fused-FDG-PET/MRI is increasing being used as a tool to enhance pre-surgical identification of epileptic foci. Learn the clinical utility of fused-FDG-PET/MRI and its advantages - such as new regions of hypometabolic epileptic foci not seen on MRI and ability to delineate anatomic boundaries of hypometabolism not identified on PET. MIE003-b Utility of 18F-FDG PET/CT and 11C-Acetate PET/CT in Restaging of Prostate Cancer: A Review of the Literature

Education Exhibits Location: NA

Participants Erika Morrongo Bastida MD (Presenter): Nothing to Disclose Juan Pablo Chavez Torres MD : Nothing to Disclose Ailan Hitandhui Barrientos-Priego MD : Nothing to Disclose Jose Rafael Garcia Ortiz MD : Nothing to Disclose Maria Mayela Leon Sanchez : Nothing to Disclose Irma Soldevilla-Gallardo : Nothing to Disclose TEACHING POINTS 1.To review differences in the metabolic pathway and biodistribution of each radiopharmaceutical 2.To know the use that has been given in the literature to 18F FDG PET / CT and 11C-Acetate PET/CT in the restaging of prostate cancer 3.To identify specific conditions in each patient for the best selection of the radiopharmaceutical that provides more information in the restaging of prostate cancer TABLE OF CONTENTS/OUTLINE

Overview of prostate cancer Properties of 18F-FDG and 11C-Acetate Indicators of prostate cancer recurrence Review of the utility of 18F FDG PET/CT and 11C-Acetate in the restaging of prostate cancer Choice of Radiopharmaceutical Example images

MIE100 New Insights in Molecular Imaging of Venous Thromboembolism

Education Exhibits Location: NA

Participants Sina Houshmand MD : Nothing to Disclose Ali Salavati MD, MPH (Presenter): Nothing to Disclose Soren Hess : Nothing to Disclose Thomas J. Werner : Nothing to Disclose Abass Alavi MD : Nothing to Disclose TEACHING POINTS To review different molecular imaging techniques for diagnosis and assessment of venous thromboembolism (VTE). To review applications of clinical routine molecular imaging techniques for diagnosis of VTE and tumor thrombosis. TABLE OF CONTENTS/OUTLINE Venous thromboembolism (VTE) is a blood clotting disorder mostly presenting as deep vein thrombosis (DVT) and pulmonary embolism (PE) which affects up to 600,000 individuals in United States each year. Clinical symptoms of VTE are nonspecific and sometimes misleading. Additionally, side effects of available treatment plans for VTE are significant. Therefore, medical imaging plays a crucial role in proper diagnosis and avoidance from over/under diagnosis, which exposes the patient to risk. Molecular imaging techniques with different tracers have been studied for diagnosis of VTE and have shown promise in aiding the conventional structural imaging of VTE. In this exhibit we will briefly review following topics: 1. Molecular imaging methods for diagnosis of VTE i. SPECT / scintigraphy a. Ventilation-perfusion scan b. Anti D-Dimer c. GP IIb/IIIa Cyclic RGD Peptide d. Antifibrin antibodies ii. PET/CT a. FDG b. EP-2104R iii. Near Infrared fluorescence imaging MIE101 The Emerging Role of 18F-FDG and Sodium 18F Fluoride PET/CT in the Assessment of Atherosclerotic Plaques: An Update [ MI Scavenger Hunt! ]

Education Exhibits Location: NA

Participants Ali Salavati MD, MPH (Presenter): Nothing to Disclose Sina Houshmand MD : Nothing to Disclose Thomas J. Werner : Nothing to Disclose Benjapa Khiewvan : Nothing to Disclose Saeid Gholami MD : Nothing to Disclose Abass Alavi MD : Nothing to Disclose TEACHING POINTS To review the advances in molecular imaging of atherosclerosis and vessel wall inflammation using FDG-PET/CT and sodium 18F Fluoride -PET/CT. To review the impact of different methodological factors on vessel wall imaging and quantification of 18F-FDG and sodium 18F Fluoride PET/CT scans. TABLE OF CONTENTS/OUTLINE 18F-FDG PET/CT is a noninvasive, accurate and reproducible imaging modality that can identify and quantify inflammatory processes and prognosticate the risk for acute cardiovascular disease. Imaging vascular calcification by sodium 18F fluoride PET/CT can possibly improve cardiovascular risk stratification by detecting calcification in vascular wall and also differentiate active from indolent calcification. In this review, we will discuss advances and improvements in application of FDG-PET/CT and sodium 18F Fluoride PET/CT in atherosclerotic plaque inflammation and effects of methodological factors on accurate quantification of vessel wall inflammation. 1) FDG-PET/CT 2) Sodium 18F Fluoride 3) Methodological factors i. Delayed time point ii. Pre-scan variables iii. FDG Uptake parameters a. Qualitative b. Semi-quantitative c. Quantitative MIE102 Clinical Utility of PET-MRI in Abdominopelvic Imaging

Education Exhibits Location: NA

Participants Maryam Gul (Presenter): Nothing to Disclose Ammar Ahmed Chaudhry MD : Nothing to Disclose Kevin S. Baker MD : Nothing to Disclose Abbas Ahmed Chaudhry BSc : Nothing to Disclose Mubashir Sheikh : Nothing to Disclose Marlene Leslie Zawin MD : Nothing to Disclose TEACHING POINTS

1- Review physical principles and techniques of PET-MRI (positron emission tomography-magnetic resonance imaging). 2- Discuss clinical utility of using functional information obtained from a PET scan and structural information obtained from MR imaging.

TABLE OF CONTENTS/OUTLINE Outline: 1. Physical principles and techniques of PET-MRI: review image acquisition and postprocessing 2. Utility of PET-MRI in oncology: role in initial tumor diagnosis, treatment planning and post-treatment follow-up 3. Role of PET-MRI in evaluation of infectious and inflammatory conditions (such as IgG4-related disease, etc) 4. Pearls and Pitfalls: Common pitfalls and controversies regarding PET-MRI in abdominopelvic radiology. 5. Future of PET- MRI: Discuss current challenges facing PET- MRI in radiology. Conclusion: PET-MRI is an emerging hybrid imaging modality offering detailed functional and structural imaging with promising clinical applications especially in the field of oncology, infectious and inflammatory conditions. Familiarity with the technical and clinical aspects of PET-MRI along with knowledge of common pearls and pitfalls of PET-MRI will aid in better integration and relevant usage of this modality in clinical practice. MIE103 Improved Detection Sensitivity of Merkel Cell Carcinoma Liver Metastasis by SPECT-CT Octreoscan and FDG PET-CT

Education Exhibits Location: NA

Participants Jinchun Yan MD, PhD (Presenter): Nothing to Disclose Upendra Parvathaneni MBBS, FRANZC : Nothing to Disclose TEACHING POINTS 1. SPECT-CT has increased contrast resolution than planar imaging and therefore often bears higher detection sensitivity. 2. Octreoscan is a useful imaging modality for detecting neuroendocrine tumors that express somatostatin receptors. TABLE OF CONTENTS/OUTLINE Merkel cell carcinoma (MCC) is a cutaneous malignancy of neuroendocrine origin with a high propensity for distant metastases. The prognosis is significantly worse for patients with metastatic spread; 5 year overall survival is 80% for stage I versus 20% for stage IV disease. 111In-pentetreotide imaging (Octreoscan) is a useful imaging modality for detecting neuroendocrine tumors that express somatostatin receptors. It helps in the management of MCC by identifying clinically occult metastases for staging and during surveillance. It also determines whether treatment with Octreotide is indicated. However, planar 111 In-pentetreotide images do not always detect liver metastases due to high background liver uptake. SPECT-CT can offer better contrast resolution compared to planar imaging. FDG PET-CT images correlate well with the SPECT-CT. MIE105 Potential Value of 18F-FDG PET/CT in Diagnosis and Therapy Evaluation of Relapsing Polychondritis (RP): A Rare Autoimmune Disease

Education Exhibits Location: NA

Participants Susann-Cathrin Schuele (Presenter): Research Grant, Siemens AG Christian la Fougere : Nothing to Disclose Theodoros Xenitidis : Nothing to Disclose Theodoros Xenitidis : Nothing to Disclose Joerg henes : Nothing to Disclose Konstantin Nikolaou MD : Speakers Bureau, Siemens AG Speakers Bureau, Bracco Group Speakers Bureau, Bayer AG Christina Pfannenberg MD : Nothing to Disclose TEACHING POINTS Teaching Points • To present the typical RP manifestations in FDG-PET/CT • To underline the value of FDG-PET/CT for initial diagnosis, especially if laboratory and clinically results are inconsistent • To illustrate PET/CT as an adequate tool for therapy monitoring for vitality assessment of RP • To describe the value of FDG-PET/CT for detection of RP-associated diseases TABLE OF CONTENTS/OUTLINE Outline (1) PET/CT for primary staging (case example 1) : 18F-PET/CT was not only suspicious for RP, but also exactly defined the extent of acute inflammation (auricular cartilage, tracheal-bronchial system) in a patient with fever, night sweat and swelling of the right ear, clinically suspect for vasculitis or a malignant tumour. (2) PET/CT for therapy monitoring (case example 2): PET/CT excluded in one case a relapse despite clinical symptoms, whereas in another case diagnosed a relapse despite normal laboratory findings. (3) PET/CT for detection/exclusion of RP-associated diseases (case example 3): PET/CT excluded vasculitis in one patient and malignant tumors in two patients with night sweat. PET/CT excluded vital RP before replacement of descending aorta in a patient with known RP and elevated CRP. MIE109 A Review of Bench to Bedside Molecular Functional Imaging in Translational Cancer Medicine: To Image or to Imagine? [ MI Scavenger Hunt! ]

Education Exhibits Location: NA

Participants Abhishek Mahajan MD (Presenter): Nothing to Disclose Sandip Basu MBBS, MD : Nothing to Disclose Meenakshi Haresh Thakur MD : Nothing to Disclose TEACHING POINTS Molecular functional imaging has given a newer insight to the medical imaging and has diversified the role of imaging in the field of the translational cancer medicine and has an indispensible role to play in screening, early diagnosis, staging, predicting prognosis, therapy delivery, therapy monitoring and follow-up. Overall there has been a significant development in the field of molecular imaging and its utilisation in the perspective of the biomedical research which has led to better understanding of the signalling pathways in the tumorigenesis and novel drug discoveries. The future of molecular functional imaging in the coming era is its exploitation into understanding the gene expression profiling in-vivo and optimising the patient specific therapies using gene expression profiling. Quantitative molecular functional imaging, in conjunction with quantitative structural imaging, will be the future of 'personalized radiology,' 'personalized oncology,' 'personalized medicine,' and of oncologic research in the 21st century and beyond. TABLE OF CONTENTS/OUTLINE • Cancer And Molecular Functional Imaging (MFI) • MFI Of Gene Expression, Receptors And Signalling Pathways • MFI of Multidrug-Resistance In Cancer • MFI Of Extracellular Matrix And Its Key Components • MFI Of Neoangiogenesis, Hypoxia And Metabolism • MFI And Small Animal Imaging MIE110 DWI vs 18-FDG PET/CT: Which Technique for Which Clinical Scenario? [ MI Scavenger Hunt! ]

Education Exhibits Location: NA Selected for RadioGraphics

Participants Antonio Luna MD (Presenter): Nothing to Disclose Joan C. Vilanova MD, PhD : Nothing to Disclose Sandra Baleato Gonzalez MD : Nothing to Disclose Roberto Garcia Figueiras MD : Nothing to Disclose Mariano Volpacchio MD : Nothing to Disclose Christine O. Menias MD : Nothing to Disclose TEACHING POINTS

Highlight the complementary role of these techniques in the detection and staging of different body tumors Review which of these techniques is more adequate for common clinical scenarios in oncology

TABLE OF CONTENTS/OUTLINE

1. Introduction 2. Staging - WB-DWI vs PET-CT - N-staging - M-staging: liver, brain, lung and bone metastases - Performance in staging of NSCLC, breast cancer, prostate cancer, malignant melanoma, colorectal cancer, lymphoma, multiple myeloma and others 3. Therapy monitoring 4. Prediction of treatment response 4. Prediction of treatment response 5. Postreatment surveillance 6. Conclusions

MIE111 Multiparametric Imaging in Oncology: Deconstructing Tumor Microenvironment [ MI Scavenger Hunt! ]

Education Exhibits Location: NA

Participants Roberto Garcia Figueiras MD (Presenter): Nothing to Disclose Anwar Roshanali Padhani MD : Advisory Board, Acuitas Medical Ltd Advisory Board, Siemens AG Speakers Bureau, Siemens AG Researcher, Siemens AG Speakers Bureau, Johnson & Johnson Ambros Johannes Beer MD : Nothing to Disclose Sandra Baleato Gonzalez MD : Nothing to Disclose Antonio Luna MD : Nothing to Disclose Joan C. Vilanova MD, PhD : Nothing to Disclose Laura Oleaga : Nothing to Disclose Maria Cruz Ageitos Casais MD : Nothing to Disclose Anxo Martinez De Alegria MD : Nothing to Disclose TEACHING POINTS Cancers are complex, evolving, multiscale systems characterized by profound spatial and temporal heterogeneity in their phenotype. Actually, there is an opportunity to perform multiparametric imaging (MPI) at a variety of organ sites and with many clinical roles. The aim of this exhibit is: -To emphasis that functional and molecular imaging (FMI) imaging techniques may yield an added information of biological tumor phenotype and of the effects of therapies. -To learn about the biological correlates of MPI based on different FMI techniques: dynamic contrast-enhanced ultrasound, perfusion CT, dynamic contrast-enhanced MRI, dynamic susceptibility MRI, diffusion-weighted MRI, MR spectroscopy imaging, BOLD-MRI, PET, or SPECT. -To evaluate the value of MPI approach in clinical oncology, including tumor diagnosis, prognosis, response to therapy, or relapse and drug development. TABLE OF CONTENTS/OUTLINE 1. Why do we need MPI in oncology? 2. Tumor hallmarks in imaging and tumor microenvironment. 3. MPI in oncology: Basic principles. 4. MPI in clinical practice: a) The established roll of MPI imaging in tumors (prostate, breast and brain tumors). b) New approaches to tumoral phenotype based in MPI. c) MPI in tumor evaluation: when discrepancies are biological meaningful. d) MPI for monitoring tumor response evaluation. MIE114 Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

Education Exhibits Location: NA

Participants Harald Ittrich MD (Presenter): Nothing to Disclose Nina Raabe MD : Nothing to Disclose Kersten Peldschus MD : Nothing to Disclose Michael Gerhard Kaul : Nothing to Disclose Gerhard B. Adam MD : Nothing to Disclose TEACHING POINTS 1. SPIO can be used for diagnostic MRI and therapy and may qualify for MPI. 2. Monodisperse SPIO improve physicochemistry and pharmacodynamics. 3. SPIO in targeted probes enable in in vitro diagnostic imaging (μNMR). TABLE OF CONTENTS/OUTLINE SPIO can be used to image anatomical, cellular and molecular changes. Clinical applications range from MRA to the imaging of tumors, lymph nodes, CNS, atherosclerotic plaque and thrombosis. New experimental approaches describe undirected SPIO trapping in inflammation and tumors and directed accumulation of SPIO ligands in/on tumor and apoptotic cells, infarction, inflammation and degeneration in cardiovascular and neurological diseases, in atherosclerosis or thrombi. Stem cell labeling allows imaging of cell therapies or transplant rejections. SPIO coupling to ligands, radio- and/or chemotherapeutics, embedding in carrier systems or activatable smart sensor probes enable molecular tumor therapies or the imaging of metabolic and enzymatic processes. Monodisperse SPIO may improve SPIO-based MRI in the future and as targeted probes in diagnostic magnetic resonance. Chip-based μNMR may improve in vitro analysis methods for biomarkers, pathogens and tumor cells. Magnetic particle imaging (MPI) offers new applications for SPIO in cardiovascular, oncological, cellular and molecular diagnostics and therapy. MSE120 The Devil is in the DNA: A Comprehensive Review of Rare Malignancies that Warrant Genetic Testing

Education Exhibits Location: MS Community, Learning Center Selected for RadioGraphics

Participants Venkata S. Katabathina MD : Nothing to Disclose Venkata S. Katabathina MD : Nothing to Disclose Gowri Gutti MD (Presenter): Nothing to Disclose Abhinav Suri : Nothing to Disclose Sandhya Vinu-Nair : Nothing to Disclose Christine O. Menias MD : Nothing to Disclose Anil Kumar Dasyam MD : Nothing to Disclose TEACHING POINTS Review select, rare malignancies that are highly associated with hereditary cancer predisposition syndromes Discuss cytogenetic and molecular abnormalities of genetic conditions associated with these malignancies Describe cross-sectional imaging findings; role of imaging in the diagnosis and surveillance of patients and family members TABLE OF CONTENTS/OUTLINE Introduction Medullary thyroid carcinoma: Multiple endocrine neoplasia 2A and B - RET proto-oncogene Carcinoid tumors: MEN 1 - MEN 1 gene Leiomyosarcomas: Hereditary leiomyomatosis and renal cell carcinoma syndrome [fumarate hydratase gene] and Lynch syndrome [ DNA mismatch repair genes] Pheochromocytoma and Paraganglioma: Multiple endocrine neoplasia 2, von Hippel-Lindau syndrome, Neurofibromatosis type 1, Hereditary paraganglioma-pheochromocytomas, Max and TMEM127 gene mutations Adrenal cortical carcinoma: Li-Fraumeni syndrome ( p53 gene) Renal cell carcinoma - chromophobe, hybrid oncocytic, oncocytoma type: Birt-Hogg-Dube syndrome (Folliculin gene ) Fallopian tube and primary peritoneal cancers: Hereditary breast and ovarian cancer syndrome (BRCA gene) Diffuse gastric cancer: Hereditary diffuse gastric cancer syndrome (E-cadherin gene) Conclusion Awareness of rare malignancies associated with cancer predisposition syndromes will help radiologists to suggest appropriate genetic testing SSA12 Molecular Imaging (GYN/Breast Cancer)

Scientific Papers NM MR MI CT OB GU BR AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Sun, Nov 30 10:45 AM - 12:15 PM Location: S504CD

Participants Moderator Zaver Murzban Bhujwalla PhD : Nothing to Disclose Moderator Kathryn A. Morton MD : Nothing to Disclose

Sub-Events

SSA12-01 Tumor Detection with Activatable Cell Penetrating Peptide Dendrimers (ACPPD-Gd) versus Conventional Gadolinium Chelates at 3 Tesla Christopher Devin Malone MD (Presenter): Nothing to Disclose , Emilia Sue Olson MD, PhD : Nothing to Disclose , Robert Frederick Mattrey MD : Nothing to Disclose , Nadia Nashi : Nothing to Disclose , Tao Jiang PhD : Nothing to Disclose , Leslie Ellies : Nothing to Disclose , Roger Y. Tsien MD : Research Consultant, Avelas Biosciences, Inc Stockholder, Avelas Biosciences, Inc , Quyen Nguyen : Nothing to Disclose PURPOSE Matrix metalloproteinases-2 and -9 (MMP-2/-9) are upregulated in many aggressive tumors. We aimed to compare the tumor detection performance of a standard Gd-chelate to that of Gd-loaded MMP-2/-9 activatable cell-penetrating peptide dendrimers (ACPPD-Gd) using a murine tumor model representative of aggressive triple-negative breast cancer with 3T MR.

METHOD AND MATERIALS Using a protocol approved by the Institutional Animal Care and Use Committee, 2 of 4 inguinal breast fat pads of 16 albino C57BL/6 mice were inoculated with Py8119 cells and the other 2 with saline at random. MR at 3T was performed on 8 mice before and 2-3 minutes after 0.1mmol/kg gadobutrol and on 8 mice 24-hours after 0.036mmol/kg Gd of ACPPD-Gd on days 4, 9, and 14 after inoculation. T1w tumor signal was normalized to adjacent muscle and compared between agents and the non-contrast groups using analysis-of-variance. Experienced and trainee blinded readers assessed for the presence of tumor in each of the 4 breast regions. ROC curves were constructed and the area-under-the-ROC curve (AUC) calculated.

RESULTS Mouse mammary tumors imaged by MR at 3T 24 hours after ACPPD-Gd showed significantly greater T1w signal compared to tumors imaged 2-3 minutes after gadobutrol (1.57±0.2 vs. 1.25±0.13, p5mm3) were removed from the ROC analysis for the experienced observer (0.96 vs. 0.86, p=0.098), and more so for the trainee (0.86 vs. 0.69, p=0.04).

CONCLUSION ACPPD-Gd results in significantly more T1w signal in tumors compared to gadobutrol at 3T, resulting in increased conspicuity and improved detection for experienced and more so less experienced observers.

CLINICAL RELEVANCE/APPLICATION ACPPD-Gd improves tumor conspicuity, the performance of the less experienced observers, and may highlight early stage tumors that could be missed on T1w MR imaging at clinically relevant fields strengths and scan times.

SSA12-03 Amino Acid Transport Imaging of Breast Carcinoma via Anti-3-[18F] FACBC PET-CT: A Pilot Study Funmilayo Tade MD, MPH (Presenter): Nothing to Disclose , Oluwaseun Odewole MD, MPH : Nothing to Disclose , Oyeladun Oyenuga MD, MPH : Nothing to Disclose , Michael A. Cohen MD : Nothing to Disclose , Anna Irene Holbrook MD : Nothing to Disclose , Mary S. Newell MD : Nothing to Disclose , Bital Savir-Baruch MD : Nothing to Disclose , Toncred Styblo MD, MS : Nothing to Disclose , Mark M. Goodman PhD : Royalties, Nihon Medi-Physics Co, Ltd , David M. Schuster MD : Research funded, Nihon Medi-Physics Co, Ltd Expert Advisory Committee, AIM Specialty Health PURPOSE

Amino acid transport is upregulated in breast carcinoma. Anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) is a synthetic amino acid analog positron emission tomography (PET) radiotracer which is transported primarily via system ASCT2 and LAT1 amino acid transporters. The purpose of this exploratory study is to characterize anti-3-[18F] FACBC uptake in benign and malignant breast lesions.

METHOD AND MATERIALS

Four women with histologic confirmation of breast carcinoma or about to undergo biopsy for suspected breast carcinoma not currently undergoing therapy underwent 45 minute dynamic anti-3-[18F]FACBC PET-CT. Standardized uptake values (SUVs) within malignant and benign breast lesions as well as the contra-lateral normal breast were recorded at 5-8mins, 17-21mins, 29-32mins and 41-44mins time frames. Findings were validated by histologic and imaging correlation. T-tests were used to examine the significance of difference in the mean SUVmax of benign to malignant lesions as well as to normal breast tissue.

RESULTS Average age ±SD was 64.25 ± 11.2 years. Average dose ±SD of anti-3-[18F] FACBC injected was 9.8mci ±0.3. There were 7 breast lesions characterized in 4 patients; 3 benign and 4 malignant (Figure 1A and B). Malignant lesions had significantly higher SUVmax compared to benign lesions and normal contra-lateral breast tissue at all time points (Figure 1C). There was no significant difference in the mean SUVmax of benign breast lesions and normal contra-lateral breast at any time point (Figure 1).

CONCLUSION

Anti-3-[18F] FACBC shows promise in delineating malignant from benign breast lesions and normal breast tissue. Our result may guide the design of larger studies examining its utility in breast cancer detection, staging and restaging.

CLINICAL RELEVANCE/APPLICATION

Anti-3-[18F] FACBC characterization of amino acid transport upregulation may be useful for the diagnosis of breast cancer and to differentiate malignant from benign lesions.

SSA12-04 Diagnostic Value of Diffusion-weighted Imaging in a Simultaneous 18F-FDG PET/MRI Protocol for Whole-body Staging of Female Patients with Pelvic Malignancies Johannes Grueneisen (Presenter): Nothing to Disclose , Benedikt Michael Schaarschmidt MD : Nothing to Disclose , Karsten J. Beiderwellen MD : Nothing to Disclose , Martin Heubner : Nothing to Disclose , Michael Forsting MD : Nothing to Disclose , Thomas C. Lauenstein MD : Nothing to Disclose , Lale Umutlu MD : Consultant, Bayer AG PURPOSE

To evaluate the diagnostic benefit of diffusion-weighted imaging (DWI) in a simultaneous 18F-FDG PET/MRI protocol for whole-body staging of patients with primary or recurrent malignancies of the female pelvis.

METHOD AND MATERIALS

67 patients with primary or a suspected recurrence of a pelvic malignancy were included in our study. All patients underwent whole-body 18F-FDG PET/MRI (Biograph mMR, Siemens) including DWI. Two radiologists separately evaluated the 18F-FDG PET/MRI datasets without DWI followed by a second reading including DWI. After assessment of (1) overall lesion detection, all lesions considered as malignant were evaluated concerning (2) lesion conspicuity (4-point ordinal scale) and (3) diagnostic confidence (3-point ordinal scale). In a second session, the lesion-to-background contrast and diagnostic confidence for PET and DWI was assessed qualitatively. Wilcoxon signed-rank test was applied to assess statistical significance.

RESULTS A total of 136 primary and recurrent tumor lesions were detected in 58 of the 67 patients. 18F-FDG PET/MRI including DWI revealed an insignificantly minimal higher lesion conspicuity (PET/MRI + DWI: 3,85 ± 0,38; PET/MRI - DWI: 3,88 ± 0,37) and diagnostic confidence (PET/MRI: 2,71 ± 0,57 DWI: 2,77 ± 0,50) in comparison to PET/MRI without DWI. Furthermore, the lesion-to-background contrast revealed significantly higher values for PET (3,82 ± 0,43) in comparison to DWI (3,57 ± 0,80) with a significantly higher diagnostic confidence (PET: 2,70 ± 0,58; DWI: 2,51 ± 0,68) for malignancy (p < 0,01).

CONCLUSION

DWI in PET / MRI does not provide a diagnostic benefit for whole-body staging of female patients with pelvic malignancies. Regarding the advantages of PET in comparison to DWI in the delineation and characterization of tumor lesions, DWI should be questioned as an integral part of PET / MRI protocols for whole-body tumor staging.

CLINICAL RELEVANCE/APPLICATION

The omission of DWI in whole-body tumor staging of pelvic malignancies may lead to a significant reduction of examination times, thus increasing patient comfort without a relevant decrease in diagnostic competence.

SSA12-05 Pharmacodynamic Imaging of Estrogen Receptor Guides Dosing of Fulvestrant Pedram Heidari MD (Presenter): Nothing to Disclose , Francis Deng BA : Nothing to Disclose , Shadi A. Esfahani MD, MPH : Nothing to Disclose , Alicia Leece : Nothing to Disclose , Umar Mahmood MD, PhD : Research Grant, Sabik Medical Inc PURPOSE Fulvestrant, an estrogen receptor degrader, is now widely used in management of breast cancer (BrCa). Currently, there are no methods to optimize treatment dosing of fulvestrant. This study assesses the utility of pharmacodynamic imaging using 16Α-[18F]-fluoroestradiol (18F-FES) in dose optimization of fulvestrant in a preclinical model of ER+ BrCa.

METHOD AND MATERIALS MCF7 cells (ER+) were incubated with different doses of fulvestrant for 24 h. Retention of 18F-FES was measured and compared to ERΑ protein expression (ELISA) and ESR1 mRNA transcription (qPCR). MCF7 tumors were grown in ovariectomized nude mice. The mice were randomly assigned to vehicle, low- (0.05mg), medium- (0.45mg) or high-dose (5mg) treatment groups (n=5-7). Two days after fulvestrant treatment, PET/CT was performed using 18F-FES and 18F-FDG. ER expression was assayed by immunohistochemistry (IHC), ELISA, and qPCR on xenografts. Tumor proliferation was assessed using Ki-67 IHC.

RESULTS In vitro, fulvestrant was equipotent at reducing 18F-FES uptake as ER protein expression, despite stimulating mRNA transcription severalfold. In xenografts, ER expression significantly decreased with fulvestrant treatment in a dose-dependent manner both in ELISA of tumor lysates and IHC staining, despite similar mRNA expression. No difference in Ki-67 staining was observed among the treatment groups. We observed a significant dose-dependent reduction of 18F-FES PET SUVmean with fulvestrant treatment, but no significant difference among the treatment groups in 18F-FDG PET parameters.

CONCLUSION We demonstrated that 18F-FES uptake mirrors the dose-dependent changes in functional ER expression with fulvestrant treatment which precedes the changes in tumor metabolism and proliferation. Pharmacodynamic imaging of estrogen receptor may be useful for tracking early efficacy of ER degradation and guiding ER-targeted therapy dosing in BrCa patients.

CLINICAL RELEVANCE/APPLICATION precise anti-ER dosing in individual patients using pharmacodynamic imaging of ER may improve therapy response

SSA12-06 18F-Fluoroethylcholine PET/CT in Endometrial and Cervical Tumors: First Experience and Comparison with 18F-FDG PET/CT and DW-MRI Tara Diane Barwick MBChB (Presenter): Nothing to Disclose , Nishat Bharwani MBBS, FRCR : Nothing to Disclose , Sameer Khan MBBS : Nothing to Disclose , Marc Eric Miquel PhD : Nothing to Disclose , Andrea Grace Rockall MRCP, FRCR : Nothing to Disclose PURPOSE 1.Prospective evaluation of 18F-fluoroethylcholine (FEC) PET/CT in the detection of cervical and endometrial tumors 2.Degree of correlation with 18F-FDG PET/CT and whole tumor ADCmean (mean apparent diffusion co-efficient) on diffusion weighted (DW-) MRI

METHOD AND MATERIALS Sub-group analysis of patients prospectively recruited to the multi-centre MAPPING study (Eudra CT:2011-001290-78). Preliminary findings of 15 patients with surgically staged endometrial (n=6,FIGO stage 2-4B) and cervical cancer (n=9,FIGO stage 1B1-2B). The endometrial tumors were 5 endometrioid adenocarcinomas (grades 1 and 2) and 1 clear cell carcinoma. The cervical tumors were 4 squamous cell carcinomas (SCC), 3 adenosquamous tumors, 1 adenocarcinoma and 1 undifferentiated tumor. Each patient underwent DW-MRI, FDG and FEC PET/CT. The PET/CT studies were performed on consecutive days. The time interval between DW-MRI and first PET/CT was 0-17 days. 4 cervical cancer cases (all SCC) were excluded as the primary tumor was excised at cone biopsy leaving 11 for analysis. The correlation between tumor grade, FDG SUVmax, FEC SUVmax and ADCmean of the primary tumor were determined.

RESULTS There were no adverse effects documented following the FEC administration. The primary tumor was visualized in 10/11 cases on FEC PET/CT and on all FDG PET/CT and DW-MRI studies. Mean SUVmax FEC (7.2±3.8) was significantly lower than mean SUVmax FDG (16.6±10.7;p=0.005) but there was a positive correlation between values (r=0.78). There was no correlation between ADCmean and FEC or FDG SUVmax (r=-0.35 and -0.24 respectively). When comparing high (G3) with low grade (G1+2) tumors there was a significant difference in whole tumor ADCmean (p=0.004) but no significant difference demonstrated in FEC or FDG SUVmax (p=0.25 & 0.28 respectively). 0.28 respectively).

CONCLUSION FDG PET/CT has been disappointing in staging early endometrial and cervical tumors. We have evaluated 18F-FEC, an alternative tracer which is effective in prostate cancer staging. Preliminary results show imaging of endometrial and cervical cancers with 18F-FEC is feasible. There is positive correlation with FDG uptake but in general tumor FEC SUVmax is lower than FDG SUVmax.

CLINICAL RELEVANCE/APPLICATION Preliminary results suggest that imaging of primary endometrial and cervical cancers with 18F-fluoroethylcholine PET/CT is feasible. Further evaluation is now required to assess staging accuracy.

SSA12-07 A Novel PET Probe for Imaging HER3 Receptor Status Eric Wehrenberg-Klee MD (Presenter): Nothing to Disclose , Nafize Selcan Turker PhD : Nothing to Disclose , Pedram Heidari MD : Nothing to Disclose , Umar Mahmood MD, PhD : Research Grant, Sabik Medical Inc , Bryan Chang : Nothing to Disclose PURPOSE HER3 is a surface receptor tyrosine kinase that plays an important role in pro-oncogenic signaling pathways. The receptor is expressed at low-copy number, which is potentially limiting for PET probe development. We developed an antibody-based PET probe specific for HER3, characterized it in vitro, and successfully image HER3 expressing xenografts. We demonstrate that the ability to image this low-expression surface protein is time-dependent, and is related to internalization of receptor-probe complex

METHOD AND MATERIALS 64Cu-DOTA-HER3 F(ab')2 was prepared from whole HER3 monoclonal antibody with F(ab)'2 fragmentation and chelator conjugation, and its affinity for HER3 assessed using radio-labeled binding studies. HER3 surface-expression on multiple cell lines was confirmed using fluorescent-activated cell sorting (FACS). Probe internalization kinetics were determined by conducting cell uptake studies at both 4°C and 37°C. Results of cell uptake studies were correlated with geometric mean FITC signal obtained from FACS. In vivo PET-CT imaging with 64Cu-DOTA-HER3 F(ab')2 was conducted using mouse xenografts of MDA-MB 468 and HCC 70 tumors (n=3 for both groups).

RESULTS The HER3 PET probe demonstrates a HER3 Kd of 6.8 nM. FACS confirmed HER3 expression of approximately 200 receptors per cell across multiple lines. Cell uptake studies demonstrate counts/minute/cell of 0.28, 0.45, 0.82 for MCF-7, HCC-70, and MDA-MB-468 cells, respectively after 1 hour. Time course studies demonstrate linear increase of HER3 probe uptake over time at 37°C but not at 4°C that correlates with findings on FACS. In vivo imaging with the HER3 PET Probe of MDA-MB-468 and HCC70 tumor xenografts demonstrate SUVs of 0.35 and 0.59, with TBRs of 6.0 and 11.4 respectively.

CONCLUSION We have developed a HER3 specific PET probe, and demonstrate successful in vivo imaging of HER3 expressing xenografts. We demonstrate that imaging of a low-expression surface protein is possible, and is dependent upon internalization of the receptor-probe complex. These findings have relevance for the development of PET probes for imaging of low-expression receptors of clinical interest.

CLINICAL RELEVANCE/APPLICATION The developed HER3 PET probe has utility for measuring HER3 expression levels on cancers, which is thought to be a primary mediator of resistance to HER2 inhibition.

SSA12-08 Breast Cancer Follow Up: Comparison of Whole-body Hybrid PET/MR and PET/CT Imaging: Initial Experience Onofrio Antonio Catalano MD (Presenter): Nothing to Disclose , Bruce R. Rosen MD, PhD : Research Consultant, Siemens AG , Dushyant V. Sahani MD : Research Grant, General Electric Company , Carlo Iannace MD : Nothing to Disclose , Angelo Luongo : Nothing to Disclose , Marco Catalano : Nothing to Disclose , Mark Vangel PhD : Nothing to Disclose , Marco Aiello : Nothing to Disclose , Emanuele Nicolai : Nothing to Disclose , Alexander Ramos Guimaraes MD, PhD : Speakers Bureau, Siemens AG Expert Witness, Rice, Dolan, Kershaw , Andrea Soricelli MD : Nothing to Disclose , Marco Salvatore MD : Nothing to Disclose PURPOSE

To compare the diagnostic performance of whole-body PET/MR with PET/CT in patients followed up for treated breast cancer

METHOD AND MATERIALS 76 consecutive patients with treated breast cancer underwent whole-body FDG-PET/CT (Gemini TF, Philips) and same day FDG-PET/MR (Biograph mMR, Siemens). Two readers independently evaluated PET/CT and PET/MR studies for local recurrence as well as metastases according to published imaging criteria

RESULTS 5 patients were excluded due to data corruption, 1 because of study interruption. MRPET quality was adequate in the remaining 70 patients. PET/MR and PET/CT were concordant in 59 patients, ruling out recurrent disease/metastases in 24 and disclosing recurrent disease or metastases in 35. PET/MR and PET/CT were disease/metastases in 24 and disclosing recurrent disease or metastases in 35. PET/MR and PET/CT were discordant in: in 4 PET/MR disclosed metastases not detected at PET/CT, in 1 PET/MR demonstrated local recurrence not seen on PET/CT. In 5 PET/MR correctly interpreted benign findings (sarcoidosis in 1, benign pelvic disease in 1, benign bony lesions in 3) confused with metastases on PET/CT. PET/CT demonstrated sclerotic bony lesion in 1 that was missed at PET/MR, however comparison with prior CT dating back to 4 years ago showed stability and therefore it was interpreted as a benign lesion

CONCLUSION PET/MR imaging of treated breast cancer is feasible and provides diagnostic image quality in the assessment of possible local recurrent disease as well as metastases. PET/MR did not under-stage any patient when compared to PET/CT and provided the correct diagnosis for all 11 discordant cases (95% binomial upper confidence limit 0.24)

CLINICAL RELEVANCE/APPLICATION

PET/MR might represent an innovative and valid tool for accurate follow up of breast cancer patients

SSA12-09 Multimodal Magnetic Resonance and Near Infrared-Fluorescent Imaging of Intraperitoneal Ovarian Cancer Using a Dual-Mode, Dual-Gadolinium Liposomal Contrast Agent Murali Ravoori : Nothing to Disclose , Sheela Singh : Nothing to Disclose , Rohan Bhavane PhD : Nothing to Disclose , Bahman Anvari PhD : Nothing to Disclose , Ananth Annapragada PhD : Stockholder, Marval Pharma Ltd Stockholder, Alzeca Biosciences LLC Stockholder, Sensulin LLC Stockholder, Abbott Laboratories Stockholder, Johnson & Johnson , Vikas Kundra MD, PhD (Presenter): License agreement, Introgen Therapeutics Inc , James Bankson PhD : Nothing to Disclose PURPOSE

To assess whether a dual-mode, dual-Gadolinium (DM-Dual Gd) liposomal contrast agent can be used to visualize intraperitoneal ovarian tumors by multimodal magnetic resonance (MR) and near infra-red (NIR) imaging.

METHOD AND MATERIALS

DM-Dual Gd was manufactured based on the Dual Gd format for MR, with gadolinium molecules on the surface and within the lumen of the liposome to increase relaxivity, and the NIR agent indocyanine green (ICG) within the lumen. Phosphorus (P) and Gd content were measured by ICP-AES. Female nude mice bearing intraperitoneal Hey A8 human ovarian cancer tumors were injected IV with or without DM-Dual Gd (n=6). Two days later, the animals were imaged by T1-weighted MR. Afterwards, NIR imaging of open abdomen and excised tumors/organs was performed. Signal to noise ratio (SNR) was used to compare tumor enhancement by MR and radiant efficiency to compare tumor signal by NIR imaging. For robustness, experiments were repeated using a second human ovarian cancer (OVCAR-3) model.

RESULTS Gd content was 60.34 mM and P content was 29.44 mM resulting in a Gd/P ratio of 2.05 per particle. On T1-weighted MR images, intraperitoneal ovarian tumors (HeyA8 or OVCAR3) enhanced compared to control tumors two days after DM-dual Gd injection (SNR, p<.05). As seen in the laporatomy and excised tumors views, HeyA8 or OVCAR3 tumors from animals injected with DM-dual Gd had increased fluorescence compared to control tumors (p<.05).

CONCLUSION DM-Dual Gd can be used to visualize intraperitoneal ovarian tumors by MR and NIR imaging in pre-clinical intraperitoneal ovarian cancer mouse models.

CLINICAL RELEVANCE/APPLICATION

Nearly 75% of patients with ovarian cancer present with intraperitoneal disease; and, the degree of cytoreduction at surgery is one of the most important factors for prognosis. Current imaging is limited in detecting peritoneal disease and surgery relies on the naked eye to identify nodules for resection. The current findings suggest clinical potential for using a single injection of a single nanoparticle (DM-Dual Gd) to localize tumor by MR for pre-surgical planning and by NIR at the time of surgery for resection.

MIS-SUA Molecular Imaging Sunday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Sun, Nov 30 12:30 PM - 1:00 PM Location: S503AB

Participants Moderator Chun Yuan PhD : Research Grant, Koninklijke Philips NV Consultant, Bristol-Myers Squibb Company Consultant, Koninklijke Chun Yuan PhD : Research Grant, Koninklijke Philips NV Consultant, Bristol-Myers Squibb Company Consultant, Koninklijke Philips NV Moderator Markus Schwaiger MD : Research Grant, Siemens AG

Sub-Events

MIS115 Quantifying Progression and Regression of Atherosclerosis in ApoE-/- Mice Using Gadospin F at 7T MRI: Comparison of Volumetric Method and T1 Relaxivity to en Face Measurements (Station #7) Caroline Jung (Presenter): Nothing to Disclose , Sabine Christiansen : Nothing to Disclose , Michael Gerhard Kaul : Nothing to Disclose , Markus Heine : Nothing to Disclose , Harald Ittrich MD : Nothing to Disclose , Gerhard B. Adam MD : Nothing to Disclose PURPOSE

The aim of this study was to quantify atherosclerotic plaque by volumetric assessment and by determining T1 Relaxivity at 7T MRI using Gadospin F (GDF) in comparison to en face measurements.

METHOD AND MATERIALS Mice (n=5 for each group) were set on high fat diet (HFD) at 9 weeks of age. In-vivo MRI of the aortic vessel wall was performed at 9, 13, 17 and 21 weeks after commencement of the HFD. Therapy group was reswitched to normal rodent diet 13 weeks after starting HFD and monitored by MRI for 12 weeks. ApoE-/- and control mice were imaged before and two hours after i.v. injection of GDF (dosage: 100 µmol/kg) at a small animal MRI at 7T (Clinscan, Bruker). MRI was performed using a 3D Inversion Recovery Gradient echo MR sequence (TR/TE 650/2 ms, TI 250ms; FA 20°; NSA 6, matrix 196 x 196, 64 slices, slice thickness 180µm; TA 9min, eff. voxel resolution (180 µm)3 in transverse orientation covering the thoracic aorta. In same slice orientation T1 Mapping was performed using Saturation Recovery sequences. Subsequently, mice were killed for en face preparation. MR image analyses were performed using ImageJ (V. 1.44p, NIH, USA). Total plaque volume (TPV), total plaque volume relative to the examined area of the aorta (rTPV) and T1 Relaxivity were estimated. Pearson correlation between MRI and en face measurements was analysed.

RESULTS MRI and en face analyses showed an exponential increase of TPV, rTPV and T1 relaxivity over time, which showed a slower and linear increase for therapy group. A good correlation (r=0.74; p<0.001) for TPV between MRI and en face measurements was observed which was even stronger estimating the rTPV (r=0.89; p<0.001). A correlation of r=0.71 (p<0.001) was achieved between T1 relaxivity and TPV en face measurements, while only a correlation of r=0.57 (p<0.01) was found between rTPV in en face measurements and T1 relaxivity. In control mice no plaque volume was observed. A moderate but not significant correlation was found for body weight and cholesterol and triglyceride level (r>0.7 and r>0.8, respectively).

CONCLUSION

GDF-enhanced MRI showed a moderate to strong correlation between measured plaque volume and T1 Realxivity in vivo and typical en face measurements ex vivo.

CLINICAL RELEVANCE/APPLICATION

GDF-enhanced in vivo MRI is a powerful noninvasive imaging technique allowing reliable estimation of plaque burden, monitoring of disease progression and evaluation of therapy response in preclinical studies.

MIS116 Ultrasound-targeted Microbubble Load with Copper for Myocardial Infarction: Assessment with Echocardiography and 3.0T Magnetic Resonance Imaging in Rhesus Monkey [ MI Scavenger Hunt! ] (Station #8) Lizhi Zhang MD (Presenter): Nothing to Disclose , Pengfei Han : Nothing to Disclose , Chunchao Xia : Nothing to Disclose PURPOSE

Copper (Cu) has the ability of stimulating microvessel formation by regulating VEGF expression after myocardial infarction (MI). The aim of this study is to prospectively determine the effects of ultrasound-targeted microbubble destruction (UTMD) loaded with Cu intervening MI in the rhesus monkey, and to quantitatively evaluate the cardiac function and myocardial angiogenesis after treatment with echocardiography and 3.0T MRI scanner.

METHOD AND MATERIALS The institutional animal care and use committee approved this study. Fifteen MI models were established by ligation the left anterior descending artery of coronary artery. MI was successfully induced in 15 rhesus monkeys (2-year-old) by ligation the left coronary artery. They were randomly assigned into three groups (n=5 in each group): UTMD loaded Cu group, microbubble loaded Cu without destruction group, and control group. Echocardiography and MRI was used to trace the Cu and measure the perfusion, infracted region, and LV ejection fraction. HandE, TTC stains and immunohistochemistry were used to assess the infracted region and microvessel density (MVD). One way ANOVA test was used to determine significantly differences between animal groups. Bonferroni correction was used to adjust p values for multiple comparisons.

RESULTS After therapy, the infarcted regions in the UTMD loaded Cu group significantly reduced at perfusion and delayed-enhancement imaging (p<0.05), and ejection fractions increased (p<0.05) when compared with control and Cu without destruction groups. In contrast, the infarcted regions and ejection fractions deteriorated in control group. Histopathologic findings and MVD in the UTMD loaded Cu group were better than the results in others groups (p=0.01).

CONCLUSION

Ultrasound-targeted microbubble can effectively deliver Cu to the infracted region, which significantly improved cardiac functions, reduced infarcted regions, and stimulated angiogenesis. MR imaging may be helpful to dynamically monitor and assess the therapeutic effects in vivo.

CLINICAL RELEVANCE/APPLICATION

Copper (Cu) has the ability of stimulating microvessel formation by regulating VEGF expression after myocardial infarction (MI). Ultrasound-targeted microbubble can effectively deliver Cu to the infracted region, which significantly improved cardiac functions, reduced infarcted regions, and stimulated angiogenesis. Our study provides a novel way in the therapy of myocardial infarction.

MIS117 Preliminary Results: Functional and Morphological Evaluation of Hand Microcirculation of the Hand in Patients with Symptoms of Upper Extremity Ischemia by Means of a 2D Optical Imaging System (Station #9) Jan Neumann MD (Presenter): Nothing to Disclose , Alexander Zimmermann : Nothing to Disclose , Christoph Schmaderer : Nothing to Disclose , Moritz Wildgruber MD, PhD : Nothing to Disclose , Ernst J. Rummeny MD : Nothing to Disclose , Reinhard Meier MD, PhD : Nothing to Disclose PURPOSE

The aim of this study was to investigate an Indocyanine Green (ICG)-enhanced optical imaging (OI) system to differentiate between haemodynamic relevant stenosis looking at the microcirculation of the hand in patients with symptoms of upper extremity ischemia and volunteers.

METHOD AND MATERIALS 3 female Patients (mean age = 42.3) with clinical suspicion of upper extremity peripheral artery disease including claudication, rest pain, or tissue loss and 10 healthy volunteers were examined with a clinically new available ICG-enhanced optical imaging system (mivenion GmbH, Germany). The microcirculation of both hands was graded objectively by three independent radiologists on a 3-point-ordinate scale (0: normal blood flow, 1: mild, 2: severe alteration of microcirculation). Results were correlated with CT, MRI or angiography as standard of reference.

RESULTS All patients showed in OI an alteration of microcirculation of the affected hand in comparison to the healthy contralateral hand and in comparison to the healthy volunteers. CT, MRI or angiography as standard of reference confirmed a stenosis of upper extremeties arteries, dialysis (AV) shunt malfunction or vascular anomalies. The differences were significant between the patient group compared to the control group (p<0.05).

CONCLUSION Our preliminary data shows, that optical imaging allows to differentiate between haemodynamic relevant stenosis looking at the microcirculation of the hand in patients with symptoms of upper extremity ischemia. OI might be of substantial added value to clinical examination due to its non-invasiveness, low costs and easy availability.

CLINICAL RELEVANCE/APPLICATION

OI is a fast, inexpensive, non-invasive and non-ionizing imaging modality which has potential to be helpful for characterization of the cutaneous microvascularization in patients with symptoms of upper extremity ischemia.

MIS118 Performance of Whole-body PET/MR and PET/CT in Evaluating Bony Metastases in Breast Cancer Patients (Station #10) Onofrio Antonio Catalano MD (Presenter): Nothing to Disclose , Bruce R. Rosen MD, PhD : Research Consultant, Siemens AG , Carlo Iannace MD : Nothing to Disclose , Emanuele Nicolai : Nothing to Disclose , Angelo Luongo : Nothing to Disclose , Marco Catalano : Nothing to Disclose , Dushyant V. Sahani MD : Research Grant, General Electric Company , Leon Jonathan Menezes FRCR : Stockholder, General Electric Company Research Grant, Advanced Accelerator Applications SA Research Grant, Eli Lilly and Company , Mark Vangel PhD : Nothing to Disclose , Leonardo Pace : Nothing to Disclose , Andrea Soricelli MD : Nothing to Disclose , Marco Salvatore MD : Nothing to Disclose PURPOSE

To compare the diagnostic performance of whole-body FDG-PET/MR with same day FDG-PET/CT in the detection of bony metastases in patients with breast cancer (BC).

METHOD AND MATERIALS 144 consecutive patients with BC underwent whole-body FDG-PET/CT (Gemini TF, Philips) and same day FDG-PET/MR (Biograph mMR, Siemens). PET/CT and PET/MR studies were independently evaluated by two FDG-PET/MR (Biograph mMR, Siemens). PET/CT and PET/MR studies were independently evaluated by two readers. Attenuation correction of PET/MR was performed with Dixon sequences. Accepted morphologic and nuclear medicine criteria were used to assess for bony metastases. Patients were excluded in the case of innumerable metastases or of benign lesions. In the case of numerous but still countable lesions, they all were counted. However only of the 5 most FDG-avid lesions had the SUV measured.

RESULTS PET/MR quality was deemed adequate in 142/144 patients. 5 were excluded due to innumerable metastases and 5 because of the benign nature. Bony metastases were found in 22/132 patients on PET/MR and in 20/132 patients on PET/CT. A total of 132 metastases were found in 22 patients. In 9/22 patients PET/MR and PET/CT detected the same number of lesions, in 13/22 PET/MR disclosed more metastases than PET/CT. PET/MR detected 132 metastases: 70/132 both on PET and MR, 55/132 on MR only, 7/132 on PET only. Average SUV 6.88, SD±5.09. PET/CT demonstrated 75 metastases: 44/75 both on PET and CT, 8/75 on CT only, 23/75 on PET only. Average SUV 5.84, SD±3.84.

CONCLUSION

FDG-PET/MR demonstrated more numerous metastases per patient and metastases in more patients than same day FDG-PET/CT.

CLINICAL RELEVANCE/APPLICATION

PET/MR might represent a very promising and accurate technique for detection of bony metastases in breast cancer patients.

MIS-SUB Molecular Imaging Sunday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Sun, Nov 30 1:00 PM - 1:30 PM Location: S503AB

Sub-Events MIS119 Visceral Obesity Assessed by 1H-MRS Predicts Cardiovascular Events in Type 2 Diabetic Patients (Station #7) Ettore Squillaci MD (Presenter): Nothing to Disclose , Francesca Bolacchi : Nothing to Disclose , Marco Antonicoli : Nothing to Disclose , Simone Altobelli : Nothing to Disclose , Giovanni Simonetti MD : Nothing to Disclose PURPOSE

Cardiovascular disease is the leading cause of death among patients with type 2 diabetes. Although there is emerging evidence that excess visceral fat is associated with a cluster of cardiometabolic abnormalities in these patients, the impact of visceral obesity evaluated by a gold-standard method on future outcomes has not been studied. We aimed to investigate whether visceral obesity assessed by 1H-MRS was able to predict cardiovascular events in type 2 diabetic patients.

METHOD AND MATERIALS We studied 38 type 2 diabetic patients [age 63 ± 7 years; body mass index (BMI) 27 ± 5.2 kg/m(2). Visceral abdominal fat was analysed by single voxel magnetic resonance spectroscopy (MRS). The MRS lipid spectrum was analysed and a lipid polyunsaturation index (PUI) was calculated. Fifteen healthy subjects were enrolled as controls. Cardiovascular events including acute myocardial infarction, angina, arrhythmia, uncontrolled blood pressure, stroke and cardiac failure were recorded during 24 months.

RESULTS

Cardiovascular events were 3-fold higher in patients with higher PUI index. The Kaplan-Meier analysis indicated that patients with a high PUI index had shorter cardiovascular event-free time than those a normal PUI values (P = 0.031). In the univariate Cox analysis, PUI was associated with higher risk of cardiovascular events (hazard ratio = 3.4; 95% confidence interval = 1.1-10.5; P = 0.03). The prognostic power of PUI for cardiovascular events remained significant after adjustments for sex, age, diabetes, previous cardiovascular disease, smoking, sedentary lifestyle, BMI, GFR, hypertension, dyslipidemia and inflammation.

CONCLUSION

Visceral fat as analysed by 1H-MRS is a valuable tool in predicting cardiovascular events in diabetic type 2 patients.

CLINICAL RELEVANCE/APPLICATION Visceral fat 1H-MRS provides biomarkers that predict cardiovascular events in diabetic type 2 patients. Visceral fat 1H-MRS provides biomarkers that predict cardiovascular events in diabetic type 2 patients.

MIS120 Multiparametric Functional MRI for Assessment of Acute Renal Allograft Rejection in Mice—Comparison with Renal Histology (Station #8) Bennet Johannes Ulrich Hensen (Presenter): Nothing to Disclose , Song Rong MD : Nothing to Disclose , Marcel Gutberlet DiplPhys : Nothing to Disclose , Matti Peperhove MD : Nothing to Disclose , Susanne Tewes MD : Nothing to Disclose , Martin Meier PhD : Nothing to Disclose , Sibylle von Vietinghoff : Nothing to Disclose , Michael Mengel : Nothing to Disclose , Frank K. Wacker MD : Research Grant, Siemens AG Research Grant, Pro Medicus Limited , Dagmar Hartung MD : Nothing to Disclose , Faikah Gueler MD : Nothing to Disclose , Katja Hueper : Nothing to Disclose PURPOSE

To investigate whether multiparametric MRI allows detection of acute renal allograft rejection (AR) and to compare MRI parameters with renal histopathology.

METHOD AND MATERIALS AR was induced by allogenic kidney transplantation (ktx) of C57Bl/6-kidneys to Balb/c-mice (n=6). Animals after isogenic ktx (C57Bl/6-kidneys to C57Bl/6-mice) served as controls. Mice were examined 3 weeks after ktx using a 7T MRI. The multiparametric MRI protocol consisted of perfusion imaging (FAIR EPI ASL), T1- (IR EPI) and T2-mapping (multi echo TSE) and diffusion weighted imaging (7 b-values=0-700 s/mm2). Animals were sacrificed after the MRI. Renal histology (Banff) and macrophage and T-cell infiltration (immunohistochemistryandFACS) were examined. Differences between groups were evaluated using unpaired t-tests and MRI parameters were compared with amount and composition of cell infiltrates. Values are given as mean±SEM.

RESULTS Animals after allogenic ktx developed an acute T-cell-mediated rejection (Banff IIB/III), whereas renal histology after isogenic ktx was unremarkable. Renal perfusion was impaired in animals with allogenic compared to isogenic ktx (56±7 vs 293±44 ml/(min*100g); p<0.001). After allogenic ktx T1- and T2-times of the outer stripe of the outer medulla were increased compared to isogenic ktx (T1: 1938±53 ms vs 1350±27 ms, p<0.001; T2: 60.1±1.9 ms vs 45.7±1.1 ms, p<0.001). ADC-values were significantly lower in animals with AR (1.38±0.14*10-3 mm2/s) compared to controls (1.82±0.05*10-3 mm2/s, p<0.05). Correspondingly, in allogenic animals infiltration of macrophages (score 3.8±0.2 vs 1.1±0.2; p<0.001) and T-cells (score 3.4±0.2 vs. 1.0±0; p<0.001) was significantly more pronounced than in controls. FACS-analysis revealed an increased percentage of infiltrating T-cells (38.8±4.0% vs 5.5±2.2%; p<0.001).

CONCLUSION

Multiparametric functional MRI allows detection of acute renal AR. AR was characterized by renal perfusion impairment, increase of T1- and T2-values, interpreted as tissue edema, and reduced ADC due to cellular infiltration. These changes correspond well to renal histology and amount of infiltrating cells.

CLINICAL RELEVANCE/APPLICATION

Multiparametric functional MRI allows non-invasive diagnosis of acute renal allograft rejection. It may additionally help to differentiate renal allograft pathologies such as acute rejection (allogenic ktx) and ischemia/reperfusion injury (isogenic ktx) and to facilitate therapy decisions in an early state.

MIS121 Preoperative Evaluation of Future Remnant Liver Function by the Coefficient Variation of Contrast Enhanced Ratio in Hepatocellular Image (Station #9) Shigeru Matsushima PhD (Presenter): Nothing to Disclose , Yozo Sato MD, PhD : Nothing to Disclose , Hidekazu Yamaura MD : Nothing to Disclose , Mina Kato MD : Nothing to Disclose , Yasutomi Kinosada MD, PhD : Nothing to Disclose , Seiichi Era MD, PhD : Nothing to Disclose , Kazuya Takahashi BS : Nothing to Disclose , Yoshitaka Inaba MD : Nothing to Disclose PURPOSE Preoperative evaluation of future remnant liver (FRL) function is crucial in the determination of whether a patient can safely undergo liver resection. A more reliable index for estimating postoperative liver failure is ICG clearance of the future remnant liver (ICG-Krem). However, ICG-Krem assumes that uptake is homogeneous throughout the liver. Gadoxetic acid disodium is a newly developed MR contrast agent for hepatocellular imaging; we reported that the contrast enhance ratio in hepatocellular (CERH) imaging is a potentially useful method for heterogeneous liver function image by MRI. The purpose of this study is to evaluate of FRL function through the coefficient variation of CERH value (CvCERH).

METHOD AND MATERIALS 21 patients underwent surgery for tumor excision. All were found to have Child-Pugh class A disease. FRL function was evaluated by an increased international normalized ratio (INR) after postoperative five day that defined according to the grading system of the International Study Group of Liver Surgery. INR increased in the three patients. Hepatocellular images were obtained 20 minutes after an intravenous bolus injection of gadoxetic acid disodium. The CERH value was defined as the percentage of signal gain between the before contrast and hepatocellular images. The CERH images were constructed on the basis of the percentage of CERH values. In the whole liver and FRL, the CERH value measured the tumor-free liver parenchyma in the CERH images. The heterogeneous liver function was evaluated by CvCERH. We corrected ICG-Krem to heterogeneous liver function by CvCERH. The corrected ICG-Krem were defined as ICG-Krem ×(total liver CvCERH / FRL CvCERH). In the FRL, we examined a correlation between ICG-Krem, the corrected ICG-Krem and INR. We used the corrected ICG-Krem for detection of FRL liver function abnormality. used the corrected ICG-Krem for detection of FRL liver function abnormality.

RESULTS ICG-Krem and the corrected ICG-Krem correlated with INR (r=-0.52 and -0.53, p < 0.05). The corrected ICG-Krem was able to detect three patients with increased INR.

CONCLUSION The corrected ICG-Krem are able to add the heterogeneous liver function to ICG-Krem. The corrected ICG-Krem is useful parameters to evaluate FRL function more correctly.

CLINICAL RELEVANCE/APPLICATION The corrected ICG-Krem is a potentially useful method for preoperative evaluation of FRL function.

MIS122 Diagnostic Value of Simultaneous 18F-FDG PET / MRI for Whole-body Staging and Dedicated FIGO Staging of Patients with Primary Cervical Cancer: Preliminary Results (Station #10) Johannes Grueneisen (Presenter): Nothing to Disclose , Karsten J. Beiderwellen MD : Nothing to Disclose , Benedikt Michael Schaarschmidt MD : Nothing to Disclose , Antonia Schulze-Hagen : Nothing to Disclose , Michael Forsting MD : Nothing to Disclose , Thomas C. Lauenstein MD : Nothing to Disclose , Lale Umutlu MD : Consultant, Bayer AG PURPOSE

To evaluate the diagnostic value of integrated 18F-FDG PET / MRI for whole-body and dedicated FIGO staging of patients with primary cervical cancer

METHOD AND MATERIALS

21 patients with histopathologically confirmed cervical cancer underwent a whole body contrast-enhanced 18F-FDG PET / MRI (Biograph mMR, Siemens, Erlangen, Germany; 0.05 mmol/kg BW Dotarem, Guerbet) prior to therapy. Two radiologists separately evaluated the PET/MRI datasets, regarding local tumor spread of primary cervical cancer lesions as well as detection of nodal metastases and classified the results according to the FIGO staging system. Furthermore, SUV and ADC values of primary tumor lesions were analyzed and correlated with prognostic factors of cervical cancer / occurrence of metastasis, grading and FIGO stage. Mann-Whitney-U test was applied to assess statistical significance.

RESULTS According to histopathological / surgical findings, PET/MRI enabled correct classification of 19 of the 21 patients (90.5 %) according to FIGO staging. 2 of the 21 patients were misclassified as stage IB, while histopathology revealed locally and microscopic infiltrations of the surgical margins involving the vaginal cuff, resulting in stage 2A. All patients with lymph node metastases (n = 8) could be correctly identified based on PET/MRI. Quantitative assessments showed significantly higher SUVmax and lower ADC values for G3 in comparison to G1 and G2 tumors (p < 0.05). Additionally, higher SUVs and lower ADC values could be determined in nodal positive patients with a lack of statistical significance.

CONCLUSION

Our results underline the high potential of integrated PET/MRI for whole-body and dedicated FIGO staging of patients with primary cervical cancer, offering additional information on prognostic factors.

CLINICAL RELEVANCE/APPLICATION

Integrated PET/MRI may serve as a highly accurate diagnostic tool for dedicated FIGO staging of primary cervical cancer, providing additional prognostic information.

RC117 Molecular Imaging Beyond PET: MRI and Ultrasound/Photoacoustic Molecular Imaging

Refresher/Informatics US OI MR MI AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Sun, Nov 30 2:00 PM - 3:30 PM Location: S504CD

Participants Moderator Fabian Kiessling MD : Advisor, invivoContrast GmbH Co-owner, invivoContrast GmbH Advisor, Molecular Targeting Technologies, Inc Researcher, Bayer AG Researcher, Bracco Group Researcher, Merck KgaA Researcher, AstraZeneca PLC Researcher, Koninklijke Philips NV Researcher, FUJIFILM Holdings Corporation LEARNING OBJECTIVES 1) Attendees will learn the principles and applications of molecular imaging using ultrasound and photoacoustic imaging techniques. 2) Principles and applications of ultrasound molecular imaging will be reviewed. 3) Principles and applications of molecular imaging using photoacoustic imaging techniques will be presented. 4) Ultrasound guided drug delivery approaches will be reviewed. 5) At the end of this course, the attendees will understand the principles and potential clinical applications of ultrasound and optoacoustic molecular imaging as well as of ultrasound guided drug delivery.

Sub-Events RC117A Photoacoustic Imaging Stanislav Emelianov PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Understand the fundamental principles of photoacoustic imaging and major components of photoacoustic imaging system. 2) Knowing how photoacoustic images are formed and how to interpret photoacoustic images. 3) Understand how imaging contrast agents or imaging probes affect contrast, penetration depth and specificity in photoacoustic imaging. 4) Understand the ability of photoacoustic imaging system to visualize anatomical, functional and molecular properties of imaged tissue. 5) Identify the role of photoacoustic imaging in pre-clinical and clinical applications.

ABSTRACT Photoacoustic imaging or tomography - a non-ionizing, non-invasive, real-time imaging technique capable of visualizing optical absorption properties of tissue at reasonable depth and high spatial resolution, is a rapidly emerging biomedical and clinical imaging modality. Photoacoustic imaging is regarded for its ability to provide in-vivo morphological and functional information about the tissue. With the recent advent of targeted contrast agents, photoacoustics is capable of in-vivo molecular imaging, thus facilitating further molecular and cellular characterization of tissue. This presentation is designed to provide both a broad overview and a comprehensive understanding of photoacoustic imaging. With a brief historical introduction, we will examine the foundations of photoacoustics, including relevant governing equations, optical/acoustic properties of the tissues, laser-tissue interaction, system hardware and signal/image processing algorithms. Specifically, penetration depth and spatial/temporal resolution of photoacoustic imaging will be anlyzed. Integration of photoacoustic and ultrasound imaging systems will be discussed. Techniques to increase contrast and to differentiate various tissues in photoacoustic imaging will be presented. Furthermore, design, synthesis and optimization of imaging probes (typically, nanoconstructs or dyes) to enable molecular/cellular photoacoustic imaging will be presented. Special emphasis will be placed on contrast agents capable of multiplexed imaging, multi-modal imaging and image-guided therapy including drug delivery and release. The presentation will continue with an overview of several commercially available and clinically-relevant systems capable of photoacoustic imaging. Regulatory aspects of photoacoustic imaging systems and imaging contrast agents will be presented. Finally, current and potential biomedical and clinical applications of photoacoustics will be discussed.

RC117B Ultrasound Molecular Imaging Juergen Karl Willmann MD (Presenter): Research Consultant, Bracco Group Research Grant, Siemens AG Research Grant, Bracco Group LEARNING OBJECTIVES 1) To understand the acquisition and quantification principles of ultrasound molecular imaging. 2) To understand the characteristics and biodistribution of molecularly targeted ultrasound contrast agents. 3) To understand the role of ultrasound molecular imaging in preclinical and clinical applications.

ABSTRACT Ultrasound imaging is a widely available, relatively inexpensive, and real-time imaging modality that does not expose patients to radiation and which is the first-line imaging modality for assessment of many organs. Through the introduction of ultrasound contrast agents, the sensitivity and specificity of ultrasound for detection and characterization of focal lesions has been substantially improved. Recently, targeted contrast-enhanced ultrasound imaging (ultrasound molecular imaging) has gained great momentum in preclinical research by the introduction of ultrasound contrast agents that are targeted at molecular markers over-expressed on the vasculature of certain diseases. By combining the advantages of ultrasound with the ability to image molecular signatures of diseases, ultrasound molecular imaging has great potential as a highly sensitive and quantitative method that could be used for various clinical applications, including screening for early stage disease (such as cancer); characterization of focal lesions; quantitative monitoring of disease processes at the molecular level; assisting in image-guided procedures; and, confirming target expression for treatment planning and monitoring. In this refresher course the concepts of ultrasound molecular imaging are reviewed along with a discussion on current applications in preclinical and clinical research.

RC117C Sonographically-guided Drug Therapy Alexander L. Klibanov PhD (Presenter): Research Grant, Koninklijke Philips NV Co-founder, Targeson, Inc Stockholder, Targeson, Inc Institutional research collaboration, AstraZeneca PLC LEARNING OBJECTIVES 1) To identify the basic principles of ultrasound energy deposition as applied to molecular imaging and image-guided therapeutic interventions. 2) To combine the general physical principles of ultrasound-microbubble interaction, drug-carrier systems pharmacokinetics and ultrasound contrast imaging, apply this knowledge for the development of triggered delivery approaches in the setting of personalized medicine. 3) To understand advantages and disadvantages of ultrasound application in the potential image-guided intervention designs. 4) To identify and compare potential clinical applications of ultrasound-guided drug delivery.

ABSTRACT The reason of ultrasound use in drug delivery is to enhance drug action specifically in the area of disease. The design of such therapeutic intervention should assure that drug deposition or action enhancement take place only in the disease site, with the general goal to improve the therapeutic index. There are several approaches to ultrasound-assisted drug delivery. The first approach, closest to clinical practice, takes advantage of existing ultrasound contrast agents (intravenous gas microbubbles approved in US for cardiac imaging). When these bubbles are co-injected intravenously with the drugs, and ultrasound energy applied to the areas of disease, localized energy deposition leads to endothelium activation or transient "softening" of blood brain barrier (BBB). Drugs (including antibodies or liposomes) can thus transit BBB and achieve therapeutic action. Ultrasound imaging can be used for targeted focusing of ultrasound energy in the areas of disease. Second approach suggests attaching microbubbles to the drug or a drug carrier (including nucleic acid drugs). Microbubbles can be complexed with drug or gene carrier nanoparticles, so that local action of ultrasound would result in triggered drug release/deposit or transfection in the ultrasound-treated area. Third approach involves targeted microbubble design, as in ultrasound molecular imaging. Combination of targeted microbubbles with drug carrier makes possible unfocused ultrasound use, to act only in the areas of the target receptor expression, where microbubbles adhere and ultrasound energy is then deposited. Lately, formulation moved from microbubbles to smaller nanodroplet drug carriers, to reach interstitium, where drug release could take place upon ultrasound treatment. Overall, combination of ultrasound imaging, including contrast (molecular) imaging, focused ultrasound, and drug carrier systems will lead to novel image-guided therapies, especially applicable in the era of personalized medicine.

RC117D Magnetic Resonance Molecular Imaging Moritz Florian Kircher MD, PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

ABSTRACT The field of molecular MRI has exploded in the last decade, with hundreds of different concepts and probe designs developed and tested in vitro and in vivo. This talk will attempt at giving a structured overview over this vast arsenal of potentially useful approaches by focusing on those that have the highest potential for clinical translation. The approaches will be grouped into 6 major categories and their principles explained and illustrated with key examples: 1) Multimodal nanoparticles; 2) Activatable MRI probes; 3) Targeted superparamagnetic iron oxide nanoparticles; 4) non-targeted superparamagnetic iron oxide nanoparticles; 5) MRI-based Radiogenomics; and 6) Hyperpolarized magnetic resonance spectroscopic imaging.

RC118 Global Cancer Imaging—Insights from Overseas

Refresher/Informatics OI MR MI GU AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Sun, Nov 30 2:00 PM - 3:30 PM Location: S502AB

Sub-Events RC118A Functional and Molecular Imaging at Oxford University Fergus Vincent Gleeson MBBS (Presenter): Alliance Medical Ltd Consultant LEARNING OBJECTIVES

1) To learn about the functional and molecular imaging research being conducted within the Radiology Department of Oxford University Hospitals NHS Trust.

ABSTRACT There is increasing functional and molecular imaging being performed in medicine. The Radiology department at the Churchill Hospital in Oxford is conducting a number of trials in these areas, and has designed these trials around interventions to measure the effect of these new techniques. It has also taken the opportunity to raise the profile of Radiology within the University, to promote greater collaboration with basic scientists, attracting increased funding, and opportunities for scientists and physicians.

RC118B Lessons Learned from the National Irish Breast Screening Program: The first 12 years–One Million Mammograms On Michelle Marie McNicholas MD (Presenter): Nothing to Disclose LEARNING OBJECTIVES 1) To review the results of the Irish National Breast Screening Program following 12 years of screening with over 1,000,000 mammograms performed. 2) To understand the essential components of setting up and maintaining a national breast screening program in Ireland. This includes the rationale for the decisions made at the outset, such as age range, frequency of screens, centralisation of service and responsibility of the screening the outset, such as age range, frequency of screens, centralisation of service and responsibility of the screening process to the end of primary surgery. 3) To understand the need for and the mechanism of developing a national registry of eligible women in the absence of a national unique identifier. 4) To understand the need for a client charter which sets out client guarantees, objectives and goals around issues of consent, timeliness of screening results and recall to assessment, biopsy results and admission for surgery and further treatment where indicated. 5) To understand the necessity of national guidelines, annual reports and external accreditation. 6) To demonstrate the essential need for ongoing review of key performance indicators (recall rate, biopsy rate, cancer detection rate, DCIS rate, open biopsy rate, false negative rate, interval cancer rate) as surrogates of program success. 7) To understand the importance of communication and feedback to clients, units, practitioners and media in maintaining uptake. 8) To understand the reporting structure and the composition of various roles within the multidisciplinary medical and surgical teams. 9) To understand the requirements for ongoing training and education of all staff - physicians, technologists, nurses, physicists, administrative staff. 10) To understand the factors affecting radiation dose to the screened population and the over-riding responsibility of the ALARA principle, such as: role of physics team, mammographic technique, equipment choice, technologist expertise and training, quality assessment. 11) To understand the operational issues of different screening units, double reading, discrepancy cases, dealing with interval cancers, dealing with outliers in key performance parameters. 12) To understand the positive spinoff s from the program including increased awareness, improving national standards in the screening and the symptomatic population and the contribution to improved diagnostic and treatment options. 13) To understand how the program achieved, maintained, and monitored performance and how it adapted to changes in practice as issues or controversies arose. 14) To discuss whether this population screening program has been a successful and cost effective health care initiative for Ireland. 15) Ultimately, to understand whether the Irish National Breast Screening Program has led to improved survival in women with breast cancer in Ireland.

RC118C MRI of Pelvic Malignancy—The View from Down Under Clair Louise Shadbolt MBChB (Presenter): Nothing to Disclose LEARNING OBJECTIVES 1) To learn about the local availability and funding of MRI in investigating pelvic malignancy that is unique to Australia. 2) To understand the current usage of Pelvic MRI in investigating pelvic malignancy in the Australian population. 3) To review some typical examples of Pelvic MRI in Oncology that illustrate the advantages of MRI in the assessment of pelvic malignancies and impact MRI has on patient management in the multidisciplinary setting.

ABSTRACT According to the Australian and New Zealand College of Radiologists' (RANZCR) website "MRI is only effective when it is likely to improve the health outcome for the patient ... although able to offer detailed images, MRI scanning is not always the most appropriate imaging". The Australian Government Department of Heath and Aging announced a press release in November 2012 of a $104.4 million Diagnostic Imaging Review Reform Package to increase access to MRI and increase cancer services: "This package means many more Australians will benefit from faster diagnosis and earlier detection of disease... From November 2012 Medicare will cover the cost of more MRI scans than ever before. Under the changes patients using MRI machines in regional Australia will have greater access..." How is MRI utilised in pelvic oncology in Australia? I will be discussing the current funding and availability of MRI in pelvic oncology in Australia. The unique geography and remoteness of some sectors of the population of Australia influences the usage of MRI. I will illustrate the important role of MRI in the management of pelvic malignancy with some classic examples.

RC118D Imaging of HCC—A Korean Perspective Byung Ihn Choi MD, PhD (Presenter): Research Consultant, Samsung Electronics Co Ltd LEARNING OBJECTIVES

1) To learn recent imaging techniques for the qualitative and quantitative diagnosis, selection of treatment methods, and evaluation of monitoring after treatment for HCC. 2) To understand the imaging findings of hepatocarcinogenesis from regenerate nodule going through low and high grade dysplastic nodule, early HCC and finally to advanced HCC. 3) To review current clinical practice guidelines including role of imaging for the diagnosis and treatment for HCC with focus on recent change of guidelines by rapid progression of imaging biomarkers.

RC120 Molecular and Functional Imaging/Surrogate Markers in Radiation Oncology

Refresher/Informatics RO MI BQ AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Sun, Nov 30 2:00 PM - 3:30 PM Location: S404CD

Participants Moderator Anca Ligia Grosu MD : Nothing to Disclose LEARNING OBJECTIVES

1) To understand challenges of morphological radiological investigations for the detection and characterization of tumor biology 1) To understand challenges of morphological radiological investigations for the detection and characterization of tumor biology and the timely assessment of tumor response in clinical cancer therapy and in clinical trials testing new therapy regimens. 2) To understand the role and the potential of functional and molecular imaging modalities and techniques used (a) prior to therapy for tumor delineation and targeting, (b) during cytotoxic therapy, such as radiation and chemotherapy for intra-treatment tumor response monitoring, and (c) after cytotoxic therapy for response assessment. 3) To apply and integrate imaging modalities into the therapeutic management of cancer. 4) To review the role of imaging as predictors of tumor control and survival and their emerging role as short-term surrogate markers for long-term therapeutic outcome of cancer treatment regimens and its potential for adaptive therapy.

Sub-Events RC120A Imaging Surrogate Markers in CNS Tumors Anca Ligia Grosu MD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Clinical problem: Limitations of the morphological/radiological investigations (CT and MRI) for the detection of the gross tumor mass and visualization of tumor biology. 2) Gross Tumor Volume (GTV) Delineation: Amino- Acids PET (AA-PET) and SPECT: a. Sensitivity and specificity of MET-PET, FET-PET and IMT-SPECT b. Comparison MET-PET, FET-PET and IMT-SPECT c. AA-PET for GTV delineation in gliomas d. Future trials. 3) Tumor Biologys: a. Glucose metabolism: FDG-PET b. Tumor proliferation: FLT-PET c. Tumor hypoxia: F-MISO-PET d. Tumor angiogenesis: RGD-PET, MRI e. Visualization of tumor stemm cells in vivo: animal-PET f. Tumor heterogeneity: MRI.

RC120B Imaging Surrogate Markers in Pelvic Tumors Nina A. Mayr MD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

RC120C Imaging Surrogate Markers in Lung Tumors Feng-Ming Kong MD, PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

MSMI21 Molecular Imaging Symposium: Oncology

Multisession Courses RO OI MI AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Mon, Dec 1 8:30 AM - 10:00 AM Location: S405AB

Participants Moderator Ronald L. Korn MD, PhD : Nothing to Disclose

Sub-Events MSMI21A Use of Novel PET Agents to Probe Tumor Biology: From Benchtop to the Clinic Jonathan Edward McConathy MD, PhD (Presenter): Speakers Bureau, Eli Lilly and Company Research Consultant, Eli Lilly and Company Research Consultant, General Electric Company Research Consultant, Blue Earth Diagnostics Ltd Research Consultant, Siemens AG LEARNING OBJECTIVES

1) Understand key molecular and metabolic targets for PET imaging in oncology. 2) Be familiar with novel PET tracers that are promising for translation into human oncologic imaging studies.

ABSTRACT

Positron emission tomography (PET) with the glucose analogue 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) has established molecular imaging as an important aspect of clinical oncology but only probes one facet of cancer metabolism. A wide range of small molecule, peptide, antibody, and nanoparticle-based PET tracers are in development for oncologic imaging and can provide important insights into tumor biology. This talk will focus on novel PET tracers that have high translational potential to diagnose, stage, and direct therapy in oncology. MSMI21B Massively Multiplexed Functional and Immunophenotypic Analysis of Solid and Liquid Tumors R. Michael Angelo MD, PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Understand the basic working principles of multiplexed ion beam imaging (MIBI). 2) Understand current research applications of MIBI. 3) Understand practical uses of MIBI in future clinical diagnostics development.

MSMI21C Clinical Metabolic MRI with Hyperpolarized Carbon-13 Agents Peder E. Larson PhD (Presenter): Research support, General Electric Company LEARNING OBJECTIVES 1) Basic principles of generating hyperpolarized carbon-13 agents for metabolic MRI. 2) Imaging methods for hyperpolarized carbon-13 agents. 3) Clinical applications.

Active Handout http://media.rsna.org/media/abstract/2014/14004190/MSMI21C sec.pdf

MSMI21D Spying on Cancer Metastasis Using Intravital Microscopy: Seeing Is Believing Laila Ritsma PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Understand the advantages of IVM and how it can be used to study dynamic processes in tumor biology and beyond. 2) Get insights into metastatic colonization. 3) Get insights into intestinal stem cell homeostasis.

ABSTRACT Purpose: Intravital microscopy can be used to visualize dynamic biological processes in their native environment. By visualizing tissues through an optical window with a two-photon microscope, cell behavior can be studied over weeks. Here, we report the development of an abdominal imaging window (AIW) for mice. We use the AIW to longitudinally follow liver metastases to link cellular behavior to successful colonization. Moreover, we use the AIW to glimpse at the short-term dynamics of intestinal stem cells (SC). Methods: A titanium AIW was implanted into the abdomen of mice. In our metastasis study we intrasplenically injected fluorescent C26 colorectal cancer cells to generate liver metastases. A splenectomy was performed to prevent outgrowth in the spleen. A daily imaging regimen was used to study liver metastases. In our SC study we used Lgr5eGFP-Ires-CreERT2/R26R-Confetti mice to visualize Lgr5+ intestinal SCs and their progeny daily. Results: We show that single extravasated tumor cells proliferate to form so called pre-micrometastases in which cells are highly migratory. Once the clones condense into micrometastases, cell migration is diminished. Surprisingly, during the pre-micrometastasis stage migration is positively correlated with proliferation. Blocking of migration during this stage greatly reduced metastatic load, suggesting that cell migration during the pre-micrometastasis stage is a contributing step to colorectal liver metastasis. During intestinal homeostasis, we show that SCs in the upper part of the niche can be passively displaced out of the niche after division of a near-by SC. Moreover, we found that SCs in the central part of the niche experience a survival advantage over cells in the border. SCs were able to transfer between border and center region in both directions, endowing each SC with long-term self-renewal potential. Conclusion: We conclude that IVM is an important imaging platform to study complex dynamic processes in vivo.

MSMI22 Molecular Imaging Symposium: Radiogenomics: Linking Imaging to the Future - How to Prepare for the Radiogenomic Revolution

Multisession Courses RS MI BQ AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Mon, Dec 1 10:30 AM - 12:00 PM Location: S405AB

Participants Moderator Ronald L. Korn MD, PhD : Nothing to Disclose LEARNING OBJECTIVES

1) To understand how radiogenomics enables translation of everyday CT, MRI and PET findings into clinical molecular markers. 2) To understand emerging clinical applications of radiogenomics. 3) To discuss and highlight new directions and challenges for the field of radiogenomics.

Sub-Events MSMI22A Integrating Histology and Genomics: Spatial and Molecular Heterogeneity of Immune Infiltration in Triple-negative Breast Tumours Yinyin Yuan PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

MSMI22B An Introduction to the Technical Framework for Quantitative Biomarker Imaging Analysis for Radiogenomic Analysis Jong Hyo Kim PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

MSMI22C Radiogenomics-multiscale Molecular Imagaing: Applications in Clinical Practice Michael D. Kuo MD (Presenter): Consultant, Boehringer Ingelheim GmbH Consultant, Confluence Life Sciences, Inc LEARNING OBJECTIVES

View learning objectives under main course title.

MIS-MOA Molecular Imaging Monday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Mon, Dec 1 12:15 PM - 12:45 PM Location: S503AB

Participants Moderator Heike E. Daldrup-Link MD : Nothing to Disclose Moderator Matthias Johannes Eiber MD : Speaker, Siemens AG Speaker, Astellas Group Speaker, Johnson & Johnson

Sub-Events MIS123 Sentinel Lymph Node Localisation in Melanoma Using a Novel Magnetic Tracer for Magnetic Resonance Imaging (Station #7) Bauke Anninga (Presenter): Nothing to Disclose , Samantha White : Nothing to Disclose , Paul Malcolm MRCP, FRCR : Speaker, General Electric Company , Joost Klaase : Nothing to Disclose , Bennie ten Haken PhD : Nothing to Disclose , Suzan Vreemann : Nothing to Disclose , Roland Bezooijen MD : Nothing to Disclose , Marc Moncrieff : Nothing to Disclose , Margaret Anne Hall-Craggs MD : Nothing to Disclose , Michael Douek MD : Nothing to Disclose PURPOSE

Sentinel lymph node biopsy (SLNB) in melanoma is currently performed using radioisotope and blue dye injections. We recently developed a novel magnetic technique for SLNB using a superparamagnetic iron-oxide (SPIO) tracer and a hand-held magnetometer for sentinel lymph node (SLN) localisation. The aim of this study was to assess the ability of magnetic resonance imaging (MRI) to identify lymphatic tracts and the SLN pre-operatively in patients with extremity melanoma, following administration of an SPIO tracer.

METHOD AND MATERIALS

Patients with primary cutaneous melanoma scheduled for SLNB, and clinically AJCC stages IB-IIC, were recruited into the MRI sub-protocol of the MELAMAG Trial. SLN localisation was performed after administration of radioisotope (99mTc) and SPIO tracer (Sienna+, Endomagnetics Ltd.) with lymphoscintigraphy and MRI, respectively. For MRI localisation, pre-injection T1-weighted and T2-weighted (T2W) turbo-spin echo scans were followed by an intradermal injection of magnetic tracer and local massage at the injection site. T2W scans were repeated 15 minutes post-injection. Intra-operatively the magnetometer (SentiMag, Endomagnetics Ltd.) was used to localise the SLN(s), followed by the gamma probe and blue dye. Pre-operative lymphoscintigraphy was compared to pre-operative MRI by two independent radiologists.

RESULTS Five patients with extremity melanoma (4 lower, 1 upper) were recruited. In all cases MRI+SPIO tracer identified the same number and sites of lymphatic drainage compared to lymphoscintigraphy. In 4 cases MRI and lymphoscintigraphy showed identical numbers of lymphatic channels. In 3 cases the total number of SLNs identified was the same for both imaging modalities.

CONCLUSION

SLN localisation with MRI in melanoma using a novel magnetic tracer is feasible. Pre-operative localisation correlates well with intra-operative findings. Additional evaluation is needed in larger and more challenging (including head, neck and truncal primary melanoma) cohorts of patients.

CLINICAL RELEVANCE/APPLICATION

This novel approach of MRI with an SPIO tracer can provide high resolution, pre-operative SLN localisation without the use of radiation.

MIS124 A Pocket Phantom and Method for Per-patient Quantitative Calibration of PET/CT Scans [ MI Scavenger Hunt! ] (Station #8) Paul Eugene Kinahan PhD (Presenter): Research Grant, General Electric Company Co-founder, PET/X LLC , Darrin W Byrd MS : Nothing to Disclose , Brian Helba : Employee, Kitware, Inc , Xiaoxiao Liu PhD : Employee, Kitware, Inc , Joshua Levy : Stockholder, The Phantom Laboratory President, The Phantom Laboratory Stockholder, Image Owl, Inc , Keith Allberg : Employee, RadQual, LLC , Ricardo Avila MS : Employee, Kitware, Inc Shareholder, Kitware, Inc Consultant, F. Hoffmann-La Roche Ltd PURPOSE In clinical trials and clinical practice, standardized uptake values (SUVs) from PET images can be used to assess response to therapy. However, PET images are subject to bias from scanner calibration and resolution effects. PET calibration phantoms can be used, however, resolution loss causes bias for objects smaller than 3-4 cm, limiting feasibility. We present a method that compensates for these quantitative errors on a per-patient and per-scan basis.

METHOD AND MATERIALS We constructed a small rectangular PET/CT 'pocket' phantom containing a linear array of three long-lived 68Ge/68Ga sources, each 1.5 cm in diameter with a NIST traceable activity concentration. This was coupled with an image-based estimation process that retrospectively decoupled bias effects from scanner calibration and resolution effects. The pocket phantom was imaged alongside a series of phantoms representing different levels of complexity of PET imaging. Different levels of calibration bias and image smoothing were introduced. Using the reconstructed image and known sphere geometries and locations, an ideal image was created that had no blurring and no bias. The analysis software then estimated the bias and applied a blurring kernel G(σx, σy, σz) to create a model image. By iteratively minimizing the differences between the PET image and the model image, the algorithm estimated the resolution, defined as the full width at half maximum of G, and the overall bias in the PET image for each combination of measurement partners for the three spheres.

RESULTS In the reconstructed PET images with artificially introduced different levels of bias and image smoothing, the combination of the pocket phantom and the estimation algorithm successfully decoupled the effects of bias and resolution to within 6% residual bias.

CONCLUSION It is possible to simultaneously estimate the global bias and resolution of reconstructed images with a small long-lived phantom with sources smaller than the PET resolution limit of roughly 3 cm.

CLINICAL RELEVANCE/APPLICATION The use of a small phantom, when coupled with appropriate estimation algorithms, can provide a per-patient and per-scan method for absolute calibration of PET image data. Per scan phantom use and calibration has the potential to improve the effectiveness of clinical trials and clinical practice.

MIS125 Characterization of Glycolytic Activity and Perfusion in a Renal Cell Carcinoma Mouse Model during Sunitinib Response and Resistance with Hyperpolarized 13-C-pyruvate MRI (Station #9) Leo Lee Tsai MD, PhD (Presenter): Co-founder, Agile Devices Inc Stockholder, Agile Devices Inc Research Consultant, Agile Devices Inc , Xiaoen Wang MD : Nothing to Disclose , Gopal Varma PhD : Nothing to Disclose , Rupal Bhatt : Nothing to Disclose , David C. Alsop PhD : Research support, General Electric Company Royalties, General Electric Company , Aaron Keith Grant PhD : Nothing to Disclose PURPOSE

Renal cell carcinomas (RCC) demonstrate high rates of glycolysis, associated with high expression of the glucose transporter GLUT1, which is in turn regulated by hypoxia-induced factors (HIF). Here we use hyperpolarized 13-C pyruvate (h13C-pyruvate) to provide in vivo monitoring of glycolysis and perfusion in a renal cell carcinoma (RCC) xenograft mouse model treated with sunitinib, and to correlate with GLUT1 and CD34 expression.

METHOD AND MATERIALS Four mice were implanted with A498 VHL-deficient RCC. Two were treated with sunitinib, and two controls were administered phosphate-buffered saline (PBS). One sunitinib-treated mice was imaged 7 days after treatment initiation, the other 32-days post-treatment, at resistance. Control mice were imaged pre-PBS and 6-7 days following PBS. Tumors were harvested after final images for immunohistological analysis. MRI was performed at 9.4 T using: (1) Proton-T2-weighed rapid acquisition with refocused echoes (RARE) sequence for anatomical localization, (2) h13C-pyruvate imaging with echo-planar spectroscopic imaging (EPSI), and (3) arterial-spin-label (ASL) perfusion mapping with flow-sensitive inversion-recovery.

RESULTS

Control tumors treated with PBS show high uptake of C13-pyruvate and conversion into lactate (Figure 1a- proton image, 1b- lactate image overlay). Sunitnib-treated tumor at 7d demonstrated decreased perfusion on ASL corresponding to decreased C13-pyruvate uptake, and altered lactate levels at both response and resistance. High GLUT1 expression was sustained during growth, treatment, and at resistance, while CD-34 expression was reduced during sunitinib response, and restored at resistance, as demonstrated in Figures 2a-2c (GLUT1-red, CD34-green, Hoechst nuclei staining-blue).

CONCLUSION

Glycolytic metabolism is altered during RCC response to sunitinib and subsequent resistance, though overall activity is sustained, as demonstrated by persistent GLUT1 expression. C13-pyruvate uptake correlates with perfusion as measured by ASL and CD34 expression.

CLINICAL RELEVANCE/APPLICATION

h13C-pyruvate MRI provides vivo assessment of glycolytic activity and perfusion within an RCC model, correlating to treatment response and resistance. This method has translational potential for clinical tumor monitoring in patients.

MIE107 Imaging of Drugs in the Brain Following Intranasal Delivery (Station #10) Michael C. Veronesi MD, PhD (Presenter): Nothing to Disclose , Shih-Hsun Cheng PhD : Nothing to Disclose , Hsiu-Ming Tsai PhD : Nothing to Disclose , Hannah J. Zhang PhD : Nothing to Disclose , Marta A. Zamora BS : Nothing to Disclose , James Vosicky : Nothing to Disclose , Devkumar Mustafi PhD : Nothing to Disclose , Xiaobing Fan PhD : Nothing to Disclose , Leuwei Lo PhD : Nothing to Disclose , Chin-Tu Chen PhD : Stockholder, EVO Worldwide Stockholder, Medical Simulation Corporation Stockholder, EDDA Technology, Inc Stockholder, EnDepth Vision Systems, LLC Research Consultant, DxRay, Inc Advisor, RefleXion Medical Inc , Michael Walter Vannier MD : Nothing to Disclose TEACHING POINTS Intranasal (IN) drug administration provides a promising alternative to systemic administration since a direct anatomic pathway exists between the olfactory neuroepithelium of the nasal cavity and the brain. Several drugs have already been approved for IN application (e.g., oxytocin in autism), and others may be approved in the near future. Since little is known about the spatial and temporal characteristics of IN drug delivery, a method of localizing their presence in the brain of a living animal is needed. 1. Nanotheranostics, the combination of diagnostic and therapeutic function in a single system through nanotechnology, has the potential to improve drug administration in the central nervous system. 2. MRI and CT-PET are becoming key tools in nanotheranostics since they can help determine the fate of nanoparticles containing drugs in the brain. 3. A major advantage of in vivo imaging in experimental IN delivery is its noninvasive nature and potential repeatability without the need for sacrificing animals. Thus, this imaging technology can be more easily translatated to humans.

TABLE OF CONTENTS/OUTLINE 1. Nanotheranostics. 3. What's in a nanoparticle? 4. The nose to brain route. 4. CT-PET, MRI and their application to small animal drug delivery. 5. From benchtop to the bedside. 6. The future of nanotheranostics.

MIE004-b Clinical Relevance of Emerging Molecular Imaging Modalities in Prostate Cancer (custom application computer demonstration) Nii O. Koney MD, MBA : Nothing to Disclose , Yi Chen Zhang MD (Presenter): Nothing to Disclose , Elina Zaretsky MD, MA : Nothing to Disclose , Munir Ghesani MD : Nothing to Disclose , E. Gordon Depuey MD : Consultant, BioClinica, Inc Consultant, ICON plc Steering Committee, Adenosine Therapeutics, LLC , Alexander Cates Kagen MD : Speakers Bureau, Bayer AG TEACHING POINTS There is controversy over the utility of PSA as a screening tool because of its inability to differentiate indolent from aggressive cancer types. Molecular imaging is well positioned to address this challenge. Although the current workhorse for molecular imaging, 18F-FDG, is not effective in prostate cancer, several new agents have been/are being developed. For example, 11C- or 18F-labeled choline are emerging tracers for detecting local and metastatic prostate cancer. We will review the latest advances in the use of molecular imaging to screen and diagnose prostate cancer. We will evaluate the perceived clinical relevance of current and emerging tracers using preliminary results from a survey of practicing referring clinicians at our institution that show awareness of molecular imaging and need to demonstrate superiority over conventional imaging as a guide

TABLE OF CONTENTS/OUTLINE Introduction and Background on Molecular Imaging in Prostate Cancer Review of current and emerging prostate cancer imaging tracers Review of imaging protocol: patient selection, patient preparation, radiopharmaceutical preparation Evaluation of clinical relevance utilizing preliminary results from a survey of practicing referring clinicians

MIS-MOB Molecular Imaging Monday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Mon, Dec 1 12:45 PM - 1:15 PM Location: S503AB

Sub-Events MIS126 Utility of Gadoxetate Disodium (Eovist)-enhanced MRI in Prostate Cancer Imaging (Station #7) Linda Johnson : Nothing to Disclose , Harsh Agarwal : Employee, Koninklijke Philips NV , Kinzya Bernice Grant MD : Nothing to Disclose , Marcelino Bernardo BS : Nothing to Disclose , Sandeep Sankineni MD (Presenter): Nothing to Disclose , Cindy Chau : Nothing to Disclose , William Dahut : Nothing to Disclose , Maria Merino MD : Nothing to Disclose , Bradford J. Wood MD : Researcher, Koninklijke Philips NV Researcher, Celsion Corporation Researcher, BTG International Ltd Researcher, , W. L. Gore & Associates, Inc Researcher, Delcath Systems, Inc Pending research funded, Perfint Healthcare Pvt Ltd Patent agreement, VitalDyne, Inc Intellectual property, Koninklijke Philips NV Intellectual property, BTG International Ltd , Peter Pinto : Nothing to Disclose , William Douglas Figg Pharm D, MBA : Nothing to Disclose , Peter L. Choyke MD : Researcher, Koninklijke Philips NV Researcher, General Electric Company Researcher, Siemens AG Researcher, iCAD, Inc Researcher, Aspyrian Therapeutics, Inc Researcher, ImaginAb, Inc Researcher, Aura , Baris Turkbey MD : Nothing to Disclose PURPOSE

The organic anion transporter polypeptide 1B3 (OATP1B3) is a testosterone transporter that is expressed de novo in prostate cancer and represents a possible mechanism of tumor growth. It represents an important prognostic indicator since OATP1B3 expression correlates with Gleason score and is associated with a decreased overall survival rate. Gadoxetate disodium (Eovist) is a MRI contrast agent that is a substrate for OATP1B3, allowing visualization of OATP1B3+ tumors on MRI. The purpose of this study is to determine if gadoxetate disodium-enhanced MRI can be utilized as a biomarker in patients with localized and metastatic disease.

METHOD AND MATERIALS Preliminary results include 8 patients with localized prostate cancer and 1 patient with metastatic CRPC (accrual is still continuing), with a mean age of 66 years and mean PSA of 12.68 ng/ml, all of whom had gadoxetate disodium-enhanced multi-parametric MRI scans obtained at 3 Tesla using a 32-channel cardiac coil. Gadoxetate disodium was administered intravenously and T1 TSE imaging was obtained at 10, 20, 40, and 60 minutes post injection. Post injection T1 TSE images were compared with pre-contrast images for each patient. Relative enhancement ratios were calculated over the tumor region for each patient at the 4 post-injection time points. Two-tailed Student's t-test was used to compare signal enhancement between localized and metastatic cancer patients. Verification of OATP1B3 expression by immunohistochemistry will be performed in single batch once accrual of this trial is completed.

RESULTS

Mean enhancement ratios are shown in Table 1. There was a statistically significant difference between the enhancement ratios between localized and metastatic prostate cancer patients at 10 and 20 minutes post-injection gadoxetate disodium-enhanced MRI.

CONCLUSION

There is a significant difference between gadoxetate disodium enhancement in localized disease and metastatic CRPC. Gadoxetate disodium-enhanced MRI can help in determining OATP1B3 expression status of prostate cancer lesions.

CLINICAL RELEVANCE/APPLICATION

Gadoxetate disodium-enhanced MRI may provide additional prognostic information, which can assist in risk stratification of patients with localized and metastatic prostate cancer.

MIS127 Visualizing Immune Processes with 3D Magnetic Particle / Magnetic Resonance Fusion Imaging: Proof of Concept in a Murine Graft-versus-Host Disease Model (Station #8) Stefan Marco Herz MD (Presenter): Nothing to Disclose , Patrick Vogel : Nothing to Disclose , Martin A. Ruckert : Nothing to Disclose , Christian Brede : Nothing to Disclose , Thomas Kampf : Nothing to Disclose , Simon Veldhoen MD : Nothing to Disclose , Peter Michael Jakob PhD : Nothing to Disclose , Andreas Beilhack : Nothing to Disclose , Volker C. Behr : Nothing to Disclose , Thorsten Alexander Bley MD : Nothing to Disclose PURPOSE Here we investigated the feasibility of fusing 3D magnetic particle imaging (MPI) and magnetic resonance imaging (MRI) to visualize dynamic immune cell processes in a murine graft-versus-host disease (GVHD) model. MPI, a novel imaging tool, was used to detect monoclonal antibodies conjugated to superparamagnetic iron oxide particles to track T cell populations.

METHOD AND MATERIALS

Acute GVHD was induced in myeloablativly (9 Gy) conditioned BALB/c mice (H-2d, CD90.2) by transplanting allogeneic luciferase (luc+) CD90.1+ T cells from transgenic C57BL/6.L2G85 mice together with T cell depleted bone marrow cells from C57BL/6 wild type mice. Controls only received T cell depleted bone marrow. 3 days after transplantation in vivo bioluminescence imaging (BLI) was performed before i.v. administration of a donor T cell specific CD90.1 monoclonal antibody conjugated to superparamagnetic iron oxide nanoparticles. 3h and 6h later MPI and MRI was performed using the same holder to ensure identical positioning of mice for both modalities. 3D MPI was conducted with a homemade traveling wave MPI scanner (gradient: 4T/m, bore: 29 mm). MRI was performed with a 7T scanner with a 60 mm horizontal bore. A 3D T2-weighted rapid acquisition with refocused echoes (RARE) sequence was used to provide anatomical background. MPI and MRI data were reconstructed and fused manually.

RESULTS

MPI proofed sensitive to visualize donor T cells after hematopoietic cell transplantation. In vivo BLI as reference standard revealed high signals in the cervical, mesenteric and splenic region indicating the presence of alloreactive T cells in mice within secondary lymphoid organs during GVHD initiation. In MPI/MRI fusion images high MPI-signal in the spleen was observed. In contrast, bone marrow controls displayed only baseline signals.

CONCLUSION

These initial results demonstrate that 3D MPI/MRI fusion imaging with labeled antibodies is a feasible tool to assess dynamic immune cell processes such as acute GVHD. Further technical improvements are necessary to transfer this technique from preclinical animal models to human imaging.

CLINICAL RELEVANCE/APPLICATION

3D fusion of magnetic particle imaging and whole-body MRI is a promising biotechnical approach with the potential to provide radiation-free molecular imaging in humans.

MIS128 Real-time Ultrasound Elastography for Assessment of Response to Brentuximab Vedotin Treatment in Relapsed and Refractory Hodgkin Lymphoma (Station #9) Ettore Squillaci MD (Presenter): Nothing to Disclose , Francesca Bolacchi : Nothing to Disclose , Marco Antonicoli : Nothing to Disclose , Simone Altobelli : Nothing to Disclose , mariangela massaccesi MD : Nothing to Disclose , Giovanni Simonetti MD : Nothing to Disclose PURPOSE

Brentuximab vedotinis is a possible treatment option in patients suffering from relapsed and refractory Hodgkin lymphoma (HL). This study evaluates the feasibility of realtime ultrasound elastography (RTE) for monitoring treatment response to brentuximab vedotin in patients with relapsed and refractory HL.

METHOD AND MATERIALS Fifteen consecutive, heavily pretreated patients with relapsed and refractory HL treated with brentuximab vedotin were included in the study. RTE was performed during treatment after a median of 3 cycles (range, 2-5 cycles). Elastographic patterns were given scores of 1-5 according to the percentage of high elasticity (hard) areas in the lymph node. Elastographic patterns 1, 2, 3, 4, and 5 were assigned elastography scores (ES) of 1, 2, 3, 4, and 5, respectively.

RESULTS

The median progression-free survival (PFS) was 14.2 months and PFS at 12 months was 63%. Patients treated with brentuximab vedotin and elastography score of 2 and 3 demonstrated a significantly prolonged PFS compared to patients with elastografic score of 4 and 5. The 1-year PFS was 76% in patients with an elastography score of 2 and 3, whereas patients with an elastography score of 4 and 5 had a worse outcome with a 1-year PFS of 24% (p = 0.015)

CONCLUSION

Real time Elastography can provide non-invasive, real-time tool for assessment of response to brentuximab vedotin treatment in relapsed and refractory Hodgkin lymphoma.

CLINICAL RELEVANCE/APPLICATION

Real time elastography could be a reliable tool for the assessment of refractory Hodgkin lymphoma response to brentuximab vedotin treatment. MIE113 Stem Cell Tracking with Clinically Applicable MR Contrast Agents (Station #10) Hossein Nejadnik MD, PhD (Presenter): Nothing to Disclose , Fanny Chapelin MS : Nothing to Disclose , olga lenkov BSC : Nothing to Disclose , Heike E. Daldrup-Link MD : Nothing to Disclose TEACHING POINTS Stem cell-therapies and other cell therapies have become a powerful new tool for tissue regeneration. The field is expanding and rapidly entering clinical applications, with currently over 4000 ongoing clinical stem cell trials worldwide. Imaging technologies need to diagnose stem cell delivery and engraftment at the target site and provide information about viability, differentiation and tumorigenic potential of the cells. Our group and others established immediately clinically applicable stem cell labeling and tracking methods with magnetic resonance (MR) contrast agents, which combine approaches for radiation free cell tracking with the high soft tissue contrast and high spatial resolution of MRI. This exhibition will demonstrate basic cell handling technologies for radiologists, explain various labeling methods, discuss safety considerations, and show examples of stem cell tracking with commercially available, FDA approved iron nanoparticles and gadolinium chelates

TABLE OF CONTENTS/OUTLINE 1) Explain cell culture techniques, relevant for Radiologists 2) Review previous and currently available MR contrast agents for cell labeling 3) Elaborate labeling methods 4) Discuss safety considerations for stem cell labeling 5) Provide examples of studies using labeled stem cells in vitro and in vivo 6) Explain prospective clinical applications

MSMI23 Molecular Imaging Symposium: Cellular and Microenvironment Imaging

Multisession Courses MI BQ AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Mon, Dec 1 1:30 PM - 3:00 PM Location: S405AB

Participants Moderator Michael D. Kuo MD : Consultant, Boehringer Ingelheim GmbH Consultant, Confluence Life Sciences, Inc LEARNING OBJECTIVES

1) To explore new and emerging technologies for cellular and microenvironment imaging. 2) To learn and appreciate how new cellular and microenvironment imaging technologies are being applied to address both clinical and research questions.

Sub-Events MSMI23A Imaging Serum Biomarkers Jason S Lewis PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) The audience will learn that despite their considerable advantages, many circulating biomarkers have well documented limitations. 2) The audience will learn about imaging tool that can be used to deconvolute the meaning of inconclusive circulating biomarker levels.

ABSTRACT For good reason, discovering biomarkers that can be assayed from biological fluids has long been regarded as a "holy grail" for medical diagnostics. Indeed, several decades of systematic research have identified many secreted molecules differentially regulated in the context of malignant cancers that are now routinely measured in man to screen for disease onset, develop prognoses, and monitor tumor response or recurrence. Their rapid commercialization, favorable economics, and simple experimental outputs (lending itself to standardization for multi-center trials) have engendered the widespread use of many analytical platforms to measure serum biomarker levels (e.g. ELISAs). The resulting vast body of epidemiological data has consistently reinforced the notion that, while exciting progress has been made, we have yet to find a single, "smoking-gun" serum biomarker that can be effectively applied to address all of the above-mentioned clinical issues for a given cancer. However, despite their considerable advantages, many circulating biomarkers have well documented limitations. One prominent shortcoming in oncology is a high frequency of false positive indications for malignant disease in upfront diagnosis. Because one common cause of false positivism is biomarker production from benign disorders in unrelated host tissues, we hypothesized that probing the site(s) of biomarker secretion with an imaging tool could be a broadly useful strategy to deconvolute the meaning of foreboding but inconclusive circulating biomarker levels. In preparation to address this hypothesis clinically, we have developed a series of imaging agents that specially target serum biomarkers, and as a result overcome the documented limitations of these tests.

MSMI23B Seeing the Forest and the Trees: Visualizing Intact Lung Alveoli at Cellular Resolution Tushar Desai MD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Describe the fundamental three dimensional structure of the pulmonary alveolus and the intimate physical association between the gas exchange surface and underlying capillary mesh. 2) Learn the basic cellular composition of the pulmonary alveolus and how the cell types are spatially distributed. 3) Understand how the morphologies and positions of alveolar cell types relate to their specific function and optimize the capacity for tidal breathing and efficient gas exchange.

MSMI23C CLARITY for Imaging Structurally Intact Systems Kwanghun Chung PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

MSMI23D Nanodiamond Platforms Enhance Imaging and Drug Delivery Efficacy Dean Ho PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

MSMI24 Molecular Imaging Symposium: Molecular Brain Imaging: From Research to Clinical Applications

Multisession Courses MI BQ NR MI BQ NR AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Mon, Dec 1 3:30 PM - 5:00 PM Location: S405AB

Participants Moderator Satoshi Minoshima MD, PhD : License agreement, General Electric Company Research Grant, Koninklijke Philips Electronics NV Research Grant, Hitachi, Ltd Research Consultant, Hamamatsu Photonics KK Grant, Nihon Medi-Physics Co, Ltd Research Grant, Astellas Group Research Grant, Seattle Genetics, Inc LEARNING OBJECTIVES

1) To discuss new molecular brain imaging techniques that are available in the clinic. 2) To explain how basic research has been translated to clinical applications. 3) To discuss approval processes that are necessary to establish clinical molecular brain imaging.

Sub-Events MSMI24A Amyloid Imaging: Translational Research to Clinical Applications Alexander Drzezga MD (Presenter): Consultant, Siemens AG Consultant, Eli Lilly and Company Consultant, General Electric Company Consultant, Piramal Enterprises Limited Speaker, Siemens AG Speaker, Eli Lilly and Company Speaker, General Electric Company Speaker, Piramal Enterprises Limited LEARNING OBJECTIVES

View learning objectives under main course title.

MSMI24B How Molecular Imaging Contributes to Movement Disorders? Current and Future Kirk A. Frey MD, PhD (Presenter): Consultant, MIM Software Inc Consultant, General Electric Company Consultant, Eli Lilly and Company Consultant, Piramal Enterprises Limited Consultant, Siemens AG Research funded, General Electric Company Stockholder, General Electric Company Stockholder, Novo Nordisk AG Stockholder, Bristol-Myers Squibb Company Stockholder, Merck & Co, Inc Stockholder, Medtronic, Inc LEARNING OBJECTIVES

View learning objectives under main course title. MSMI24C Quantitative Analysis and Interpretation of Molecular Brain Imaging Satoshi Minoshima MD, PhD (Presenter): License agreement, General Electric Company Research Grant, Koninklijke Philips Electronics NV Research Grant, Hitachi, Ltd Research Consultant, Hamamatsu Photonics KK Grant, Nihon Medi-Physics Co, Ltd Research Grant, Astellas Group Research Grant, Seattle Genetics, Inc LEARNING OBJECTIVES View learning objectives under main course title.

MSMI24D Making Molecular Brain Imaging Available in the Clinic: FDA and CMS Peter Herscovitch MD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

View learning objectives under main course title.

MSAS32 Imaging Updates–New Technology Practices (Sponsored by the Associated Sciences Consortium) (An Interactive Session)

Multisession Courses

NM MR MI AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Tue, Dec 2 10:30 AM - 12:00 PM Location: S105AB

Participants Moderator Steven P DeColle : Nothing to Disclose Moderator Cindy R. Comeau BS, RT : Nothing to Disclose

Sub-Events MSAS32A Trends in Hybrid Imaging PET/MR David Walter Jordan PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES 1) Describe the main features, advantages of simultaneous PET-MRI scanners. 2) Describe the main features, advantages of sequential PET-MRI scanners. 3) Describe current clinical uses of PET-MRI. 4) Describe future PET-MRI applications that are currently under investigation.

MSAS32B MRI Safety–Facing the Challenges-PET/MR Karen E Smith MSc (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Identify the safety challenges of PET/MRI from both a technologist and patient perspective. 2) Describe the technical challenges of PET/MRI compared to PET/CT. 3) Recognize various potential workflow considerations and challenges in PET/MRI. 4) Analyze the difficulties with the implementation of PET/MRI and ways to overcome these.

MSAS32C Everyone on Board: Creating an Opportunity for Flat Collaboration and Safe Collegiate Working in Molecular Imaging Marc Griffiths MSc (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Determine the key health and safety issues for a Nuclear Medicine Technologist working in a PET/MRI unit. 2) Explore how a multi-professional approach to delivering patient care may arise from working within a hybrid imaging environment. 3) What are the opportunities and challenges associated with introducing new automated software platforms within a hybrid imaging environment. 4) What could you learn, in terms of counselling skills, from your nursing colleagues, which may benefit oncology patients within a hybrid imaging environment.

SSG08 Molecular Imaging (Inflammation/Arthritis)

Scientific Papers MI AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Tue, Dec 2 10:30 AM - 12:00 PM Location: S504CD

Participants Moderator Heike E. Daldrup-Link MD : Nothing to Disclose Moderator Michael Stanley Gee MD, PhD : Nothing to Disclose

Sub-Events

SSG08-01 Molecular Imaging of Inflammation in Inflammatory Bowel Disease with Ultrasound: Reproducibility and Dose Escalation Study in Swine Huaijun Wang MD, PhD (Presenter): Nothing to Disclose , Stephen A. Felt DVM, MPH : Nothing to Disclose , Ismayil Guracar : Employee, Siemens AG , Steven B. Machtaler PhD : Nothing to Disclose , Thierry Bettinger : Employee, Bracco Group , Juergen Karl Willmann MD : Research Consultant, Bracco Group Research Grant, Siemens AG Research Grant, Bracco Group PURPOSE

To assess reproducibility and optimal dosing for ultrasound molecular imaging (USMI) of inflammation using a clinically translatable dual P- and E-selectin-targeted contrast agent (MBSelectin) in a porcine model of acute terminal ileitis.

METHOD AND MATERIALS An acute terminal ileitis model was established in 17 pigs (ileitis pig). Another 3 pigs without inflammation served as controls. USMI was performed with a clinical system (Acuson Sequoia 512, Siemens; transducer 15L8W). Increasing doses of MBSelectin (0.5, 1, 2.5, 5, 10, and 20×108MB/kg) were injected and a total of 18 different segments of ileitis were imaged in an intra-animal comparison study. To test the reproducibility of USMI, scans of the same anatomical locations were repeated twice following both MBSelectin and non-targeted control microbubble (MBControl) administrations. After imaging, scanned ileal segments were analyzed ex vivo for both inflammation grade on HandE staining and for expression of selectins on immunofluorescence staining.

RESULTS

Signal intensities increased with higher doses of MBSelectin. However, further increase of the contrast agent dose beyond 5×108MB/kg resulted in a relatively lower further signal increase compared to lower doses (P=0.01), suggesting that the signal reached a plateau at a dose of approximately 5×108MB/kg. Using a dose of 5×108MB/kg, USMI was highly reproducible with an intraclass coefficient of 0.88 (95%CI, 0.25-0.99) using MBSelectin and of 0.84 (95%CI, 0.24-0.98) using MBControl. Administration of MBSelectin in ileitis resulted in a significantly higher (P<0.001) imaging signal compared to control ileum. Also, imaging signal using MBSelectin was significantly higher (P<0.001) compared to MBControl in ileitis. In control ileum, imaging signal was not significantly different (P=0.06) with MBSelectin or MBControl. Ex vivo analysis showed significantly higher inflammation scores and expression of selectins in acute ileitis compared to control ileum (P<0.05, Fig 1).

CONCLUSION Quantitative measurements of inflammation obtained by selectin-targeted USMI are highly reproducible in a porcine ileitis model and correlate well with the extent of inflammation on histology.

CLINICAL RELEVANCE/APPLICATION

USMI of inflammation is reproducible and quantitative and can be further developed for monitoring patients with inflammatory bowel disease.

SSG08-02 Magnetic Resonance gagCEST Imaging of the Human Lumbar Intervertebral Disc: Age Dependency of Glycosaminoglycan Content Christoph Schleich (Presenter): Nothing to Disclose , Anja Lutz : Nothing to Disclose , Benjamin Schmitt : Nothing to Disclose , Hans-Joerg Wittsack PhD : Nothing to Disclose , Gerald Antoch MD : Speaker, Siemens Medical AG Speaker, Bayer AG Speaker, BTG International Ltd , Falk Roland Miese MD : Nothing to Disclose PURPOSE

The objective of this study was to investigate the age dependency of glycosaminoglycan (GAG) content in the human intervertebral disc (IVD) using biochemical MRI with glycosaminoglycan chemical exchange saturation transfer (gagCEST).

METHOD AND MATERIALS 25 healthy volunteers (mean age 46, range: 24 - 69 years, 17 females, and 8 males) were examined with a prototype gagCEST imaging sequence at a 3T MR scanner (Magnetom Trio; Siemens Healthcare). The CEST prototype gagCEST imaging sequence at a 3T MR scanner (Magnetom Trio; Siemens Healthcare). The CEST presaturation module consisted of a series of 6 Gaussian-shaped RF pulses with B1 amplitude of 1.5 µT averaged over time (B1-CWAE). The duration of each saturation pulse and interpulse delay was 100 msec. In order to increase SNR, 6 signal averages were used. After motion correction with the prototype software fMRLung (Siemens Healthcare), CEST evaluation was performed in the lumbar IVDs L2/3 - L5/S1 using the magnetization transfer asymmetry (MTRasym = MSat/M0(-Δω) - MSat/M0(Δω)) value as a method to assess gagCEST effects (figure 1). Region of interest based analysis was performed for the nucleus pulposus (NP) and the annulus fibrosus (AF). The volunteers were categorized in five age classes: 20-29 years, 30-39 years, 40-49 years, 50-59 years and 60-69 years (figure 1). Each group consisted of five volunteers. Only IVDs with Pfirrmann grade 2 were included.

RESULTS

We found significantly lower gagCEST values in NP and AF with increasing age. NP showed higher gagCEST values compared to AF (figure 1). There was a significant correlation between age and GAG content of nucleus pulposus (r = -0.592; p = 0.01). There was a significant correlation between age and gag content of annulus fibrosus (r = -0.582; p = 0.01; figure 2).

CONCLUSION

Our study suggests age dependency of intervertebral disc composition. gagCEST imaging is sensitive to age dependent cartilage visualization, despite morphologically healthy intervertebral discs (Pfirrmann grade 2).

CLINICAL RELEVANCE/APPLICATION

Biochemical imaging with gagCEST of cartilage composition is feasible in IVDs. Our study suggests age dependency of intervertebral disc composition. Lumbar IVD degeneration is a condition with high incidence and clinical as well as economical relevance. gagCEST at 3T is a new and promising tool for the research of this disease.

SSG08-03 Diagnosis of Stem Cell Apoptosis in Arthritic Joints with MRI Hossein Nejadnik MD, PhD (Presenter): Nothing to Disclose , Deju Ye PhD : Nothing to Disclose , olga lenkov BSC : Nothing to Disclose , Jessica Donig BA : Nothing to Disclose , Jianghong Rao PhD : Nothing to Disclose , Heike E. Daldrup-Link MD : Nothing to Disclose PURPOSE Limited survival of transplanted stem cells represents a significant bottleneck for successful cartilage regeneration outcomes. The goal of this study was to develop a non-invasive MR imaging test for detection of stem cell apoptosis, using a caspase-3-activatable small molecular Gd-chelate (C-SNAM).

METHOD AND MATERIALS The C-SNAM probe underwent extensive nanocharacterization by relaxivity measurements, high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Viable and apoptotic (Mitomycin C treated) rat adipose derived stem cells (rASCs) were incubated with C-SNAM or a non-activatable control Gd-chelate and underwent in vitro MR imaging. Then, five athymic rats, with implanted viable or apoptotic Fluc-transduced rASCs in osteochondral defects, underwent MR and optical imaging before and after intra-articular injection of C-SNAM. T1-relaxation times of different groups were compared with a Student's t-test, using a p < 0.05.

RESULTS The r1 relaxivity of the C-SNAM probe increased from 10.2 ± 1.5 mM-1s-1 to 19.0 ± 0.5 mM-1s-1, after activation by caspase-3 (p < 0.05). HPLC analysis showed a fast cyclization of the probe (half-life t1/2 < 1h) to form cyclized products. The formation of GdNPs after caspase-3 activation confirmed by DLS and TEM. In vitro, apoptotic rASCs demonstrated significant, ~50% shortening of T1-relaxation times after incubation with C-SNAM compared to viable rASCs, while T1-times after exposure with the control probe were not significantly different. In vivo, apoptotic MASI showed significantly lower T1-relaxation times compared with viable MASI at 30 minutes after C-SNAM intra-articular injection. Bioluminescent imaging confirmed cellular apoptosis of C-SNAM enhancing rASC implants.

CONCLUSION We present a novel approach for non-invasive, high-resolution in vivo detection of stem cell apoptosis with a novel caspase-sensitive contrast agent for MR imaging. This new imaging biomarker could be applied to a wide variety of stem cell therapies, facilitate optimizations of MASI strategies, and ultimately improve successful tissue regeneration outcomes.

CLINICAL RELEVANCE/APPLICATION The described novel MR contrast agent, a strong candidate for clinical translation, could improve MR evaluations of stem cell transplants and direct patients with failed MASI to repeated interventions.

SSG08-04 Fluorescence Molecular Imaging of Myeloperoxidase in Irritant Contact Dermatitis and Bacterial Cellulitis Benjamin Pulli MD (Presenter): Nothing to Disclose , Cuihua Wang PhD : Nothing to Disclose , Gregory R. Wojtkiewicz MSc : Nothing to Disclose , Anning Li MD : Nothing to Disclose , Yue Wu : Nothing to Disclose , John Chen MD, PhD : Research Grant, Pfizer Inc PURPOSE

Myeloperoxidase (MPO) is an important oxidative enzyme stored in neutrophil granules. It is crucial for defense against pathogens but also contributes to tissue damage in inflammation. We sought to develop a molecular imaging probe sensitive and specific for MPO that is suitable for fluorescence imaging applications.

METHOD AND MATERIALS Ten female C57BL/6J (wildtype) mice and 3 MPO-knockout mice were either treated topically with 0.08 μmoles phorbol 12-myristate 13-acetate (PMA) on one hindpaw and with vehicle on the other to induce irritant contact dermatitis, or injected subcutaneously with 108 colony forming units of streptococcus pneumonia (SPn) to induce bacterial cellulitis. 6 hours after induction, mice were injected with the MPO sensor or a non-specific control sensor. Extracellular DNA in cellulitis was visualized with Sytox Green. Mice were imaged using a fluorescence reflectance imaging system (Olympus OV-110).

RESULTS Sensitivity to MPO was tested first in vitro by embedding the MPO sensor together with and without MPO in matrigel. A linear increase in signal is seen only in the presence of MPO (figure, A). In vivo, increased fluorescent signal was detected with dermatitis on the hindpaws of wildtype mice injected with MPO sensor (130.5±8.2 for PMA vs. 34.4±14.9 relative fluorescent units (RFUs) for vehicle, P<0.01, figure, B+C). In MPO-knockout mice injected with MPO sensor, and in wildtype mice injected with control sensor, no signal increase was detectable (36.9±13.8 and 50.13±10.0 for PMA vs. 43.9±15.2 and 28.4±9.4 RFUs for vehicle, P>0.05, figure, B+C). In wildtype mice induced with bacterial cellulitis, increased MPO specific signal was found in the hindlimb (212.5±22.9 for SPn vs. 49.4±15.5 RFUs for vehicle, P<0.001, figure, D). Sytox green signal revealed extracellular DNA in the inflamed area consistent with neutrophil extracellular trap formation, and MPO and DNA co-localized (figure, D).

CONCLUSION The results of this proof-of-concept study reveal that our novel fluorescent MPO sensor can specifically detect MPO activity in vivo at relevant biological concentrations. This was validated in two murine disease models. Neutrophil extracellular trap formation can be imaged by co-injection of MPO-sensor and Sytox Green.

CLINICAL RELEVANCE/APPLICATION Upon translation, MPO fluorescence molecular imaging could be used in perioperative as well as endoscopic settings (e.g., assessment of activity of inflammatory bowel disease).

SSG08-05 Role of F-18 FDG PET/CT in Differentiating Findings of Sarcoidosis versus Malignancy Sikandar Mohd Shaikh DMRD (Presenter): Nothing to Disclose PURPOSE

To review F-18 FDG PET/CT findings of Sarcoidosis mimicking malignancy

METHOD AND MATERIALS

F-18 FDG PET/CT scans in which Sarcoidosis was misinterpreted as malignancy were included. Sarcoidosis was confirmed by biopsy or surgery. F-18 FDG PET/CT finding was retrospectively evaluated. The maximum standardized uptake value (SUVmax) of the primary tumors and TB mimicking malignancy were measured.

RESULTS 50 cancer patients (11 for initial staging and 14 for restaging) and 14 Sarcoidosis patients without any malignancy were included (M:F=17:13, age 45±13). Sarcoidosis involved lung (n=17), cervical (n=10), mediastinal (n=5) and abdominal (n=5) nodes, bowel (n=1), adrenal gland (n=1) and pleura (n=1) in the 32 patients. Sarcoidosis caused false positive reading in 9 cases out of 11 staging cases leading to overstaging, 12 out of 14 restaging cases, and 7 patients without any malignancy, 4 falsely considered to have lung cancer and 3 abdominal malignancy. TB involved contralateral supraclavicular node (SCN) in 5 of 7 patients with breast cancer and right SCN in 4 of 7 patients with abdominal malignancy. In staging PET/CT, the mean SUVmax of the primary tumor was 5.0±3.6 (2~11.4), while that of Sarcoidosis considered as metastasis was 4.5±2.4 (2.0~6.5) in lung and 5.6±3.3 (2.4~8.9) in lymph node. In restaging PET/CT, the SUVmax of TB considered as recurrence was 2.8±0.8 (2.2~4.3) in lung and 4.8±2.3 (2.2~8.0) in lymph node. The mean SUVmax of Sarcoidosis mimicking malignancy was 3.7±1.3 (range 2.2~4.7) in lung and 6.1±3.3 (3.4~9.7) in abdomen.

CONCLUSION

Sarcoidosis mimicked primary cancer, metastasis or recurrence on FGD PET/CT, and led to upstaging in majority of cancer patients. SUV was not useful in discrimination. When FDG uptake is seen in contralateral SCN in breast cancer patients, and right SCN in abdominal malignancy patients, Sarcoidosis should be considered as differential diagnosis

CLINICAL RELEVANCE/APPLICATION PET-CT HAS MANY MIMICKS IN RELATION TO NEOPLASTIC LESIONS WHICH ARE SOMETIMES VERY DIFFICULT TO DIFFERENTIATE.

SSG08-06 Biochemical Cartilage Damage in Dependence on Inflammatory Severity in Rheumatoid Arthritis Falk Roland Miese MD (Presenter): Nothing to Disclose , Anja Lutz : Nothing to Disclose , Benedikt Ostendorf : Nothing to Disclose , Christian Rubbert MD : Fellowship funded, Koninklijke Philips NV , Gerald Antoch MD : Speaker, Siemens Medical AG Speaker, Bayer AG Speaker, BTG International Ltd , Christoph Schleich : Nothing to Disclose PURPOSE To assess cartilage damage measured by delayed gadolinium-enhanced magnetic resonance (MR) imaging of the cartilage (dGEMRIC) of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA) in dependence on joint inflammation severity.

METHOD AND MATERIALS 43 patients with rheumatoid arthritis (age 52.9±14.5 years, range:18-77 years; disease duration 2.9±4.9 years, range:<0.5-19 years; DAS28 3.7±1.5) who received 3T MRI scans of metacarpophalangeal joints of second and third finger and fulfilled the ACR/EULAR classification criteria were included in this study. Cartilage alterations were assessed by dGEMRIC of MCP2 and 3. The severity of synovitis was scored according to RAMRIS criteria (range:0-3) by two readers in consensus. C-reactive protein (CRP) levels and Disease Activity Score of 28 joints (DAS28) were recorded at the day of MRI. Spearman correlation of DAS(MCP2/3) and RAMRIS were calculated. Each patient's MCP2 and 3 were dichotomized into the joint with more severe synovitis versus the joint with less severe synovitis for paired Wilcoxon test of dGEMRIC index.

RESULTS dGEMRIC index of MCP with more severe synovitis was 369 msec±137, dGEMRIC index of MCP with less severe synovitis was 421msec±129. RAMRIS synovitis score of the joint with more severe synovitis was 2.51 (range:1-3), synovitis score of the joint with less severe synovitis was 1.86 (range:0-3). There was a significant difference of dGEMRIC index between the dichotomized MCPs (p=0.0001). The median of difference was 47.12, CI [16.6; 62.76]. There was a moderate correlation between dGEMRIC index and RAMRIS synovitis grading of the joint with more severe synovitis (r=0.5;p<0.05). The spearman rho showed a weak correlation between dGEMRIC index and RAMRIS synovitis of the joint with less sever synovitis (r= 0.33;p <0.05).

CONCLUSION

These data concur with the concept that inflammation and synovitis are associated with cartilage damage. In dichotomous analysis there is a different inflammation between MCP 2 and 3 in individual patients. The joint with more severe synovitis demonstrates a significantly lower dGEMRIC index representing a higher degree of cartilage destruction.

CLINICAL RELEVANCE/APPLICATION

The degree of cartilage damage correlates with inflammation severity in the particular joint supporting the concept that next to general inflammation in RA there is a local inflammatory cascade partly independent of systemic inflammation.

SSG08-07 Nanoconjugates as Targeted Agents for Molecular Ultrasound and Fluorescence Imaging Diagnosis and Staging of Uveitis and as Theranostic Agents Evan Charles Unger MD (Presenter): Shareholder, NuvOx Pharma LLC Shareholder, Microvascular Therapeutics , Paul Olson DPhil : Employee, Kypha , Stewart Williams DPhil : Nothing to Disclose , Edmund Marinelli DPhil : Employee, NuvOx Pharma, LLC , Delphine El Mehdi PhD : Research, Kypha Research, PGXL Laboratories , Jeremy S Touroo BS,MS : Nothing to Disclose PURPOSE Purpose: Uveitis is responsible for 10-20% of the cases of blindness in the U.S. and its economic impact is at least as great as diabetic retinopathy. The purpose of this research is to develop a targeted agent for molecular imaging of uveitis with ultrasound and fluorescence imaging that can be used for diagnostic purposes and also potentially as a theranostic for drug delivery.

METHOD AND MATERIALS Materials and Methods: Human retinal endothelial cells (HREC's) were grown in 2-D static and 3-D vascular mimetic phantoms. The HRECs were exposed to lipolysaccharide (LPS) and fluorescent antibodies were used to screen for expression of E-selectin, P-selectin, ICAM-1 and VCAM. Nanoconjugates (NCs) were prepared from a blend of phospholipid (DPPC and DPPE-PEG) using mechanical agitation to entrap perfluorobutane gas. The peptide DITWDQLWDLMK-OH was incorporated into the nanoconjugates via a PEG linker attached to lipids at a mole ratio = 1%. The peptide has a 4 nM KD for murine and human E-selectin. DiI was also incorporated into the NCs. Particle sizing was performed by QELS. Imaging studies were performed with fluorescence and high frequency ultrasound (VEVO) in the 2-D and 3-D phantoms and in rats with uveitis induced by LPS (n = 5 per group).

RESULTS Results: E-selectin was markedly upregulated in inflamed HREC's, >> than the other epitopes. The mean size of the NCs was < 1-micron. In vitro imaging showed marked accumulation of NCs on inflamed HRECs in conditions of flow; NCs bearing sham peptides showed no binding. The NCs were accumulated intracellularly by the inflamed HRECs. In vivo fluorescence and US imaging showed strong signal in inflamed eyes of the rats and no uptake in controls. Ex vivo study of the rat's eyes showed intracellular uptake of NCs by inflamed retinal endothelial cells and adjacent macrophages.

CONCLUSION Conclusion: NCs bearing this peptide are a promising agent for molecular ultrasound and fluorescence imaging of uveitis with strong binding to both human and rat/murine epitopes of E-selectin. Intracellular uptake of NCs by inflamed endothelial cells suggests theranostic potential as a platform for drug delivery. CLINICAL RELEVANCE/APPLICATION Because NCs work with both ultrasound and fluorescence and target a molecular marker of inflammation, NCs hold potential for better diagnosis and staging of uveitis. Intracellular uptake of NCs by inflamed cells shows potential for drug delivery.

SSG08-08 Multispectral Optoacoustic Tomography (MSOT) for Therapy Monitoring of Arthritis Reinhard Meier MD, PhD (Presenter): Nothing to Disclose , Nicolas Beziere : Nothing to Disclose , Claudio von Schacky : Nothing to Disclose , Moritz Wildgruber MD, PhD : Nothing to Disclose , Ernst J. Rummeny MD : Nothing to Disclose , Vasilis Ntziachristos PhD : Stockholder, iThera Medical GmbH PURPOSE

We investigated the use of multispectral optoacoustic tomography (MSOT) in a murine model to monitor therapy effects of arthritic inflammation in vivo through an L- and P-selectin targeting contrast agent.

METHOD AND MATERIALS

This preclinical imaging study was performed using multispectral optoacoustic tomography (MSOT) able to record the optoacoustic signal detected by a cylindrically focus 64-elements transducer after illumination by a tunable pulsed laser in the near infra-red range (680-900 nm), yielding transverse images of entire mice in real time. A polyglycerol-sulfate grafted with near-infrared fluorophore was used (dPGS-ICG), allowing highlighting of the expression of L- and P-selectins, directly correlating to the state of inflammation of the joint and surrounding tissue. In twenty mice we induced arthritis by injection of collagen in one leg while keeping the other leg untouched as a healthy reference. These mice underwent MSOT and MR imaging at day 5, 35 and 42 after arthritis induction and simultaneous therapy onset. 10 mice were allocated to the therapy group receiving prednisolone and methotrexate, while 10 other mice served as controls treated with PBS. Data was processed using a model-based image reconstruction process followed by a least-square method spectral fitting. Clinical assessment of arthritis as well as ex vivo planar fluorescent imaging was used to validate the results obtained by imaging.

RESULTS MSOT allowed clear identification of the probe over the anatomical signal. MSOT signal intensity directly and quantitatively correlated to the advancement of the disease in the joint. The findings matched well with MR imaging showing Gadolinium infiltration in the synovial fluid. Arthritic inflammation was significantly lower in the therapeutic compared to the control group (p<0.05) on day 35 and 42 after therapy onset as measured with MSOT and confirmed by MR imaging, clinical examination and histopathology.

CONCLUSION MSOT allows for therapy monitoring of arthritic inflammation. In the future, we see this imaging method may help to determine treatment response in an early state. For non-responders earlier change in therapy strategy could lead to reduction of unnecessary side effects.

CLINICAL RELEVANCE/APPLICATION

Given the current development of the MSOT technology, it is expected that similar approaches will rapidly be translated in the clinic as a fast and relatively cheap staging procedure.

SSG08-09 A Role of the 18-FDG-PET/CT in the Assessment of Sepsis of Uncertain Origin Jiri Ferda MD, PhD (Presenter): Nothing to Disclose , Eva Ferdova MD : Nothing to Disclose , Jan Baxa MD, PhD : Nothing to Disclose PURPOSE To assess a role of the hybrid imaging with 18-FDG-PET/CT in detection of the cause of sepsis of uncertain origin

METHOD AND MATERIALS In the sample of 42 adult patients (23 males, 29 females, mean age 43,7 y. ranging 24 - 81 y.), 18-FDG-PET/CT was referred due to the concurrent or recurrent septic state. The changes in the glucose metabolism related to the suspected site of infection were searched. All examinations were conducted after intravenous application of 18F-fluorodeoxyglucose in the dose of 4 MBq/kg of body weight and 60 minutes of radiopharmaceutical accumulation, all PET/CT scans were performed using three-ring-sixteen-slice system (Biograph 16 HR, Siemens, Knoxville, TN, USA) with the intravenous application of 80 ml of iodine contrast material with sub-millimeter spatial resolution. In all patients was investigated microbial infection agens using blood samples or the assessment of specimen taken from the site of focal infection.

RESULTS The focal finding allowing detection of the origin of the septic state was found in 39 of 42 pts. (92.8%), three cases remained with undetermined cause of sepsis. Those most frequent sites of the hidden infection were found: spondylodiscitis in 30.7% (12/39), followed by musculoskeletal infection in 25.4% (10/39) including pyogenous arthritis (3 cases), psoatic abscess (2 cases) or joint prosthesis infection (5 cases); cardiovascular infection in 23.1% (9/39) including endocarditis (3 cases), pericarditis (one case), mycotic aneurysm (3 cases) and vascular prosthesis infection (2 cases). Other, less frequent causes of septic or septic-like state were gastrointestinal inflammation in 4 cases, lung infection in 3 cases and one case of Hodgkin lymphoma. The proven bacterial agens was in 37 cases - 16 cases of staphylococcal (including 7 cases of methiciline resistant proven bacterial agens was in 37 cases - 16 cases of staphylococcal (including 7 cases of methiciline resistant streptococcus aureus and 5 cases of methiciline sensitive streptococcus aureus); 6 cases of streptococcal; 13 cases of Gramm negative bacterial and 2 cases of mycobacterial infection.

CONCLUSION

18-FDG-PET/CT reached the sufficient efficiency in detection of the origin of sepsis in patient with uncertain site of infection; the spondylodiscitis is the most frequent finding in septic state.

CLINICAL RELEVANCE/APPLICATION

18-FDG-PET/CT is reaching the positive results in more than 90% cases of referred patients allowing the subsequent targeted therapy.

MIS-TUA Molecular Imaging Tuesday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Tue, Dec 2 12:15 PM - 12:45 PM Location: S503AB

Participants Moderator Peter Herscovitch MD : Nothing to Disclose Moderator Charles Emmet Stout MD, PhD : Nothing to Disclose

Sub-Events MIS129 Imaging Somatostatin Receptor Subtype 2 in High-Grade Glioma with [68Ga]DOTATOC and [68Ga]DOTANOC PET/CT (Station #7) Aida Karoliina Kiviniemi MD (Presenter): Nothing to Disclose , Maria Gardberg MD : Nothing to Disclose , Marko Pesola : Nothing to Disclose , Janek Frantzen MD, PhD : Nothing to Disclose , Riitta K. Parkkola MD, PhD : Nothing to Disclose , Ville Vuorinen MD, PhD : Nothing to Disclose , Tuula Tolvanen : Nothing to Disclose , Jarkko Johansson : Nothing to Disclose , Jukka Kemppainen : Nothing to Disclose , Anne Roivainen : Nothing to Disclose , Heikki Ralph Minn MD, PhD : Support, Bayer AG PURPOSE Somatostatin receptor type 2 (sstr2) targeted radionuclide therapy is a potential new therapeutic strategy in high-grade glioma (HGG). The purpose of this study was to detect sstr2 expression in HGG with [68Ga]DOTATOC or [68Ga]DOTANOC PET/CT and to investigate the effect of blood-brain barrier (BBB) integrity on tumor tracer uptake with T1-weighted gadolinium enhancement on MRI (T1gad).

METHOD AND MATERIALS 27 patients with primary or recurrent HGG underwent dynamic [68Ga]DOTATOC or [68Ga]DOTANOC PET/CT prior to surgery. Maximum standardized uptake values (SUVmax) were calculated and Logan plot was applied to measure receptor binding potential (BP). PET data was correlated to tumor sstr2 immunohistochemistry. Tumor volume concordance between PET (40% SUVmax threshold) and T1gad was assessed by Dice similarity coefficient (DC). Finally, sstr2 expression was correlated to molecular biomarkers with a prognostic value such as mutated IDH1.

RESULTS Tumor SUVmax significantly correlated with T1gad volume (r=0.90, p CONCLUSION [68Ga]DOTATOC and [68Ga]DOTANOC uptake and binding to sstr2 in HGG is highly dependant on BBB disruption evaluated by T1gad on MRI. However, tracer uptake cannot be predicted by sstr2 immunohistochemistry which together with relatively low tumor SUVmax suggests limited feasibility of HGG to sstr2 targeted radionuclide therapy.

CLINICAL RELEVANCE/APPLICATION Sstr2 expression in HGG corresponds to biomarkers associated with favorable prognosis. However, sstr2 expression in HGG cannot be predicted by [68Ga]DOTATOC or [68Ga]DOTANOC PET/CT.

MIS132 Role of F-18 FDG PET-CT in Assessment of Patients with Suspected Infection or Inflammatory Conditions (Station #10) Sikandar Mohd Shaikh DMRD (Presenter): Nothing to Disclose PURPOSE

The objective of this study was to highlight the clinical significance and role of FDG PET-CT in assessment of patients with suspected infection or inflammatory condition. patients with suspected infection or inflammatory condition.

METHOD AND MATERIALS A total of 22 pts (59.6 ± 15.1 years old, M/F=14/8) with suspected infection and inflammatory condition from clinical manifestations and blood tests were retrospectively studied. FDG PET-CT was performed on these patients to localize infection or inflammatory sites. PET-CT findings were evaluated in relation to results of blood tests (C-reactive protein (CRP), white blood cell count (WBC)), treatment, and prognosis.

RESULTS 5 pts (22.7%) showed negative findings on FDG PET-CT. All these patients recovered with conservative antibiotic treatment and favorable prognosis except one patients (one with viral encephalitis who had severe neurological sequelae ). 16 pts (75%) showed positive findings suggesting infection or inflammation in various regions: bone and soft tissue, 4; colon, 2; mediastinum, 2; lung, 2; heart and pericardium, 2; retroperitoneum,1 gall bladder, 1; kidney,1; vascular graft,1, One patient (2.3%) showed positive finding suggesting not infection but malignant lymphoma and was diagnosed with diffuse large B cell lymphoma subsequently. In PET-positive pts, surgical treatments, abscess drainage, or removal of pace maker lead were done in 5 pts. In PET positive patients2 pts had died due to multiple organ failure, Remaining 15 pts recovered by appropriate surgical and medical treatment. In PET-negative and PET-positive pts, CRP (mg/dl) was 9.0±9.0 and 8.6±7.6, WBC (/μl) was 8600±3300 and 10000±6600, showing no significant difference.

CONCLUSION

FDG PET-CT was useful in initial assessment of patients with suspected infection or inflammatory condition, providing important information regarding location and severity of the disease. PET-negative pts tended to have mild disease however, presence of PET-negative severe disease such as viral encephalitis should be kept in mind.

CLINICAL RELEVANCE/APPLICATION

Thus FDG PET-CT is important tool in diagnosing the many infective foci in the body

MIS-TUB Molecular Imaging Tuesday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Tue, Dec 2 12:45 PM - 1:15 PM Location: S503AB

Sub-Events MIS134 Improved Tumor Enhancement with Nanoparticulate Contrast Agent in Computed Tomography by Saturation of Reticuloendothelial System (Station #7) Yun Jung Kim MD (Presenter): Nothing to Disclose , Kangtaek Lee : Nothing to Disclose , Bumsang Kim : Nothing to Disclose , Jin Hur MD : Nothing to Disclose , Byoung Wook Choi MD : Nothing to Disclose PURPOSE

To improve enhancement of tumor with a nanoparticulate contrast agent in computed tomography by pretreatment of liposome to saturate reticuloendothelial system (RES), which is expected to slow down the elimination of nanoparticulate contrast agent from the blood through RES.

METHOD AND MATERIALS We first determined the optimal time, amount, and particle size of liposome administration for saturation of RES and the optimal enhancement time point of tumor by a nanoparticulate contrast agent (pegylated gold nano particle; AuNP, 40nm). Lewis lung cancer cells (1 x 106) were inoculated to the thigh of C57BL/6 mice (n=6). Two weeks later after tumor fully had grown, the mice were divided into two groups, 1) liposome-treated group with injection of AuNP after 2 hours from liposome injection (150-400nm) to saturate RES (n=3) and 2) non-treated group with injection of AuNP only (n=3). Micro-CT scan was performed to include liver, spleen, and the tumor immediately before and 48 hours after AuNP injection. The mean increase of tumor enhancement was compared between two groups on the liver, spleen, and the tumor respectively. The immune suppression and recovery were followed by surveying gene expression of TNFα, IL-6, NOS, CD14, and histology of the liver and spleen in separate liposome-treated mice (n=3, 3 respectively).

RESULTS The enhancement of tumor was greater in liposome-treated group than in non-treated group (average 164.8 vs. 48.8). That of spleen was greater in non-treated group than in treated group (average 570.0 vs. 245.1). That of liver was similar between two groups (average 506.1 in treated group vs. 530.4 in non-treated group). The enhancement of tumor in treated group increased to 288% of that in non-treated group. The enhancement of spleen in treated group decreased to 46.9% of that in non-treated group. Decreased level of gene expression of TNFα, IL-6, NOS, and CD14 and decreased number and deformed shape of macrophages by RES saturation almost recovered in 2 weeks. CONCLUSION

RES saturation by liposome with a tolerable degree of immune suppression is feasible to improve tumor enhancement with nanoparticulate contrast agent.

CLINICAL RELEVANCE/APPLICATION It will provided the feasibility of reticuloendothelial saturation prior to administration of nanoparticulate contrast agent improving the efficacy with same amount of contrast agents or reducing the amount of administration maintaining same degree of enhancement.

MIS135 MR Imaging of Tumor Associated Macrophages In Pediatric Patients with Malignant Lymphomas and Sarcomas (Station #8) Tarsheen Sethi MBBS (Presenter): Nothing to Disclose , Jessica Donig BA : Nothing to Disclose , Maryam Aghighi MD : Nothing to Disclose , Samantha Holdsworth PhD : Nothing to Disclose , DITA GRATZINGER : Nothing to Disclose , Heike E. Daldrup-Link MD : Nothing to Disclose , Florette Hazard : Nothing to Disclose , Raffi S. Avedian MD : Nothing to Disclose , Neyssa Marina MD : Nothing to Disclose , sandra luna-fineman MD : Nothing to Disclose PURPOSE Tumor associated macrophages (TAM) are key components of the tumor microenvironment with a role in the pathogenesis and progression of many tumors. The aim of our study was the clinical translation of a non-invasive technique for imaging TAMs in pediatric tumors based on ferumoxytol-enhanced Magnetic Resonance (MR) Scans, evaluating iron uptake as surrogate for macrophage content and correlating with histopathology.

METHOD AND MATERIALS 15 children and young adults with lymphomas (n=7) and sarcomas (n=8) underwent MR imaging at least 24 hours after intravenous injection of the iron oxide nanoparticle ferumoxytol. MR scans included STIR and T1-weighted SPGR sequences for anatomical assessment of iron uptake and T2* FSPGR and eFGRE sequences for quantitative assessment. Mean T2*-relaxation times of whole tumors were calculated. In addition, tumor regions with intracellular and extracellular iron were differentiated based on STIR and T1-weighted SPGR MR Scans. Histopathology correlation was based on 11 biopsy and 3 tumor resection samples evaluated by Prussian blue stain and macrophage immunohistochemistry markers CD-68 and CD-163. Macrophage content was assessed semi-quantitatively as low, intermediate and strong CD68 and CD163 staining by manual slide review by two pathologists. T2*-relaxation times of whole tumors and tumor areas were correlated with macrophage quantities on histopathology. Tumor macrophage heterogeneity was also assessed on MR Scans and compared with histopathology using McNemar's test.

RESULTS The mean T2* relaxation times were 4.53 ms and 6.15 ms for sarcomas and lymphomas respectively. All tumors demonstrated presence of macrophages by immunohistochemistry. Sarcomas showed a heterogeneous distribution of TAM on pathologic evaluation and heterogeneous iron uptake on MR scans, while six out of seven lymphomas showed homogenous TAM distribution and iron uptake. A McNemar's test revealed no significant difference in assessment of homogenous or heterogenous TAM distribution by histology or imaging (p value =1.00).

CONCLUSION Our study represents the clinical translation of a non-invasive method for TAM imaging based on ferumoxytol enhanced- MR scans with histopathology correlation.

CLINICAL RELEVANCE/APPLICATION

The presented ferumoxytol enhanced-MR based technique is immediately clinically applicable and allows for a non-invasive imaging of TAM, a potential marker for prognosis and immunotherapy response assessment.

MIS136 Role of Tumor Texture Analysis on CT Image and Tumor Metabolism Measured by FDG-PET in the Management of Non-small Cell Lung Cancer Patients (Station #9) Koichi Hayano MD (Presenter): Nothing to Disclose , Naveen Kulkarni MD : Nothing to Disclose , Fang Tian MD : Nothing to Disclose , Dushyant V. Sahani MD : Research Grant, General Electric Company PURPOSE Aerobic glycolysis in cancer cells involves elevated glucose uptake. On the other hand, heterogeneity in the structure or blood supply is a well recognizes feature of malignancy. The purpose of this study is to compare computed tomography texture analysis (CTTA) with tumor metabolism measured by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and survival in non-small cell lung cancer (NSCLC) treated with combined therapy of nanoparticle albumin-bound paclitaxel (nab-paclitaxel), calboplatin and bevacizumab.

METHOD AND MATERIALS In the phase II clinical trial, 35 patients (17 M / 18 W; median age: 64.0 years) with unresectable or metastatic NSCLC treated with nab-paclitaxel, calboplatin and bevacizumab were enrolled. Median follow-up time was 12.5 months. FDG-PET and non-contrast enhanced (CE) CT were performed before the therapy. Tumor texture parameters including mean gray intensity (MGI), Entropy, mean of positive pixels (MPP) were measured on non-CECT images by a texture analysis software (TexRAD, Somerset, UK), where the filtration (spatial scale filter, SSF) extracted features of medium texture scale (SSF=4 mm in radius). Correlations of texture parameters with SUVmax were investigated, and those parameters were compared with overall survival (OS) using Cox regression and Kaplan-Meier analysis.

RESULTS MGI and MPP showed a negative correlation with SUVmax (R=-0.472, P=0.008; R=-0.485, P=0.006; respectively). In univariate Cox regression analysis, SUVmax, MGI, MPP and Entropy showed significant correlations with OS (P=0.03, P=0.02, P=0.04, P=0.0008, respectively). In Kaplan-Meier analysis, higher MGI, MPP, lower SUVmax and Entropy associated with favorable OS (P=0.0008, P=0.0009, P=0.01, P=0.005, respectively). In multivariate analysis, Entropy was identified as an independent prognostic factor of NSCLC (P=0.01; hazards ratio, 4.14; 95% CI, 1.23-25.53) in comparison with SUVmax, MGI, and MPP.

CONCLUSION Pre-therapeutic tumor texture parameter on non-CECT can serve as a predictive imaging biomarker reflecting tumor metabolism and survival in NSCLC patients treated with nab-paclitaxel, calboplatin and bevacizumab.

CLINICAL RELEVANCE/APPLICATION CT texture analysis can be a widely applicable noninvasive biomarker for predicting survival in non-small cell lung cancer patients, and it would help select an optimal therapy for those patients.

MIS137 Fluorescence Molecular Tomography of DiR-labeled Mesenchymal Stem Cells Implants in Osteochondral Defects of Rabbit Knees (Station #10) Markus Thomas Berninger MD : Nothing to Disclose , Pouyan Mohajerani : Nothing to Disclose , Bernhard Haller : Nothing to Disclose , Vasilis Ntziachristos PhD : Stockholder, iThera Medical GmbH , Reinhard Meier MD, PhD : Nothing to Disclose , Tobias D. Henning MD (Presenter): Nothing to Disclose PURPOSE FMT-XCT is a 3D imaging technique that combines the high sensitivity of fluorescence molecular tomography (FMT) with the high resolution of X-ray CT. The purpose of this study was to establish an intermediate sized animal model in a rabbit for FMT-XCT stem cell tracking in the scenario of osteochondral defect repair.

METHOD AND MATERIALS Mesenchymal stem cells (MSC) were isolated from the bone marrow of New Zealand White rabbits. Then, cells were labeled with the near infrared lipophilic carbocyanine dye DiR (1.25 - 20 μg). Induction of apoptosis and toxicity were assessed by Caspase-3/-7-, Trypan Blue- and XTT-testing. Chondrogenic potential was assessed in pellet cultures (n=3) by measurement of glycosaminoglycans. Labeled cells and unlabeled controls (n=3) underwent FMT-XCT imaging before and after chondrogenic differentiation. Then, osteochondral defects (3.8 x 3.5 mm) were created surgically in the femoral condyle of rabbit knees (n=6) and 200.000 unlabeled and labeled MSC were implanted in a fibrin clot and imaged at FMT-XCT. Statistics were performed using a t-test.

RESULTS Labeling of MSC with DiR resulted in a strong, significant and dose-dependent fluorescence signal at all concentrations on FMT images (p0.05). Thus, a labeling concentration of 5 �g DiR was chosen for animal studies. FMT-XCT of labeled MSC after implantation in osteochondral defects showed a strong and significant signal on FMT (p CONCLUSION MSC could be labeled with DiR without toxic side effects or impairment of chondrogenesis. Labeled cells showed a significant fluorescence signal in vitro and were well depicted by FMT-XCT after implantation in osteochondral defects in a rabbit animal model of cartilage repair.

CLINICAL RELEVANCE/APPLICATION The use of FMT-XCT in an intermediate sized animal model offers high sensitivity and 3D-image detail. Clinical translation of FMT-XCT could be valid in human follow-up studies in tissue engineering.

MIS138 Optically-assisted Needle Guidance to Differentiate Bile from Liver Parenchym and Blood (Station #11) Mohammad Eghtedari MD, PhD : Nothing to Disclose , Cherng Chao MD, JD (Presenter): Nothing to Disclose , Saharnaz Baghdadchi : Nothing to Disclose , Robert Frederick Mattrey MD : Nothing to Disclose , Sadik Esener : Nothing to Disclose PURPOSE To determine if an optical core biopsy needle could be designed from fiber optic cables to differentiate bile from liver parenchyma and blood.

METHOD AND MATERIALS We developed a prototype fiber sensor based needle consisting of two optical fiber cables with 200 um core diameter and 0.22 numerical aperture assembled in a standard 15 cm 20 gauge. One of fibers was connected to a light source composed of two red and green color laser diodes with a microcontroller to modulate the source lights. The other fiber was used to transmit the backscattered photons detected at the tip of the needle to the detector. Three distinct wavelengths of 520, 630 and 700 nm were selected to determine the location of needle tip (Figure 2). Based on the optical properties of the tissue like absorption coefficient, scattering coefficient, and the anisotropy factor at the selected wavelengths, an algorithm was developed for determining the location of the needle tip using the detected backscattered light. We tested the designed optical core biopsy needle using in a cadaveric poultry model composed of blood, bile and liver parenchyma.

RESULTS The measured intensity ratio of red to green light in blood was consistently more than 20, while this ratio for liver parenchyma was between 1.2 and 2. The measured intensity ratio of red to green light in bile was less than 0.5. These substantially different intensity ratios allowed easy differentation of bile from blood and liver parenchyma.

CONCLUSION An optical core biopsy needle designed and implemented using fiber optic cables could successfully differentiated bile from liver parenchyma and blood in cadaveric poultry specimens.

CLINICAL RELEVANCE/APPLICATION

Our optical fiber based biopsy needle could be used in percutaneous hepatobiliary procedures to idenitfy the needle tip position based on the optical properties of tissue at the needle tip.

SSJ14 Molecular Imaging (GI/Liver)

Scientific Papers NM MI CT GI AMA PRA Category 1 Credits ™: 1.00 ARRT Category A+ Credit: 1.00 Tue, Dec 2 3:00 PM - 4:00 PM Location: S504CD

Participants Moderator Vikas Kundra MD, PhD : License agreement, Introgen Therapeutics Inc Moderator Lawrence H. Schwartz MD : Nothing to Disclose

Sub-Events SSJ14-01 Angiotensin Receptor Blockade Causes Measurable Increases in Drug Delivery in Pancreatic Cancer Model as Measured by 18F-5fluorouracil and PET Alexander Ramos Guimaraes MD, PhD (Presenter): Speakers Bureau, Siemens AG Expert Witness, Rice, Dolan, Kershaw , Vidhya Kumar : Nothing to Disclose , Rakesh K. Jain PhD : Board of Directors, XTuit Pharmaceuticals Stockholder, XTuit Pharmaceuticals , Ciprian Catana MD, PhD : Nothing to Disclose , Hong Ren PhD : Nothing to Disclose , Yves Boucher PhD : Nothing to Disclose , Jacob M. Hooker PhD : Nothing to Disclose , Andrew Hoover PhD : Nothing to Disclose , Diego Santos Ferreira PhD : Nothing to Disclose PURPOSE Pancreatic ductal adenocarcinoma (PDAC) responds poorly to chemotherapy partly due to a collagen rich desmoplastic response that is a barrier to drug delivery. Recent studies, however, have demonstrated increased survival with FOLFIRINOX, a component of which is 5-fluorouracil. In addition, angiotensin receptor blockade (ARB) with Losartan ® has been shown to enhance the intratumoral penetration and efficacy of therapeutics in mice using in vitro techniques. The purpose of this study was to test the hypothesis that ARB leads to measurable increased drug delivery as evidenced by labeled 18F-5fluorouracil (5FU) using microPET in a mouse model of PDAC.

METHOD AND MATERIALS All experiments were approved by the local ethical review panel. Orthotopic tumors were generated by implanting 1mm3 chunks of AK4.4 spontaneously generated tumors (from a Ptfl-Cre/LSL-KrasG12D/p53Lox mouse model) into the pancreas of 6-8 week old FVB mice. Tumors were allowed to grow for 1 week prior to treatment. Animals were treated daily with an ip injection of 70mg/kg Losartan for 5 days. 18F-5FU was synthesized using novel, recently published approaches that produce increased yield. MicroPET studies were performed on a Triumph PET/CT Scanner. Orthotopic pancreatic tumor model mice were anesthetized using isoflurane and imaged in Treated-Control pairs. Dynamic PET images were acquired for 60 minutes, using a 18F-5FU tracer dose of 200 uCi per animal. CT scans for attenuation and anatomic coregistration were performed immediately following PET acquisition. ROI analysis was performed on dynamic co-registered images using Osirix ® with tumor time activity curves normalized to muscle. Statistical analyses compared both cohorts using a paired two tailed t-test.

RESULTS N=6 animals (3 pairs) were studied. Losartan treated animals demonstrated a mean % increase of 148% in drug delivery as measured by 18F-5FU PET that was statistically significant (p CONCLUSION ARB in a PDAC orthotopic model demonstrates reproducible, increased drug delivery using PET and labeled 18F-5FU. This method is easily translatable to humans suffering from PDAC.

CLINICAL RELEVANCE/APPLICATION With the improved survival in patients with pancreatic cancer following FOLFIRINOX, this technique could be translated to study novel targeted modulation of the tumor microenvironment concomitant with 5FU based therapies. therapies.

SSJ14-02 Estimation of Liver Function on Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging: Compare with T1 Mapping and the Quantitative Liver–Muscle Contrast Ratio Zhenpeng Peng (Presenter): Nothing to Disclose , Shiting Feng MD : Nothing to Disclose , Ziping Li MD, PhD : Nothing to Disclose PURPOSE To estimate the ability of T1 mapping of liver and the quantitative liver-muscle contrast ratio (Q-LMC) on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging for the estimation of liver function.

METHOD AND MATERIALS Institutional Review Board approval and written informed consent were obtained.94 patients underwent MRI with a 3.0T system before and at 20 minutes after Gd-EOB-DTPA administration.73 were Child-Pugh class A(CPA) ,14 were B(CPB) and 7 were C(CPC).T1 maps were acquired using three dimensional spoiled gradient echo sequences with two different flip angles (2 and 11 ) and a fixed TR/TE (4.4ms/1.2ms). Liver T1 values were obtained using a T1 processing tool (MapIT software). T1 relaxation time of liver and reduction rate of T1 relaxation time between pre- and post-contrast enhancement were measured. The quantitative liver-muscle contrast ratio (Q-LMC) was calculated using the signal intensities of the liver and erector spinae with fat-suppressed FLASH T1-weighted sequence images. The one-way anova and pearson correlation were used for comparisons between the 2 methods.

RESULTS Post-contrast T1 relaxation times of liver were significantly reduced. The reduction rate of T1 relaxation time in CPA/CPB/CPC were 77.6±8.4%,62.6±8.5%,50.7±12.5%. The difference between each group were significant (P<0.05). The increase Q-LMC in CPA/CPB/CPC were 59.4±8.5%,48.5±6.3%,46.2±6.2%. The difference between CPA/CPB and CPA/CPC were significant (P<0.05), but the difference between CPB/CPC was not significant(P>0.05).The pearson correlation coefficient of the reduction rate of T1 relaxation time and the Q-LMC were -0.648 and -0.526.

CONCLUSION

Both the T1 mapping of liver and the Q-LMC before and after Gd-EOB-DTPA administration can help estimate liver function. The reduction rate of T1 relaxation time was the better index of liver function than the Q-LMC.

CLINICAL RELEVANCE/APPLICATION

The reduction rate of T1 relaxation time was the better index of liver function than the Q-LMC.

SSJ14-03 Assessment of Aquaporins Function of Early-stage Liver Fibrosis Using Multi-B Diffusion-weighted MRI Qiu-Ju LI MD (Presenter): Nothing to Disclose , Jiahui Li MD : Nothing to Disclose , Bing Yu MD : Nothing to Disclose , Yu Shi PhD : Nothing to Disclose , Zhou-She ZHAO : Nothing to Disclose , Zi-Heng ZHANG : Nothing to Disclose , Qiyong Guo MD : Nothing to Disclose PURPOSE

To investigate the relationship between the ADC values and AQP expression, using a multiple b-value(multi-b) diffusion weighted magnetic resonancce imaging(DW MRI),with the histopathological and immunohistochemical tests as gold standard.

METHOD AND MATERIALS 24 rodent liver fibrosis models at different fibrotic stages were prepared in male Wistar rat for the experiment through thioacetamide injection thrice a week with another 6 intact as the control group. Both groups were performed MR measurements, on a 3.T scanner, before and after the injection of acetazolamide solution, an typical AQP inhibitor, used to inhibit the AQP1, AQP3 and AQP4 on hepatic tissue. For the MR protocol, besides the conventional T1WI and T2WI , a multi-b DWI was carried out with 18 b values selected from 0 to 4500 s/mm2(low-b: <200 s/mm2, mid-b: 300-1500s/mm2 and high-b: 1700-4500 s/mm2). The obtained multi-b DW images were post-processed through a newly developed tri-exponential model with low-b, mid-b, and high-b ADCs achieved. The output parametric maps were reviewed and analyzed blindly by two experienced observers with no histologic detail informed. The same layer of the harvested lobe were chosen for the routine HE staining, Sirius red staining of collagen, and AQP1 molecular pathology staining to determine the stage of liver fibrosis and the AQP1 expression level. Liver fibrosis was evaluated according to the Metavir scoring system.

RESULTS The AQP1 expression in the liver endothelial cells significantly increased with aggravation of liver fibrosis from normal to early stage fibrosis. The mean high-b ADC value of S2 was significantly higher than S1, both higher than S0 (P<0.05), which was in accordance with the result of immunohistochemical tests. At S1, the high-b value post inhibitors injection had a significant decrease (>30%), and 20% higher than S2. However, the inhibition tests were negative at S0.

CONCLUSION

It was demonstrated in this study that the severity of liver fibrosis is positively correlated with the AQP1 expression and the multi-b DW MRI technique was capable to detect the S1 stage liver fibrosis.

CLINICAL RELEVANCE/APPLICATION

AQP multi-b DWI molecular imaging is a promising tool for early diagnosis of liver fibrosis.

SSJ14-04 Prognostic Value of Simplified Dual-timepoint FDG-PET/CT in Pancreatic Cancer: Comparison to Routine SUV Measurements Freimut Juengling MD, PhD (Presenter): Nothing to Disclose , Christian Bieg MD : Nothing to Disclose , Ralph Peterli MD : Nothing to Disclose , Ines Valenta : Nothing to Disclose , Markus Von Flue MD : Nothing to Disclose , Markus Gass MD : Nothing to Disclose PURPOSE

To evaluate the prognostic value of early dual-timepoint kinetics in pancreatic malignancies as compared to routine single SUV measurements alone.

METHOD AND MATERIALS In a prospective analysis of 55 consecutive patients with histological or cytological diagnosis of pancreatic cancer, scheduled for FDG-PET/CT, dual-timepoint PET/CT was performed at 60 min. and 90 min. after application of FDG. Images were fused with routine MRI and accordingly, lesional SUV min, SUVavg and SUVmay were respectively measured for each timepoint. Regional changes in SUVs were calculated as previously described. Patients were followed-up for 12-70 months, with death or survival as primary endpoint. For analysis of prognostic significance on survival, patients were assigned to two pairs of groups, according to regional changes in SUV exceeding a cut-off of 3.5 in SUVmax or of 11% change in SUV measurements and Kaplan-Meier survival curves were plotted using MedCalc software. Survival curves were compared using the logrank test.

RESULTS Comparison of survival rates between groups based on SUVmax >= 3.5 vs. SUVmax < 3.5 (a cutoff proposed by several groups, eg. Hu et al. 2013) did not result in a significant difference between groups (logrank test, P=0.9298), while a regional SUV increase of more than 11% differentiated between a high-mortality group (36% survival probability at 24 months; 22% at 36 months) and a low-mortality group (86% survival probability at 24 months; 68% at 36 months, P=0.0041, logrank test))

CONCLUSION

Dual timepoint FDG-PET/CT performed as early as 30 minutes after the initial study adds significant prognostic information to standard PET evaluation based on single SUV measurements and differentiates between a high-mortality group and a low-mortality group at 24 and 36 months after initial diagnosis.

CLINICAL RELEVANCE/APPLICATION The proposed dual-timepoint PET/CT imaging protocol adds significant, prognostic information on survival probability, as compared to standard imaging and SUV measurements. The additional time and effort, consisting in 5 minutes of additional scanning immediately after completion of routine protocols, is minimal and fits perfectly into the existing, clinical workflow.

SSJ14-05 Transcriptomic and Immunohistochemical Profiling of Pancreatic Ductal Adenocarcinoma: Search for Functional Imaging Biomarkers Stephanie Kay Carlson MD (Presenter): Royalties, Medspira, LLC , Alan Penheiter PhD : Nothing to Disclose , Claire E. Bender MD : Nothing to Disclose , Sibel Erdogan : Nothing to Disclose , Stephen J. Murphy PhD : Nothing to Disclose , Steven N. Hart PhD : Nothing to Disclose , Joema Felipe Lima : Nothing to Disclose , Fariborz (Fred) Rakhshan Rohakhtar : Nothing to Disclose , Daniel R. O'Brien : Nothing to Disclose , William Bamlet MS : Nothing to Disclose , Ryan E. Wuertz : Nothing to Disclose , Thomas C. Smyrk : Nothing to Disclose , Fergus J. Couch PhD : Nothing to Disclose , George Vasmatzis PhD : Nothing to Disclose PURPOSE

Imaging plays an important role in the management of patients with pancreatic ductal adenocarcinoma (PDAC); however, the ability to reliably detect early stage tumors and accurately identify the true extent of disease preoperatively is severely limited with current anatomical diagnostic imaging techniques (computed tomography, magnetic resonance imaging, endoscopic ultrasound). We employed a target-centric strategy to identify transporter proteins upregulated in PDAC versus normal pancreas as potential targets for a new functional imaging probe to complement existing anatomical imaging approaches.

METHOD AND MATERIALS

We have performed transcriptomic (gene expression) profiling using laser capture microdissection, microarray and RNAseq on histologically-confirmed primary PDAC tumors and normal pancreas tissue from 33 patients, including five patients whose tumors were isoattenuating to normal pancreas and not visible on CT. RNAseq data were analyzed as gene normalized counts using the mapped reads per kilobase per million mapped reads (RPKM) method. Target expression at the protein level was confirmed with immunohistochemistry on tissue microarrays from 94 PDAC patients. All studies on human specimens were approved by our Institutional Review Board. RESULTS

Our search has identified at least 10 candidate transporter proteins upregulated in PDAC versus normal pancreas. Thus far, the best potential imaging target identified was SLC6A14, a neutral and basic amino acid transporter. SLC6A14 was overexpressed at the transcriptional level in all patients and expressed at the protein level in 95% of PDAC tumors.

CONCLUSION

SLC6A14 merits further investigation as a candidate transporter for functional imaging of PDAC.

CLINICAL RELEVANCE/APPLICATION

A new functional imaging probe that selectively targets PDAC with high sensitivity could transform patient management by allowing earlier detection and surgical intervention, and improving preoperative staging of disease.

SSJ14-06 Pre-treatment FDG-PET/CT Predicts Distant Relapse Following Percutaneous Ablation for Colorectal Liver Metastases James Franklin MA, MBBS (Presenter): Nothing to Disclose , Jean SZ Lee MRCP, MBBChir : Nothing to Disclose , Charles Dearman BA : Nothing to Disclose , Daniel Yiu Fai Chung MBBS, FRCR : Nothing to Disclose , Ewan Mark Anderson MBBCh : Nothing to Disclose , Fergus Vincent Gleeson MBBS : Alliance Medical Ltd Consultant PURPOSE

Percutaneous ablation has a role in the local treatment of colorectal liver metastases. Patients are typically selected for therapy based on technical, rather than biological, considerations. Pre-treatment techniques to allow improved patient selection for local therapy would be of clinical value. The aim of this study was to assess whether quantitative [18F]-FDG-PET/CT (PET/CT) was associated with patterns of disease relapse at 1 year.

METHOD AND MATERIALS This was a retrospective cohort study of 24 patients with solitary colorectal liver metastases, who underwent percutaneous ablation. All patients had a PET/CT scan prior to treatment. The presence of intra- or extrahepatic distant metastatic relapse at 1 year was determined by contrast-enhanced CT, and MRI or PET/CT where available. Patients with metastatic relapse were classified into oligometastatic or polymetastatic patterns of relapse; oligometastatic disease was defined as limited relapse (≤3 metastases), which remained amenable to local treatment. The PET/CT parameters SUVmax, SUVpeak, metabolic tumour volume (MTV) and tumour glycolytic volume (TGV) were derived using commercially available software (Hermes Medical Solutions, AB, Stockholm). The association of these parameters with patterns of subsequent metastatic relapse was tested using standard statistical techniques.

RESULTS The 24 patients were categorized as follows: 9 polymetastatic relapse, 4 oligometastatic relapse, 11 no relapse. All patients with an SUVmax > 13 had polymetastatic relapse within one year. There was a significant difference of SUVmax (7.47 vs 14.15, p=0.002) and TGV (79.5 vs 664.0, p=0.016) between those with polymetastatic relapse compared with oligometastatic or no relapse. The AUC for the ROC curve for SUVmax to predict polymetastatic compared with oligometastatic or no relapse at 12 months was 0.875 (Figure 1).

CONCLUSION

Baseline PET/CT can provide prognostic information for patients undergoing percutaneous ablation for solitary colorectal liver metastases, which may allow improved patient selection for local therapy. This may be because FDG-uptake reflects underlying differences in tumour biology.

CLINICAL RELEVANCE/APPLICATION

Selection for percutaneous ablation of colorectal liver metastases is based largely on technical, rather than biological, considerations. PET/CT can provide prognostic information, which may allow improved patient selection for local therapy.

RC401 Contemporary Imaging of Lung Cancer

Refresher/Informatics OI MR MI CT CH AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Tue, Dec 2 4:30 PM - 6:00 PM Location: N230AB Participants Moderator Jeremy J. Erasmus MD : Nothing to Disclose

Sub-Events RC401A Non-small Cell Lung Cancer Staging: Concepts and Controversies Ioannis Vlahos MRCP, FRCR (Presenter): Research Consultant, Siemens AG Research Consultant, General Electric Company LEARNING OBJECTIVES

1) Summarize the origins, basis and rationale of the current TNM classification of lung cancer. 2) Discuss the strengths and limitations of the current system and how to practically address these 3) Highlight areas where current radiology, oncological, surgical and pathological best practice and evolving knowledge in these area are progressing beyond the current staging system.

RC401B Contemporary Concepts in Small Cell Lung Cancer Fergus Vincent Gleeson MBBS (Presenter): Alliance Medical Ltd Consultant LEARNING OBJECTIVES

1) To learn the clinical manifestations, staging and prognostic factors of small cell lung cancer. 2) To become familiar with the role of PET-CT in the investigation and management of small cell lung cancer. 3) To review unusual presentations of small cell lung cancer and their investigation and treatment.

ABSTRACT Small cell lung cancer, SCLC, accounts for approximately 15% of all lung cancers, with its overall incidence decreasing, although it is increasing in women, with the male to female incidence ratio now 1:1. Small cell lung cancer has a more rapid doubling time than non-small cell lung cancer, with most patients presenting with hematogenous metastases, and only approximately one-third presenting with limited-stage disease confined to the chest. Small cell lung cancer uncommonly presents with a solitary pulmonary nodule, and the disease does not appear to have benefited from Lung Cancer Screening. There are multiple neurologic and endocrine paraneoplastic syndromes associated with small cell lung cancer, with marked improvement on treatment of the underlying tumour. Historically SCLC was staged according to the Veteran's Administration Lung Group's 2 stage classification of 1) extensive-stage disease or 2) limited-stage disease, and this classification used to guide therapy. More recently it has been recommended that SCLC is staged according to the International Association of the Study of Lung Cancer (IASLC) and the AJCC Cancer Staging Manual 7th edition, using the same staging system for NSCLC and SCLC. Whilst contrast enhanced CT scan of the chest and abdomen remain routine as the initial method for staging SCLC, FDG PET-CT now plays a more important role in staging and management. SCLC is a highly metabolic disease, and PET-CT both upstages and downstages disease, potentially altering management

RC401C PET Imaging of Lung Cancer: Beyond Standard Metabolic Assessment Eric Michael Rohren MD, PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Review advanced image processing and metabolic parameters in FDG-PET/CT. 2) Discuss non-FDG radiotracers and their potential applications in non-small cell lung cancer. 3) Illustrate the role of advanced PET/CT in case examples.

ABSTRACT

Assessment of non-small cell lung cancer with PET is typically performed using F-18 fluorodeoxyglucose (FDG). The uptake and retention of FDG by the tumor is taken to be a measure of metabolism, which in turn can provide useful information on staging, grading, and prognosis. Advances in the field of PET/CT imaging may provide additional information for the evaluation and care of patients with lung cancer. Advanced semi-quantitative analyses including total lesion glycolysis (TLG) and metabolic tumor volume (MTV) have been employed to capture additional information from FDG-PET/CT studies, which in some cases is additive to standard metabolic parameters such as SUVmax. New tracers are under development, with some nearing approval in the U.S. and elsewhere. These include tracers targeting proliferation, receptor expression, and protein catabolism, investigating molecular events and processes beyond glucose metabolism.

RC401D MRI: Advances in Nodule Characterization and Lung Cancer Staging Kyung Soo Lee MD, PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) To review most popular MRI techniques that are used in thoracic MR imaging. 2) To demonstrate how effective MR imaging is in nodule characterization and lung cancer staging, particularly focused on diffusion-weighted imaging (DWI) and diffusion-weighted whole-body imaging with background body signal suppression (DWIBS). suppression (DWIBS).

ABSTRACT

Diffusion-weighted MR imaging helps characterize lung nodule, and enables staging and prognosis prediction in lung cancer. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) is known to be specific in nodal staging and effective in whole body MR imaging. Both whole body MRI and PET-CT may be used in extra-thoracic lung cancer staging, but each modality has its own and different merits in lung cancer staging. Whole body MRI-PET may be the future oncologic imaging modality.

URL's

http://blog.naver.com/lks7629

RC401E CT Perfusion Imaging in Lung Cancer Friedrich D. Knollmann MD, PhD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) To identify suitable indications for the use of CT perfusion imaging in lung cancer. 2) To apply CT perfusion imaging to lung tumors. 3) To recognize important features of a valid CT perfusion imaging protocol. 4) To interpret the results of a CT perfusion study in lung tumors.

ABSTRACT CT perfusion (CTP) imaging has become a tenable proposition with the advent of multislice CT. Preliminary data have indicated a potential role in the assessment of treatment response in lung cancer, but the method is not widely used. In this course, the rationale for using CT perfusion imaging as a quantitative imaging biomarker in lung cancer is discussed. A review of CT protocols includes factors that have impeded a wider adoption of the method in the clinical sphere, such as the reproducibility of measurements, and validation efforts. Solutions to these problems, such as improved anatomic coverage with wider detectors and table motion, reduced radiation exposure with iterative reconstruction, advanced postprocessing with dual blood supply algorithms, motion registration and correction, and volumetric perfusion analysis are addressed. With these methods, tumor classification, assessment of tumor response, and prognostic testing are promising applications of CTP imaging.

RC401F Thoracic Oncologic Imaging: Treatment Effects and Complications Brett Wilson Carter MD (Presenter): Author, Reed Elsevier Consultant, St. Jude Medical, Inc LEARNING OBJECTIVES

1) Understand the role of imaging in the evaluation of patients who have been treated for thoracic malignancies. 2) Recognize the manifestations of radiation therapy in the chest and be able to differentiate expected changes from residual or recurrent disease. 3) Identify intrathoracic complications from radiation therapy, chemotherapy, and surgery.

ABSTRACT Imaging plays an important role in the evaluation of patients who have been treated with radiation therapy, chemotherapy, and/or surgery for intrathoracic malignancies such as lung cancer, esophageal cancer, malignant pleural mesothelioma, and thymoma. Following thoracic radiation therapy, radiation pneumonitis (1-6 months following therapy) and radiation fibrosis (6-12 months following therapy) are typically identified in the lungs. However, complications such as esophagitis, esophageal ulceration, and radiation-induced cardiovascular disease may develop. Patients treated with chemotherapy may develop pulmonary and cardiovascular complications such as drug toxicity, organizing pneumonia, thromboembolic disease, vasculitis, and cardiomyopathy. Knowledge of the spectrum of expected treatment-related changes, potential treatment complications and the appearance of tumor recurrence is critical in order to properly monitor patients, identify iatrogenic complications, and avoid misinterpretation.

SSK13 ISP: Molecular Imaging (Neurosciences)

Scientific Papers MR MI NR AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Wed, Dec 3 10:30 AM - 12:00 PM Location: S504CD

Participants Moderator Alexander Drzezga MD : Consultant, Siemens AG Consultant, Eli Lilly and Company Consultant, General Electric Company Consultant, Piramal Enterprises Limited Speaker, Siemens AG Speaker, Eli Lilly and Company Speaker, General Electric Company Speaker, Piramal Enterprises Limited Company Speaker, Piramal Enterprises Limited Moderator Satoshi Minoshima MD, PhD : License agreement, General Electric Company Research Grant, Koninklijke Philips Electronics NV Research Grant, Hitachi, Ltd Research Consultant, Hamamatsu Photonics KK Grant, Nihon Medi-Physics Co, Ltd Research Grant, Astellas Group Research Grant, Seattle Genetics, Inc

Sub-Events SSK13-01 Molecular Imaging Keynote Speaker: Imaging Microtubular Function and Pathology Satoshi Minoshima MD, PhD (Presenter): License agreement, General Electric Company Research Grant, Koninklijke Philips Electronics NV Research Grant, Hitachi, Ltd Research Consultant, Hamamatsu Photonics KK Grant, Nihon Medi-Physics Co, Ltd Research Grant, Astellas Group Research Grant, Seattle Genetics, Inc

SSK13-02 ME-MRI Demonstrating Improved Axonal Transport after Microtubule Stabilization in Alzheimer Transgenic Mice Donna Jean Cross PhD (Presenter): Research Grant, Hitachi, Ltd Research Grant, Astellas Group , Christopher Allen Potter MD : Nothing to Disclose , Nathalie M. Martin BA : Nothing to Disclose , Greg Garwin : Nothing to Disclose , Rodney Ho PhD : Nothing to Disclose , Satoshi Minoshima MD, PhD : License agreement, General Electric Company Research Grant, Koninklijke Philips Electronics NV Research Grant, Hitachi, Ltd Research Consultant, Hamamatsu Photonics KK Grant, Nihon Medi-Physics Co, Ltd Research Grant, Astellas Group Research Grant, Seattle Genetics, Inc PURPOSE Using MR imaging with manganese (ME-MRI) to assess bulk axonal transport rates in vivo, we reported previously decreased axonal transport in young mice transgenic (Tg) for Alzheimer's disease (AD). Microtubule stabilizing therapeutics have been shown to improve cognition and decrease pathology in AD Tg mice. For this current study, we hypothesized that intranasal administration of paclitaxel, a microtubule-stabilizing drug would improve transport rates in the olfactory tract of triple transgenic AD mice (3xTg-AD).

METHOD AND MATERIALS Mice, (3xTg-AD, n=15, age=75±10 days) were treated by intranasal lavage with either Paclitaxel (0.6 mg/kg; Hospira, Inc., Lake Forest, IL) or 0.9% saline vehicle in a volume of 5 µl per nostril. Mice received a total of 6 treatments at intervals of 14±0.2 days with post treatment imaging occurring at age=172±16 days. Scanning (14T Bruker MR: T1-weighted MDEFT, TR/TE: 5000ms/1.9ms, resolution 0.140 x 0.140 x 0.25mm3) pre and post treatment occurred at 100 min. and again from 280-350 min after administration of 5 µL of 1M MnCl2 intranasally. After imaging, mice were perfused and brains removed for histopathology. Images were coregistered, normalized and stereotactically aligned to a mouse brain atlas. Volumes of interest in the olfactory nucleus (ON) and lateral olfactory tract (OT) were used to measure average signal intensity change indicating Mn2+ transport. Uptake and rate of transport were estimated.

RESULTS

Lateral olfactory tract axonal transport was decreased 63% between pretreatment time (75 days of age) and post (approximately 6 mo. of age) in 3xTg-AD mice receiving saline treatment. This time period usually includes the onset and development of amyloid-related pathology and initial appearance of fibrillary tau in this Tg model. In comparison, mice receiving intranasal treatment with paclitaxel over the same period of time showed a 65% relative increase in OT transport rates. There were no significant differences in total Mn2+ uptake in the ON between groups, indicating delivery thru activity-dependent Ca2+ channels was not affected by treatment.

CONCLUSION

The ME-MRI results indicate that microtubule-stabilizing drugs may intervene the AD neuropathological cascade via normalization of axonal transport processes, which are critical to maintain homeostatic neuronal functions.

CLINICAL RELEVANCE/APPLICATION Microtuble-stabilizing drugs present an exciting new therapeutic option for Alzheimer's disease.

SSK13-03 Molecular MRI Detects Synergistic Combination of Glatiramer Acetate and Myeloperoxidase Inhibition in a Mouse Model of Multiple Sclerosis Anning Li MD (Presenter): Nothing to Disclose , Yue Wu : Nothing to Disclose , Cuihua Wang PhD : Nothing to Disclose , Benjamin Pulli MD : Nothing to Disclose , Gregory R. Wojtkiewicz MSc : Nothing to Disclose , Yoshiko Iwamoto : Nothing to Disclose , Muhammad Ali MBBS : Nothing to Disclose , JINGHUI LI PHD : Nothing to Disclose , Zhenwei Yao : Nothing to Disclose , John Chen MD, PhD : Research Grant, Pfizer Inc PURPOSE

Purpose: Glatiramer acetate (GA), a first-line drug for multiple sclerosis (MS), is thought to primarily increase Th2 anti-inflammatory lymphocytes while 4-animobenzoic acid hydrazide (ABAH) is an irreversible inhibitor for myeloperoxidase (MPO), a major product of pro-inflammatory myeloid cells. The aim of this study was to investigate whether the combination of these two agents could be more beneficial, and whether this benefit could be evaluated and tracked by molecular imaging targeting MPO.

METHOD AND MATERIALS Materials and Methods: 3 groups of experimental autoimmune encephalomyelitis (EAE) mice were given sub-optimal doses: ABAH 20mg/kg bid, GA 75μg qd, combination (ABAH 20mg/kg bid and GA 75μg qd) and saline as control. Mice were imaged when they first became symptomatic with bis-5HT-DTPA-Gd (MPO-Gd) MRI to assess MPO activity in vivo. Analysis of lesion number, lesion size and contrast-to-noise ratios (CNRs) was conducted. Histopathology was used to analyze the disease activity. Statistical analysis was performed using Student's t-test with P<0.05 as significant.

RESULTS Results: The combination group showed delayed disease onset, reduced disease severity (Fig. A) and significantly less disease burden (Fig. B) compared to the ABAH group (P<0.005) and GA group (P<0.05). The combined treatment also tended to improve survival (Fig. A). On imaging, the combination group showed fewer lesions (51.0±11.2 for combination vs. 100.8±11.9 for ABAH, P<0.01; vs. 87.3±14.6 for GA, P<0.05), smaller lesion size (23.9±4.5 for combination vs. 73.0±26.5 for ABAH, P<0.05; vs. 90.1±36.5 for GA, P<0.05) and lower image intensity (2.7±0.6 for combination vs. 6.8±1.3 for ABAH, P<0.01; vs. 4.6±0.7 for GA, P<0.05). Reduced disease severity was confirmed on histopathology, where inflammatory cells infiltration, MPO expression, and demyelination were attenuated (Fig. C).

CONCLUSION

Conclusion: Molecular MR imaging targeting MPO can track the beneficial effect of synergistic treatment effects of targeting lymphoid and myeloid inflammation, establishing MPO imaging as a potential imaging biomarker for MS.

CLINICAL RELEVANCE/APPLICATION

Clinical Relevance: Upon translation, MPO targeted MR imaging could be used to track MS treatment efficiency and guide treatment decisions.

SSK13-04 Targeted Gd Nanoparticle for T1-MR Molecular Imaging of Amyloid Plaques Eric Tanifum PhD (Presenter): Stockholder, Alzeca Biosciences LLC , Ketan B. Ghaghada PhD : Research Grant, Marval Biosciences Inc Consultant, Marval Biosciences Inc Shareholder, Marval Biosciences Inc , Zbigniew Starosolski PhD : Stockholder, Alzeca Biosciences, LLC , Ananth Annapragada PhD : Stockholder, Marval Pharma Ltd Stockholder, Alzeca Biosciences LLC Stockholder, Sensulin LLC Stockholder, Abbott Laboratories Stockholder, Johnson & Johnson PURPOSE

A hyper-relaxive Gd containing liposome targeted to amyloid plaques by a novel targeting ligand was fabricated. We tested (a) the ability of this particle to label amyloid plaques, and (b) detection of the labeling by T1-weighted MRI. If sufficiently sensitive and specific, such particles could be alternatives to PET based molecular imaging agents.

METHOD AND MATERIALS Liposomes targeted to amyloid plaques by a novel amyloid binding ligand, surface-coated with Gd-DOTA and containing ICG (10µM) for near-Infrared detection, were fabricated. They were injected into 9-month old Tg2576 mice via the tail vein at a dose of 8µL/gram body weight. Imaging pre-contrast and at daily intervals up to 5 days post-contrast was conducted using a 1T permanent magnet based system, and a T1 weighted spin-echo sequence with TE=30ms, TR=700ms, FA=90°, NEX=4. The animals were sacrificed, brains perfused with saline, fixed with formaldehyde, and immersed in 10% sucrose. 20µ frozen alternating sections were stained with 4G8 antibody and visualized with a Cy3 labeled secondary antibody to confirm amyloid burden. The other alternate sections were visualized unstained in both in bright field, and for ICG.

RESULTS Amyloid positive animals (n=6) treated with the targeted liposomes showed clear T1 signal in the hippocampus and cerebral cortex, while both amyloid positive animals treated with a control untargeted formulation (n=6), and amyloid negative animals treated with the targeted formulation (n=6) showed no such signal. Histologically, the presence of amyloid plaques only in the brains of the positive animals was confirmed, as was the presence of the fluorescent ligand and the ICG only in the positive animals treated with the targeted formulation.

CONCLUSION The MRI data are clearly consistent with avid labeling of amyloid plaques in this animal model by the targeted liposomes, with sufficient sensitivity for T1 weighted imaging using 1T field strength. The histological data confirmed the presence of amyloid plaques in the positive animals as well as the presence of targeted particles in the brains of the amyloid positive animals treated with them.

CLINICAL RELEVANCE/APPLICATION

The high sensitivity and specificity suggest this agent could be highly successful in imaging amyloid plaques, and could be worthy of development an alternative to currently available PET ligands.

SSK13-05 Molecular MRI Detection of Traumatic Brain Injury (TBI) with Amide Proton Transfer (APT) Imaging Hong Zhang MD (Presenter): Nothing to Disclose , Wen zhu Wang : Nothing to Disclose , Bo Ma : Nothing to Disclose , Yun Peng MD : Nothing to Disclose , Jian Wang : Nothing to Disclose , Jinyuan Zhou PhD : Nothing to Disclose PURPOSE In the TBI, the initial impact includes the primary injury and secondary injury cascades, such as ischemia, progressive neurodegeneration, persistent inflammation, glial hypertrophy and proliferation, and cerebrovascular dysfunctions. APT imaging is a novel molecular MRI method that can non-invasively detect endogenous mobile protein and tissue pH changes. We explored the capabilities of APT imaging for detecting the TBI in rat models.

METHOD AND MATERIALS Six adult male SD rats had craniotomy plus controlled cortical impact (CCI) surgery (3-mm impactor tip, velocity of 5m/sec, deformation depth of 5 mm, and impact duration of 65 msec) under isoflurane anesthesia. MRI data was acquired at 4.7T, using T2w, T2*w, T1w, T2, T1, isotropic ADC, CBF, and APT-weighted (APTw; RF saturation power/time 1.3 μT/4 sec) MRI. APTw images were quantified using the magnetization transfer-ratio asymmetry at 3.5 ppm from water. MRI was performed 1 and 6 hours, as well as 1, 2 and 3 days after TBI.

RESULTS All APTw images show an 'ischemia-like' pattern of hypointensity, unique from all other used MRI sequence, in some areas of the lesion. Average APTw signal intensities decreased significantly and globally at 1 hr (compared to contralateral normal brain tissue), with 84%, 63% and 62% reductions in a contused cortical region, ipsilateral hippocampus and thalamus. There were some areas of intermediate to slightly hyperintense APT signals in the lesion, consistent with the hemorrhage (with abundant mobile proteins), as shown by T2*w and pathology. The low APT-pH MRI signal was gradually recovered after the initial drop. At day 3 after injury, the TBI lesion became heterogeneous with areas of high and low APTw signal intensities. Notably, the APTw signal intensity of the perilesion cortex dramatically increased (3.3% ± 1.5% at 3d vs. -3.2% ± 1.6% at 1 h), due to the secondary inflammatory response, as confirmed by pathology.

CONCLUSION

This study for the first time demonstrates that APT-MRI can reveal many key TBI features in vivo, such as ischemia, hemorrhage, and inflammatory response.

CLINICAL RELEVANCE/APPLICATION

The APT-MRI signal is a unique, sensitive biomarker for identifying and assessing the TBI in the clinic, which should have considerable influence on the patient care.

SSK13-06 Metabolic Coherence Mapping of the Brain to Elucidate Regional Neuronal Activity and Functional Integration: Multivariate Correlational Analysis Using Dynamic FDG PET Marcella Cline BS (Presenter): Nothing to Disclose , Satoshi Minoshima MD, PhD : License agreement, General Electric Company Research Grant, Koninklijke Philips Electronics NV Research Grant, Hitachi, Ltd Research Consultant, Hamamatsu Photonics KK Grant, Nihon Medi-Physics Co, Ltd Research Grant, Astellas Group Research Grant, Seattle Genetics, Inc , Donna Jean Cross PhD : Research Grant, Hitachi, Ltd Research Grant, Astellas Group , Alexander Drzezga MD : Consultant, Siemens AG Consultant, Eli Lilly and Company Consultant, General Electric Company Consultant, Piramal Enterprises Limited Speaker, Siemens AG Speaker, Eli Lilly and Company Speaker, General Electric Company Speaker, Piramal Enterprises Limited , Daniel S. Hippe MS : Research Grant, Koninklijke Philips NV Research Grant, General Electric Company , Barbara L. Lewellen BS : Nothing to Disclose , Greg Garwin : Nothing to Disclose PURPOSE The functional integrity of neural activity via circuitries/pathways is thought to be reflected on regional intercorrelation of neuronal activity ('functional connectivity'). This study investigates the feasibility of such parametric mapping using individual FDG-PET imaging and compared to standard static images.

METHOD AND MATERIALS

Ten non-human primates underwent dynamic brain PET imaging under sevoflurane anesthesia. Following a slow-bolus injection of 3 mCi [F-18]FDG, 120 30-second dynamic frames were obtained over 60 min. Following frame-to-frame image coregistration, stereotactic transformation, and global normalization, voxel-wise principal component analysis (PCA) with matrix transposition was applied to the individual data sets, followed by Varimax rotation of initial components. Individual quantitative Metabolic Coherence (MC) maps were created by averaging absolute component loadings and compared to conventional static FDG maps.

RESULTS

In all subjects, the first 2 components represented large variances (76% +/-11 SD to total variance) resulting from general blood flow and tissue FDG uptake that were eliminated by exclusion of the initial vascular phase in the dynamic data. Individual MC maps elucidated cerebral structures involved in the default mode network with high composite correlation coefficients: posterior cingulate cortex (0.070+/-0.006); frontal (0.070+/-0.005), parietal (0.069+/-0.006), and temporal (0.069+/-0.005) association cortices. MC values were modest in the striatum (0.059+/-0.007) and low in the visual cortex (0.039+/-0.005, presumably due to anesthesia) and cerebellum (0.035+/-0.007). In contrast, conventional static FDG maps from the same subjects showed high metabolic values (normalized to global activity 100) in the striatum (148+/-9.4); posterior cingulate cortex (136+/-6.5); parietal (134+/-6.9) and frontal (124+/-7.7) association cortices.

CONCLUSION

While static FDG maps represent regional neuronal activity, MC maps potentially provide unique supplementary While static FDG maps represent regional neuronal activity, MC maps potentially provide unique supplementary information concerning regional functional integration via intercorrelation across regions within the brain. Further validation and optimization are underway.

CLINICAL RELEVANCE/APPLICATION

New parametric analysis of dynamic FDG-PET depicts regional neuronal activity and functional integrity that can supplement conventional static image interpretation and shed light on disease processes.

SSK13-07 Amyotrophic Lateral Sclerosis: Impact of Disease Progression on Intraspinal Stem Cell Survival Amit Srivastava : Nothing to Disclose , Sarah Gross : Nothing to Disclose , Camille Bulte : Nothing to Disclose , Akshata Almad : Nothing to Disclose , Nicholas Maragakis : Nothing to Disclose , Jeff W.M. Bulte PhD (Presenter): Research Grant, Koninklijke Philips NV Founder and co-owner, SenCEST, LLC PURPOSE The first Phase I clinical trials have shown that neural stem cell (NSC) therapy represents a possible new treatment for Lou Gehrig's disease (ALS), a motor neuron disease for which there is no cure. Monitoring the the survival of transplanted cells is imperative for determining the therapeutic success. The purpose here was to monitor graft survival as related to the progression of motor deficits.

METHOD AND MATERIALS

Allogeneic luciferase-transfected NSCs were transplanted bilaterally (100,000 cells) into the cervical spinal cord (C5) of presymptomatic SOD1(G93A) transgenic ALS mice (n=9) and wild type littermates (n=5) via laminectomy. Mice were immunosuppressed by using FK506/rapamycin (1 mg/kg, i.p.) daily. Bioluminescence imaging (BLI) and computed tomography (CT) were performed for several weeks post-transplantation using a dual-mode Perkin Elmer Spectrum/CT. Rota rod test was performed to determine motor deficits. Disease onset was defined by decline in motor skills and weight loss.

RESULTS BLI showed no excessive proliferation of transplanted cells (Fig. 1A). The first sign of disease onset was observed in 84 days old ALS mice. Motor skills continued to decline further, Compared to day 1, a 60% decline in BLI signal was observed in ALS mice after four weeks of transplantation (at the time of disease Anchoronset) (p<0.05) (Fig. 1B). The decrease of cell survival preceded the decline in motor skills and, interestingly, showed the same overall time course pattern. There was a complete loss of BLI signal at the end point. In contrast, only 10% decline in the BLI signal was observed in wild type littermates after four weeks of transplantation. Anti-Iba1 (red) and anti-luciferase (green) staining showed the presence of activated microglia around engrafted cells in the spinal cord of symptomatic ALS mice (Fig. 1C).

CONCLUSION

The disease onset and progression adversely affect the survival of engrafted NSCs in ALS. This poor survival is likely a result of the pathological microenvironment in the spinal cord of ALS mice.

CLINICAL RELEVANCE/APPLICATION

The hostile microenvironment of the spinal cord in ALS represents a significant barrier for successful clinical therapy.

SSK13-08 Increased Uptake of 2-[18F]fluoroacetate at Early Phase of Cerebral Ischemia Ryuichi Nishii MD, PhD (Presenter): Nothing to Disclose , Hiroshi Mizuma PhD : Nothing to Disclose , Shinya Kagawa : Nothing to Disclose , Tatsuya Higashi MD : Nothing to Disclose , Hiroshi Yamauchi MD, PhD : Nothing to Disclose , Youichi Mizutani : Nothing to Disclose , Shigeki Nagamachi MD, PhD : Nothing to Disclose , Hirotaka Onoe PhD : Nothing to Disclose PURPOSE 2-[18F]Fluoroacetate (FACE) has been considered as a PET probe for evaluating glial metabolism (Marik et al., JNM, 2009), though little is known about its detailed functions in cerebral ischemia. We here examined changes in brain uptake of [18F]FACE by PET during cerebral ischemia, in combination with immunohistochemistry study for confirming glial cell activation associated with neuroinflammation.

METHOD AND MATERIALS Rats were occluded in the right middle cerebral artery for 60 min, and were reperfused, subsequently (tMCAO). [18F]FACE-PET scan for 60 min under isoflurane anesthesia was conducted at 2 hr (early phase) and 7th day (later phase) after reperfusion. Glial activation was assessed by both [11C]PK11195-PET imaging for translocator protein (TSPO) and immunohistochemical staining with anti-CD11b and anti-GFAP antibodies for activated microglia and reactive astrocyte, respectively. Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining after PET imaging.

RESULTS [18F]FACE uptake in the lesion side at 2 hr after reperfusion was significantly high compared with that in the contralateral side (p CONCLUSION CONCLUSION These finding indicate that [18F]FACE-PET imaging could visualize the preinfarct area without any glial activation associated with neuroinflammation.

CLINICAL RELEVANCE/APPLICATION [18F]FACE uptake at early stage of cerebral ischemia might be tightly associated with emergent metabolic shift coupled with neural dysfunction.

SSK13-09 18F-FDG-PET, Pulsed Arterial Spin Labeling MRI and Structural MRI in Mild Cognitive Impairment and Alzheimer’s Disease: A Simultaneous PET/MRI Study Peter Bohn : Nothing to Disclose , Isabelle Riederer : Nothing to Disclose , Christine Preibisch : Nothing to Disclose , Panos Alexopoulos : Nothing to Disclose , Markus Schwaiger MD : Research Grant, Siemens AG , Stefan Forster MD (Presenter): Research Consultant, Bayer AG Speakers Bureau, General Electric Company Research Consultant, Merck KGaA Research Consultant, Piramal Enterprises Limited PURPOSE Previous studies showed specific abnormality patterns as well as high pattern accordance between cortical PET hypometabolism-, ASL MRI hypoperfusion- and T1w MRI atrophy in Alzheimer�s disease (AD) and mild cognitive impairment (MCI). Whereas former studies were conducted on separate scanners at different time points we aimed to compare these three methods directly utilizing simultaneous PET/MRI in patients with MCI, patients with AD and healthy control subjects.

METHOD AND MATERIALS 19 AD- and 14 MCI patients and 11 matched healthy elderly controls (HC) were included in this prospective study. Patients and subjects were examined on a Siemens mMR Biograph integrated PET/MRI scanner, using a simultaneous acquisition protocol (pulsed arterial spin labeling (PASL) MRI, T1w MPRAGE MRI and 18F-FDG-PET). Matlab, SPM8/VBM8 based preprocessing was executed and voxelwise statistical comparisons between AD, MCI and HC were carried out (t-tests; p>0.001; kE=20).

RESULTS Relative to HC distinct hypometabolism and hypoperfusion occurred in bilateral posterior cingulate- and bilateral superior parietal cortex for AD and left superior parietal cortex for MCI, while mild atrophy in the latter regions occurred only for AD. In MCI and AD most distinct atrophy without co-localization of hypometabolism and hypoperfusion occurred in bilateral medial- and inferior temporal cortical regions.

CONCLUSION Applying simultaneous PET/MRI in MCI and AD, patterns of cortical hypoperfusion and hypometabolism showed high correspondence and did mainly not result from effects of regional cortical atrophy, which occurred most distinctively in medial- and inferior temporal regions. We suggest that in a group-based evaluation PASL MRI delivers comparable results to 18F-FDG-PET in the diagnosis of neurodegenerative MCI/AD, having the advantages of non-invasiveness and non-radiation exposure. PASL MRI might be a future alternative to 18F-FDG-PET in the PET/MRI diagnostic work-up of patients with neurodegenerative dementia, i.e. in combination with amyloid-PET. However, PASL MRI needs further evaluation on a patient basis and regarding its quantitative features.

CLINICAL RELEVANCE/APPLICATION Our abstract has high clinical relevance, as non-invasive and radiation exposure free neuroimaging methods such as arterial spin labeling MRI have high potential to be translated in the diagnostic work-up of patients with neurodegenerative dementia and other diseases.

MIS-WEA Molecular Imaging Wednesday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Wed, Dec 3 12:15 PM - 12:45 PM Location: S503AB

Participants Moderator Jan Grimm MD, PhD : Research Consultant, Progenics Pharmaceuticals, Inc Shareholder, Nortis, Inc Moderator Donna Jean Cross PhD : Research Grant, Hitachi, Ltd Research Grant, Astellas Group

Sub-Events MIS139 A Comparison between FDG PET/CT, CT and MRI in Detection of Spinal Metastases and Its Impact on Clinical Management [ MI Scavenger Hunt! ] (Station #7) Ahmed Wafaie (Presenter): Nothing to Disclose , Nevien Ezzat El-Liethy : Nothing to Disclose , Hassan Kassem MD : Nothing to Disclose , Magdy Kotb : Nothing to Disclose PURPOSE To compare the diagnostic value of combined F18-FDG PET/CT, CT and MRI in detection of spinal metastatic lesions and itsimpact on clinical management

METHOD AND MATERIALS

22 patients with biopsy-proven malignancy were enrolled. All underwent spinal MRI and whole body F-18-FDG PET/CT examinations using standard techniques. The diagnostic capabilities of the imaging modalities were compared in the same spinal field of view. FDG PET/CT and MRI findings were compared with the results of biopsy or clinical/ radiological follow up for at least 12 months as reference standards

RESULTS A total of 214 vertebral lesions were detected in 22 cancer patients based on combined clinical/ radiological follow up, these lesions were divided into: 129 metastatic and 85 benign lesions. Moreover these 22 patients were divided into: 12 with spinal metastases and 10 free from metastases. Both lesionandpatient-based data analysis showed significant higher diagnostic accuracy for combined F18-FDG PET/CT (98.5% and 95.4%) compared to MRI (86% and 68%) and CT (79.5% and 54.5%) respectively. The significant difference between F18 FDG PET/CT and morphological techniques were more obvious on specificity indices rather than sensitivity indices in both lesion and patient based analysis. On lesion-based analysis, the sensitivity, specificity,NPV and PPV for F18 FDG PET/CT were 99%, 98%, 98% and 99%, For MRI were 88.4%, 82.3%,88.4%and 82.3%, and for CT were 83.7%, 73%,82.4 and 74.5% respectively. On patient-based analysis the sensitivity and specificity for F18 FDG PET/CT were 100% and 90% compared to 75% and60% in MRI and 66.6 % and40% in CT. The relative superiority of the F18 FDG based technique compared to the morphological techniques in respect to sensitivity and specificity provided significant changes in patient management in 27.2 % and 41%compared to MRI and CT respectively.

CONCLUSION Combined F18 FDG PET/CT scan showed the highest sensitivity, specificity and accuracy followed by MRI and lastly CT in detection of spinal metastases . Consequently18F-FDG PET/CT has a better impact on clinical management compared to MRI and CT

CLINICAL RELEVANCE/APPLICATION

F18 FDG PET/CT showed much higher sensitivity, specificity and accuracy compared to MRI and CT in detection of spinal metastatic lesions and hence had a high impact on clinical management. therefore, a whole body FDG PET/CT is enough for staging/ re-staging and MRI is not required unless clinically suspected neural compromise is there

MIS140 pH-Sensitive Nanomicelles for Controlled and Efficient Drug Delivery to Colorectal Cancer Cells (Station #8) Yanji Luo (Presenter): Nothing to Disclose , Shiting Feng MD : Nothing to Disclose , Ziping Li MD, PhD : Nothing to Disclose PURPOSE

To develop a nano-micelle for anti-tumor drug delivery and intracellular drug release triggered by pH.

METHOD AND MATERIALS

The pH sensitive copolymer PEG-P(Asp-DIP)-P(Lys-Ca) (PEALCa) was designed in our study. In order to demonstrate the target and therapeutic potential of the vesicle, cell culture experiments of the PTX-SPIO-loaded vesicles against human colorectal cancer LoVo cells were conducted. Besides, as a MRI-visible drug delivery system, the intracellular drug release of the vesicles in vivo was studied by MRI to validate the efficiency. Our study attempts to explore the transferring efficiency of PTX-PEALCa into tumoral cells and anti-cancer improvement of PTX-PEALCa compared to conventional anti-cancer drugs.

RESULTS Drug release study revealed that PTX in the vesicles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa was effectively internalized by human colon carcinoma cell line (LoVo cells), and PTX could be embedded inside lysosomal compartments. Moreover, the colorectal cancer delivery effect was verified in vivo with magnetic resonance imaging (MRI) and histology analysis. Consequently effective suppression of cancer cell growth was detected.

CONCLUSION

These results indicated that the PTX-SPION-loaded pH-sensitive vesicles were a promising MRI-visible drug release system for colorectal cancer therapy.

CLINICAL RELEVANCE/APPLICATION The pH-triggered drug release was found to efficiently amplify the intracellular drug concentration which determined the anticancer outcome. The drug-delivery effect in vivo was visible by MRI technology. The results of this study revealed the great potential of PTX-SPIO-PEALCa vesicles as a multifunctional nanomedicine for tumor therapy. MIS141 A Prototype Opto-nuclear Probe for Combined Radio- and Fluorescence-guided Sentinel Node Biopsy (Station #9) Nynke S. Van Den Berg MSc (Presenter): Nothing to Disclose , Gijs Kleinjan MD : Nothing to Disclose , Thijs Engelen BSC : Nothing to Disclose , Herve Simon : Employee, Eurorad SA , Renato Valdes Olmos : Nothing to Disclose , Fijs Willon Bernard van Leeuwen PhD : Nothing to Disclose PURPOSE The recent introduction of hybrid tracer(s) such as indocyanine green (ICG)-99mTc-nanocolloid for sentinel node (SN) biopsy has led to the introduction of a fluorescence camera into the operating room, next to the already present gamma probe. Implementation of such new techniques might interfere with clinical logistics and can be associated with a learning curve. The prototype opto-nuclear probe (Eurorad) is a modified "conventional" gamma probe in which optical fibers are built in. It allows for combined intraoperative acoustic gamma tracing and fluorescence tracing of the near-infrared dye ICG via an acoustic output. This study evaluated the sensitivity of this prototype opto-nuclear probe for sentinel node (SN) biopsy.

METHOD AND MATERIALS SNs of 31 patients scheduled for SN biopsy in the head and neck- or urogenital area were evaluated. After ICG-99mTc-nanocolloid injection lymphoscintigraphy and SPECT/CT imaging was performed to determine the number and location of the SN(s). During the operation, SNs were excised using the combination of gamma tracing and fluorescence imaging (PhotoDynamic Eye (PDE), Hamamatsu Photonics). Post-excision, all excised nodes were evaluated with the prototype opto-nuclear probe. Obtained results with the prototype opto-nuclear probe were compared to the conventional approach.

RESULTS Ex vivo 112 nodes were evaluated: 98 SNs (both radioactive and fluorescent) and 14 non-SNs (neither radioactive nor fluorescent). The prototype opto-nuclear probe accurately predicted the presence/absence of radioactivity in 100.0% of the excised nodes. Compared to fluorescence imaging using the PDE, initially 66.1% of the nodes was correctly predicted via fluorescence tracing with the prototype opto-nuclear probe. This increased to 95.5% after improving the sensitivity of the prototype opto-nuclear probe.

CONCLUSION Ex vivo, the prototype opto-nuclear probe allows for both acoustic gamma- and fluorescence tracing of the signatures of the hybrid tracer. Further in vivo evaluation is required to determine its value for fluorescence detection during the operation.

CLINICAL RELEVANCE/APPLICATION The introduction of a hybrid imaging modality that is based on the conventional standard might improve its adaptation in the clinical workflow, and as such lead to a better integration of hybrid tracers.

MIS-WEB Molecular Imaging Wednesday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Wed, Dec 3 12:45 PM - 1:15 PM Location: S503AB

Sub-Events MIS144 Tracking of Tumor-specific T Cells by MR Imaging and Multispectral Optoacoustic Tomography (MSOT) (Station #7) Melanie Kimm (Presenter): Nothing to Disclose , Reinhard Meier MD, PhD : Nothing to Disclose , Ernst J. Rummeny MD : Nothing to Disclose , Vasilis Ntziachristos PhD : Stockholder, iThera Medical GmbH , Stratis Tzoumas : Nothing to Disclose , Marcus Settles PhD : Nothing to Disclose PURPOSE To track tumor-specific T cells to tumors and visualize their biodistribution with MRI and multispectral optoacoustic tomography (MSOT).

METHOD AND MATERIALS CD8+ T cells expressing a T cell receptor specific for an ovalbumin peptide were used for the adoptive transfer. Tumors were introduced by murine lymphoma cell lines. Before transfer, T cells were labeled with iron nanoparticles or near infrared dyes. Labeling efficiencies were evaluated with phantom studies, IHC and IF/darkfield microscopy, respectively. Cell viability and functionality was analysed by flow cytometry, MTT and ELISA studies. Monitoring was performed with a MRI system (3T, Philips, Germany) and MSOT (iTheraMedical, Germany) at day 3 after adoptive transfer.

RESULTS Cell viability and survival is depending on the concentration and incubation conditions (e.g. time, temperature) of the contrast agent. By optimizing the protocols, we reach over 80% cell survival with no difference in functionality compared to unlabeled control T cells. Phantom studies revealed the visualisation of as little as 100.000 cells by MRI and 1.000 cells by MSOT, respectively. In vivo analysis showed that transfered labeled T cells accumulate at the tumor site and in peripheral lymphoid organs (spleen, lymph nodes). cells accumulate at the tumor site and in peripheral lymphoid organs (spleen, lymph nodes).

CONCLUSION Tumor-reactive T cells can be intracellularly labeled with iron nanoparticles and near infrared dyes at concentrations that do not harm the cells. At these conditions cells can be identified by using MRI and MSOT. Not only the tumor homing can be followed but also the biodistribution of the cells can be monitored.

CLINICAL RELEVANCE/APPLICATION Tracking of cytotoxic T lymphocytes with non-invasive imaging techniques such as MRI and MSOT is feasible and may lead to a better understanding of the biodistribution of transfered T cells for a rapid identification of responding patients shortly after the adoptive transfer.

MIS145 Correlation of Perfusion MRI and 18F-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation (Station #8) Ralf Eschbach (Presenter): Nothing to Disclose , Wolfgang Fendler : Nothing to Disclose , Marcus Hacker MD : Nothing to Disclose , Philipp Maximilian Kazmierczak MD : Nothing to Disclose , Heidrun Hirner PhD : Nothing to Disclose , Lukas Havla : Nothing to Disclose , Jessica Schuster : Nothing to Disclose , Matthias Moser : Nothing to Disclose , Konstantin Nikolaou MD : Speakers Bureau, Siemens AG Speakers Bureau, Bracco Group Speakers Bureau, Bayer AG , Maximilian F. Reiser MD : Nothing to Disclose , Clemens Christian Joachim Cyran MD : Research Grant, Bayer AG Research Grant, Novartis AG Speakers Bureau, Bayer AG PURPOSE To investigate a multimodal, multiparametric perfusion MRI / 18F-FDG-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation.

METHOD AND MATERIALS Human colorectal adenocarcinoma xenografts (HT-29) were implanted subcutaneously in n=17 (n=10 therapy group; n=7 control group) female athymic nude rats (Hsd:RH-Foxn1rnu). The animals were imaged at baseline and after a one-week daily treatment with regorafenib (10 mg/kg bodyweight) using a multimodal, multiparametric perfusion MRI / 18F-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min), plasma volume (PV, %) and extraction flow (EF, mL/100 mL/min) were calculated. In 18F-fluoro-deoxyglucose-(18F-FDG)-PET, tumor-to-background-ratio (TTB) was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor angiogenesis (CD-31) and cell proliferation (Ki-67).

RESULTS Regorafenib significantly (p CONCLUSION A multimodal, multiparametric perfusion MRI / PET imaging protocol allowed for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas with significant correlations between perfusion MRI parameters and 18F-FDG-PET, as validated by immunohistochemistry.

CLINICAL RELEVANCE/APPLICATION There is a high demand for non-invasive functional imaging biomarkers for an early and reliable monitoring of the effects of new anti-angiogenic agents in oncology.

MIS146 Amide Proton Transfer (APT) Imaging for Characterization of Thoracic Nodule and Mass: Preliminary Experience as a New MR-Based Molecular Imaging Method in Thoracic Oncology [ MI Scavenger Hunt! ] (Station #9) Yoshiharu Ohno MD, PhD (Presenter): Research Grant, Toshiba Corporation Research Grant, Koninklijke Philips NV Research Grant, Bayer AG Research Grant, DAIICHI SANKYO Group Research Grant, Eisai Co, Ltd Research Grant, Terumo Corporation Research Grant, Fuji Yakuhin Co, Ltd Research Grant, FUJIFILM Holdings Corporation Research Grant, Guerbet SA , Masao Yui : Employee, Toshiba Corporation , Cheng Ouyang : Employee, Toshiba Corporation , Mitsue Miyazaki PhD : Employee, Toshiba Corporation , Mizuho Nishio MD, PhD : Research Grant, Toshiba Corporation , Hisanobu Koyama MD, PhD : Nothing to Disclose , Shinichiro Seki : Nothing to Disclose , Takeshi Yoshikawa MD : Research Grant, Toshiba Corporation , Sumiaki Matsumoto MD, PhD : Research Grant, Toshiba Corporation , Yu Ueda PhD : Nothing to Disclose , Katsusuke Kyotani RT : Nothing to Disclose , Kazuhiro Kubo RT : Nothing to Disclose , Kazuro Sugimura MD, PhD : Research Grant, Toshiba Corporation Research Grant, Koninklijke Philips NV Research Grant, Bayer AG Research Grant, Eisai Co, Ltd Research Grant, DAIICHI SANKYO Group PURPOSE

Amide proton transfer (APT) imaging is one of the chemical exchange saturation transfer (CEST) imaging methods, and demonstrates the exchange between protons of free tissue water and the protons of amide groups (-NH) of endogenous proteins and peptides. In addition, APT is considered as one of the MR-based molecular imaging methods, and suggested as having the capability for tumor grade evaluation and/ or biological behavior assessment. The purpose of this study was to determine the capability of APT imaging for characterization of thoracic nodule and mass, and determine a potential as a new MR-based molecular imaging method in thoracic oncology.

METHOD AND MATERIALS Seventeen consecutive patients (13 men and 4 women; mean age 68 years) underwent APT imaging at a 3.0T MR system and pathological and/or follow-up examinations. According to final diagnoses, all thoracic lesions were divided as follows: malignancy (6 adenocarcinomas, 4 squamous cell carcinomas and 2 lymphomas) and benign (3 organizing pneumonias, 1 leiomyoma, 1 simple thymoma) groups. To obtain APT imaging data in each subject, respiratory-synchronized fast advanced spin-echo images were conducted following a series of magnetization transfer (MT) pulses. Then, magnetization transfer ratio asymmetry (MTRasym) was calculated from z-spectra in each pixel, and MTRasym map was computationally generated. To evaluate the capability for characterization of thoracic lesion, MTRasyms assessed by ROI measurements were compared between benign and malignant groups, between lung cancers and lymphomas, and between adenocarcinomas and squamous cell carcinomas by Student's t-test.

RESULTS

MTRasym of malignant group (3.3±2.7 %) was significantly higher than that of benign group (0.3±0.3 %, p=0.03). MTR asym of lymphoma (8.0±3.9 %) showed significantly higher than that of lung cancer (2.3±1.2 %, p=0.001). MTR asym of adenocarcinoma (2.9±1.2 %) was significantly higher than that of squamous cell carcinoma (1.4±0.2 %, p=0.04).

CONCLUSION

APT imaging has a potential for non-invasive characterization of thoracic nodule and mass, and play as a new MR-based molecular imaging method in thoracic oncology.

CLINICAL RELEVANCE/APPLICATION

APT imaging has a potential for non-invasive characterization of thoracic nodule and mass, and play as a new MR-based molecular imaging method in thoracic oncology.

MIS147 Integrated [11C]-Methionin PET/MRI for Diagnosing Brain Tumors in Accordance with WHO Grading (Station #10) Lale Umutlu MD (Presenter): Consultant, Bayer AG , Thorsten D. Poeppel : Nothing to Disclose , Cornelius Deuschl : Nothing to Disclose , Oliver Mueller : Nothing to Disclose , Christoph Poettgen : Nothing to Disclose , Philipp Heusch MD : Nothing to Disclose , Thomas C. Lauenstein MD : Nothing to Disclose , Michael Forsting MD : Nothing to Disclose , Marc U. Schlamann : Nothing to Disclose PURPOSE

To investigate the diagnostic ability of simultaneous [11C]-Methionin PET/MRI for assessment of tumor delineation and potential differences in tracer uptake values of brain tumors in accordance with the WHO Grading System.

METHOD AND MATERIALS

A total of 35 patients with primary or recurrence of brain tumors were enrolled in this trial. Brain tumors were assigned into subgroups according to the WHO Classification and comprised 13 low-grade tumors, 5 grade 3 tumors and 17 high-grade tumors. Simultaneous [11C]-Methionin PET/MRI examinations were performed on a Biograph mMR (3 Tesla, Siemens) applying 0.05mmol kg/bw Gadoteric acid (Dotarem, Guerbet). The scan protocol comprised: 1) FLAIR, 2) DWI, 3) T1 TSE, 4) SWI and 5) MPRAGE post contrast. The datasets were read separately by two radiologists in regard of (1) tumor delineation, (2) overall image quality and (3) artifact impairment utilizing a five-point scale (5= excellent; 1 = non-diagnostic). Maximum standardized uptake values (SUVmax) were measured for all detected tumor lesions. All available data (histology, prior examinations, PET/MRI, follow-up examinations) served as standard of reference. Mean values were compared using Wilcoxon rank sum test.

RESULTS All PET/MRI examinations were completed successfully and provided high-ratings in overall image quality (4.8) and minor artifact impairment (4.7). Evaluation of SUVmax showed increasing tracer uptake values with increasing malignancy, encompassing mean SUVmax of 2.6 for low-grade tumors, mean SUVmax of 3.2 for grade 3 tumors and mean SUVmax of 4.1 for high grade tumors. Statistical significant increase of SUVmax was detected between low and high grade tumors (p<0.05).

CONCLUSION

Simultaneous PET/MRI offers high quality assessment of morphologic and metabolic features of brain tumors, providing additional information for prognostic stratification in accordance with WHO grading, while preserving comparable examination times to standardized clinical MR examinations due to simultaneous data acquisition.

CLINICAL RELEVANCE/APPLICATION

Simultaneous PET/MRI bears the potential to offer valuable additional information for differential diagnosis and prognostic stratification of brain tumors.

MIS148 Radiosynthesis and Biological Evaluation of a Novel 18F-labeled α,α-disubstituted Amino Acid for Brain Tumor Imaging [ MI Scavenger Hunt! ] (Station #11) AHLEM BOUHLEL (Presenter): Nothing to Disclose , Dong Zhou : Nothing to Disclose , AIXIAO LI : Nothing to Disclose , Liya Yuan MD : Nothing to Disclose , Keith M. Rich MD : Nothing to Disclose , Jonathan Edward McConathy MD, PhD : Speakers Bureau, Eli Lilly and Company Research Consultant, Eli Lilly and Company Research Consultant, General Electric Company Research Consultant, Blue Earth Diagnostics Ltd Research Consultant, Siemens AG PURPOSE

Radiolabeled amino acids (AAs) that cross the blood-brain barrier (BBB) through system L transport and are also concentrated and retained in tumors through system A transport may have improved imaging properties over existing system L tracers for brain tumors such as [18F]FDOPA and [18F]FET. The objective of this project is to develop 18F-labeled analogues of these AAs with longer alkyl chain with the optimal balance of transport by system A and system L.

METHOD AND MATERIALS

Efficient organic and radiosynthetic routes were developed to obtain the target compound, (S)-2-amino-5-[18F]fluoro-2-methylpentanoic acid ((S)-[18F]FAMPe). The 18F incorporation was successfully performed in t-amyl alcohol to afford intermediate in 79 % yield, determined by radio-TLC and HPLC. Then, after a high yield purification by a C-18 HPLC column, a quantitatively deprotection and a Dionex OnGuard II A cartridge treatment, ((S)-[18F]FAMPe was obtained in 24% decay corrected yield and over 99% radiochemical purity in a form suitable for animal studies. Biodistribution studies were conducted in male BALB/c mice with subcutaneous DBT gliomas at 5, 30 and 60 min after injection (n= 5).

RESULTS

The new tracer demonstrate high uptake in DBT tumors (7.37 %ID/g at 30 min and 9.88 %ID/g at 60 min) with progressive increase over time. Uptake of activity in the brain was greater than the system A substrate (R)-[18F]MeFAMP but lower than the system L substrate [18F]FET. Tumor to brain ratios for (S)-[18F]FAMPe ranged from 8 to 12 which are lower than those obtained with (R)-[18F]MeFAMP but higher than with [18F]FET. These in vivo data combined with in vitro cell uptake assays suggest combined transport of (S)-[18F]FAMPe by system A and system L.

CONCLUSION

A novel non-natural 18F-labeled amino acid, (S)-[18F]FAMPe has been facilely prepared in good yields. Biodistribution results suggest that mixed system A/system L substrates can provide relatively high tumor to brain ratios while still being able to cross the BBB. Future efforts include the development of analogues of (S)-[18F]FAMPe and assessment of their imaging properties through small animal PET studies.

CLINICAL RELEVANCE/APPLICATION

18F-labeled amino acids that target system A and system L transporters have the potential to provide superior brain tumor visualization compared to PET tracers targeting system L transport.

SSM14 Molecular Imaging (New Tracers, Contrast Agents, Cell Labeling Methods)

Scientific Papers MI AMA PRA Category 1 Credits ™: 1.00 ARRT Category A+ Credit: 1.00 Wed, Dec 3 3:00 PM - 4:00 PM Location: S504CD

Participants Moderator James P. Basilion PhD : Research Consultant, AKrotome Imaging Inc Stockholder, AKrotome Imaging Inc Research Grant, AKrotome Imaging Inc Moderator Jan Grimm MD, PhD : Research Consultant, Progenics Pharmaceuticals, Inc Shareholder, Nortis, Inc

Sub-Events SSM14-01 Gd-DOTA Decorated Amphiphilic Dextran Nanoparticles as Sensitive MRI Probes Chunchao Xia (Presenter): Nothing to Disclose , Hua Ai PhD : Nothing to Disclose , Bin Song MD : Nothing to Disclose , Qiyong Gong : Nothing to Disclose , Changqiang Wu : Nothing to Disclose , Bingbing Lin : Nothing to Disclose , Danyang Li : Nothing to Disclose PURPOSE

Magnetic resonance imaging (MRI) has shown its advantages in early diagnosis, drug discovery, medical implant evaluation and other important noninvasive imaging monitoring processes.1, 2 However, the sensitivity of free gadolinium complexes, such as Gd-DOTA, are poor for cellular and molecular imaging. One facile option to increase the sencitivity is conjugation of Gd(III) complexes on rigid macromolecules or nanoparticles.3 In this study, polymeric micelles of amphiphilic starlike dextran was used as nanoplatforms for conjugation of Gd-DOTA to form polymer nanoparticles with multivalent Gd-DOTA on their surface (Scheme 1). The T1 relaxivity was characterized under a clinical 1.5T MRI scanner and showing much higher sensitivity than free Gd-DOTA complexes.

METHOD AND MATERIALS Methods: Amphiphilic starlike dextran β-CD-Dex-g-SA/alkyne was synthesized following a "coupling onto" approach via the click chemistry reaction between heptakis-6-azido-6-deoxy-β-cyclodextrin and alkyne dextran according to the previous reference.4 Multiple Gd-DOTA-N3 molecules were then grafted onto the surface of micelles of β-CD-Dex-g-SA/alkyne in water. T1 relaxivities of the multivalent micelles and Gd-DOTA complexes were measured at 1.5 T under a clinical MRI scanner (Siemens Sonata). Macrophages and other cell lines labeled with this multivalent probes were imaged under a 3T clinical MRI scanner.

RESULTS Amphiphilic starlike dextran β-CD-Dex-g-SA/alkyne was synthesized and characterized by 1H NMR. SEM and DLS data shows that it can assemble into micelles with a diameter of ~100 nm. T1 relaxivity of the resulted multivalent Gd-DOTA nanoparticles and free Gd-DOTA in water was shown in Figure 1, β-CD-Dex-g-SA/Gd-DOTA nanoparticles has a much higher T1 relaxivity of 18.1 Gd mM-1s-1 than that of Gd-DOTA (4.0 Gd mM-1s-1). Cells labeled with this multivalent probes have shown strong contrast against unlabeled cells under a 3T clinical MRI scanner (Figure 2).

CONCLUSION β-CD-Dex-g-SA/Gd-DOTA nanoparticles as a sensitive MRI probe via rigid triazole ring of click chemistry were successfully prepared. T1 relaxivity of the probe was increased by almost 350% compared to that of free Gd-DOTA. Cells labeled with the probe also have shown strong contrast against unlabeled cells.

CLINICAL RELEVANCE/APPLICATION

Gd-DOTA decorated amphiphilic dextran nanoparticles with much higher sensitivity than free Gd-DOTA are potential MRI probes used for cellular and molecular imaging.

SSM14-02 Targeted CT/MR Dual Mode Imaging of Tumor Cells Using Multifunctional RGD Conjugated Dendrimer-entrapped Gold Nanoparticles Han Wang MD, PhD (Presenter): Nothing to Disclose , Qian Chen : Nothing to Disclose , Lin-Feng Zheng MD, PhD : Nothing to Disclose , Xiang-Yang Shi : Nothing to Disclose , Gui-Xiang Zhang MD : Nothing to Disclose PURPOSE To determine the feasibility of targeted dual mode CT/MR imaging of tumor cells using the thiolated cyclo(Arg-Gly-Asp-Phe-Lys(mpa)) (RGD)-modified multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) as imaging probes.

METHOD AND MATERIALS RGD modified Au DENPs loaded with Gd(III) (Gd-Au DENPs-RGD) was designed for targeted tumor CT/MR imaging applications. G5.NH2 was pre-modified with Gd chelator, targeting ligands RGD via a PEG linker strategy and mPEG. The modified dendrimers were used as templates to entrap Au NPs and to chelate Gd(III) ions, following by acetylation of the remaining dendrimer terminal amines to form Gd-Au DENPs-RGD. The formed Gd-Au DENPs-RGD probes were characterized via 1HNMR spectroscopy, UV-Vis spectrometry, transmission electron microscopy (TEM), dynamic light scattering (DLS), and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). U87MG and L1210 cells were cultured, then, cytotoxicity assay, cell morphology observation and hemolytic assay were used to evaluate the cytocompatibility and hemocompatibility of the particles. Finally, we investigated the dual mode targeted CT/MR imaging performance for xenografted tumor model in vivo, respectively.

RESULTS The formed Gd-Au DENPs-RGD probes with an Au core size of 3.8 nm are water dispersible, stable under different pH (5-8) and temperature conditions (4 oC-50 oC), and non-cytotoxic at an Au concentration up to 100 μM, and display high X-ray attenuation intensity and reasonable r1 relaxivity. Importantly, Gd-Au DENPs-RGD are able to be used as dual mode nanoprobes for specifically targeted CT/MR imaging of xenografted tumor model in vivo via ΑvΒ3 receptor-mediated active targeting pathway after intravenous administration.

CONCLUSION Results of this study indicate that multifunctional Gd-Au DENPs-RGD could be used as promising dual mode nanoprobes for specifically targeted CT/MR imaging of different types of cancer overexpressing ΑvΒ3 integrin.

CLINICAL RELEVANCE/APPLICATION We anticipate that the dendrimer-modified Gd-Au nanoparticles (Gd-AuNPs) should be able to find promising applications in targeted CT/MR imaging of tumor cells in vitro and in vivo.

SSM14-03 Radiolabeling and Biological Evaluation of a Novel 76Br-labeled Amino Acid, BrVAIB, for PET Imaging of Brain Tumors Jennifer Lynn Burkemper PhD (Presenter): Nothing to Disclose , Chaofeng Huang PhD : Nothing to Disclose , Amanda Klaas : Nothing to Disclose , Deborah Sultan : Nothing to Disclose , AIXIAO LI : Nothing to Disclose , Liya Yuan MD : Nothing to Disclose , Efrem Mebrahtu : Nothing to Disclose , Keith M. Rich MD : Nothing to Disclose , Jonathan Edward McConathy MD, PhD : Speakers Bureau, Eli Lilly and Company Research Consultant, Eli Lilly and Company Research Consultant, General Electric Company Research Consultant, Blue Earth Diagnostics Ltd Research Consultant, Siemens AG , Suzanne Elizabeth Lapi PhD : Nothing to Disclose PURPOSE

Many cancers show an upregulation of nutrient transport including amino acid transporters to meet their altered metabolism. System A amino acid transporters are capable of concentrating substrates within cells which can provide higher tumor to background ratios and prolonged retention in tumors which are desirable properties for oncologic imaging agents. The purpose of this work is to exploit these properties of system A transport by synthesizing and radiolabeling the novel 76Br derivative of bromo vinyl amino isobutyric acid (BrVAIB), an analogue of the known radioiodinated (123/131I) system A tracer, IVAIB. The longer half-life of 76Br (16.2 hr) and positron emission makes this radionuclide of interest for long distance distribution and imaging at later time points.

METHOD AND MATERIALS Starting with enantiopure N-boc-α-methyl-L-serine, the vinyl-trimethyl tin precursor needed for labeling, was synthesized in 4 steps. Radiobromination was carried out using peracetic acid and [76Br]NH4Br in water. The labeled compound was fully deprotected and isolated using ion-retardation resin in series with a C-18 sep pak cartridge. Compound purity and identity was verified using iTLC and radioHPLC. [76Br]BrVAIB was injected i.v. into mice with subcutaneous DBT tumors for biodistribution (5 time points, n = 4) and into mice with intracranial gliomas (n = 4) for small animal PET studies.

RESULTS [76Br]BrVAIB was readily labeled and isolated in a 55% yield (> 99% purity). Biodistribution studies showed average maximal tumor uptake between 30 min and an hour, post-injection, at 3.8 + 0.9 and 3.7 + 0.4 %ID/gram, respectively. After 3 hours, BrVAIB had cleared most other measured organs, with the tumor still retaining 1.6 + 0.4 %ID/gram. PET images clearly show uptake in the right, frontal region of the brain in 3 of the mice at 3 hr p.i. and can still be seen at 24 hr.

CONCLUSION

(S)-[76Br]BrVAIB can easily be synthesized and radiolabeled in good yields and shows modest uptake and retention in intracranial DBT glioma tumors. Future work will include evaluation of the N-methyl amino analogue of BrVAIB which may have more selectivity for system A transporters and prolonged retention in tumors.

CLINICAL RELEVANCE/APPLICATION

A 76Br-labeled amino acid will provide a longer-lived alternative to 11C- and 18F-labeled system A tracers, facilitating distribution to remote sites for imaging at later time points post injection.

SSM14-04 Immunomodulation by Co-Transplanted Mesenchymal Stem Cells Improves Survival of Glial-Restriced Progenitors Amit Srivastava : Nothing to Disclose , Camille Bulte : Nothing to Disclose , Irina Shats : Nothing to Disclose , Piotr Walczak : Nothing to Disclose , Jeff W.M. Bulte PhD (Presenter): Research Grant, Koninklijke Philips NV Founder and co-owner, SenCEST, LLC PURPOSE

Loss of functional cells from immunorejection during the immediate post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that mesenchymal stem cells (MSCs) exhibit many positive effects when engrafted, including immunomodulation. We investigated whether co-transplantation of MSCs could improve the survival of transplanted therapeutic cells.

METHOD AND MATERIALS Glial-restricted progenitors (GRPs) were isolated from luciferase-transgenic FVB mouse brain (at E13.5 stage). MSCs were isolated from BALB/c mouse bone marrow. Twenty immunocompetent BALB/c and eight immunodeficient Rag2-/- mice (used as control) were intracerebrally transplanted, either with GRPs alone (1x105 cells), or GRPs co-transplanted with MSCs (1x105 cells). No immunosuppression was given. Bioluminescence imaging (BLI) and computed tomography (CT) were performed for 21 days post-transplantation using a PerkinElmer IVIS Spectrum/CT. Immunohistochemical assays were performed to detect inflammation and survival of transplanted cells.

RESULTS Three-dimensional images generated by co-registering BLI and CT images confirmed the placement of the cells at the site of targeted injection in the brain (Fig. 1A). Normalization of BLI signal intensity with day 1 revealed that on day 21, signal intensity had decreased 96% in animals transplanted with GRPs alone versus 68% in animals co-transplanted with MSCs (p<0.05) (Fig. 1B). On histology, co-transplantation of MSCs effectively suppressed the host immune response against the graft. In the immunodeficient animals, all transplanted GRPs survived regardless whether MSCs were co-transplanted.

CONCLUSION

In immunocompetent mice without immunosuppression, co-transplantation of MSCs creates a microenvironment that is more conducive to the survival of allogeneic GRPs.

CLINICAL RELEVANCE/APPLICATION MSCs are already used clinically in a variety of degenerative diseases (i.e., myocardial infarct, multiple sclerosis, and stroke). We show that co-transplantation of MSCs can also improve the survival of other therapeutic cells, which opens up new avenues in stem cell therapies for neuroinflammatory disease.

SSM14-05 A Comparative Evaluation of CCD-based Beta Imaging and Cerenkov Luminescence Imaging Martin T. King MD, PhD (Presenter): Nothing to Disclose , Colin Carpenter : CEO, Siris Medical Systems , Conroy Sun : Nothing to Disclose , Xiaowei Ma : Nothing to Disclose , Guillem Pratx : Nothing to Disclose , Lei Xing PhD : Research Grant, Varian Medical Systems, Inc PURPOSE

Although Cerenkov luminescence imaging (CLI) is a validated method for imaging FDG-avid tumors, CLI suffers from low sensitivity. CCD-based beta imaging is an alternative modality, which incorporates a scintillator for improving sensitivity. In this abstract, we conduct a comparative evaluation of beta imaging with CLI.

METHOD AND MATERIALS We performed all experiments on a commercial small animal imager. For the scintillator, we used a radioisotopic screen. Each beta image was calculated as the difference between two images: 1) a 'gamma + beta' image with a scintillator between the object and the camera, and 2) a 'gamma' image with a 1 mm steel slab (>97.4% beta rejection from Tl-204) between the scintillator and the object. Exposure times for CLI and beta images were 180 s and 10-30 s, respectively. For in vitro FDG experiments, we obtained CLI and beta images of the following: a uniform source (100 uCi), a resolution phantom (1.2-4.8 mm rods), a 1.0 mm diameter capillary tube (100 uCi), and serial 10-fold dilutions of FDG droplets (10 uCi to 0.001 uCi ) in 50 uL matrigel. For in-vivo experiments, we imaged 5 nude mice inoculated with B16F10-luciferase expressing mouse melanoma cells. After excising the skin, we obtained a beta image, a CLI image, and a bioluminescence (BLI) image. We computed signal-to-background ratios (SBRs) for each modality. We then applied a dependent t-test to compare the SBRs between CLI and beta images.

RESULTS

For the uniform source, beta imaging provided 227 fold more counts-per-second than CLI. Beta imaging could not resolve any rods on the resolution phantom, whereas CLI could resolve rods at all diameters. For the capillary source, full-width-at-half-maximums for the beta and CLI images were 3.9 and 1.0 mm, respectively. For the FDG dilutions, beta imaging and CLI could detect 0.01 uCi and 0.1 uCi droplets, respectively, at SBRs greater than 1.5. For the in-vivo experiments, the average SBR was 16.1 +/- 11.2 for BLI, 2.1 +/- 1.6 for CLI, and 4.3 +/- 2.7 for beta images. SBRs for CLI and beta images were statistically different on dependent t-test (p = 0.05).

CONCLUSION

CCD-based beta imaging is more sensitive than CLI in both in vitro and in vivo models, but exhibits decreased spatial resolution.

CLINICAL RELEVANCE/APPLICATION

CCD-based beta imaging can image FDG-avid tumors in a clinically feasible timeframe. This modality potentially may be used for FDG-guided surgery or endoscopy.

SSM14-06 Dual-Modality, Fluorescent, PLGA-Encapsulated Bismuth Nanoparticles: A Novel Nanoparticle Platform for Molecular and Cellular Computed Tomography Christiane Mallett PhD (Presenter): Nothing to Disclose , Dorela D. Shuboni PhD : Nothing to Disclose , Aaron Schwartz-Duval : Nothing to Disclose , Eric Swy : Nothing to Disclose , Matthew T. Latourette BS : Nothing to Disclose , Maciej Parys DVM : Nothing to Disclose , David Peter Cormode DPhil, MS : Research Grant, Koninklijke Philips NV Consultant, Koninklijke Philips NV , Erik M. Shapiro PhD : Nothing to Disclose PURPOSE

High Z metal nanoparticles (NPs) have the potential to shift the use of CT from structural to molecular imaging. Bismuth (Bi) has a high k-edge, low cost of production and low toxicity. We conducted in vitro and in vivo assays to determine the toxicity, clinical manifestations and imaging efficacy of polymer-encapsulated Bi NPs.

METHOD AND MATERIALS 40 nm pure Bi nanocrystals were synthesized and characterized, then encapsulated into poly(lactic-co-glycolic)acid (PLGA) NPs with or without coumarin for fluorescence. In vitro, we assessed Bi nanocrystal and NP dissolution at pH 7 and 5.5 for 42 days and the effect of the NPs on cell proliferation. Ex vivo μCT and fluorescence imaging was performed on a piece of chicken meat injected with NPs. For in vivo toxicology, Sprague-Dawley rats were injected IV or IP with NPs at 2 and 20 mg Bi/kg. Blood was collected for analysis of serum chemistry and hematology, and organs were collected for histopathology. For in vivo μCT, NPs in PBS at 160 or 550 mg/kg were injected retro-orbitally and the mice were scanned 1-24h post-injection.

RESULTS After 24h, NPs (~120 nm, 60% Bi w/w) were 70% dissolved at pH 5.5; there was negligible dissolution at pH 7 on d42. Cell proliferation was unaffected at the lowest Bi concentrations but was reduced at 10-1000 μg/mL. In on d42. Cell proliferation was unaffected at the lowest Bi concentrations but was reduced at 10-1000 μg/mL. In vivo, there were no clinically significant changes in blood measures. Histopathology found mild kidney damage and recovery in one rat that received 20 mg/kg NPs IV. Ex vivo, the μCT and coumarin signals were exactly overlaid. With in vivo μCT, Bi contrast was detected in the liver and spleen of the mice. There were some adverse effects at doses ten times higher than anticipated for targeted molecular imaging studies.

CONCLUSION

Fluorescent/CT dense coumarin-Bi NPs were fabricated and in vivo CT imaging demonstrated. Toxicity was minimal except at high doses. Strategies for reducing the rapid rate of Bi dissolution from Bi-PLGA NPs, and PEG-ylation to reduce renal clearance, should be explored to minimize toxicity at high doses. For molecular imaging with this agent, the particles will be targeted to specific cellular targets and the route of delivery optimized to achieve a high local and lower systemic dose of bismuth.

CLINICAL RELEVANCE/APPLICATION Polymer encapsulated Bi NPs are a novel technological platform for molecular and cellular CT, and their low cost and minimal toxicity are enabling for potential clinical applications.

VSNR51 Neuroradiology Series: Brain Tumors

Series Courses

OI NM MI BQ NR AMA PRA Category 1 Credits ™: 3.25 ARRT Category A+ Credits: 3.75 Thu, Dec 4 8:30 AM - 12:00 PM Location: N228

Participants Moderator Rivka Rachel Colen MD : Nothing to Disclose Moderator Timothy Roberts PhD : Nothing to Disclose

Sub-Events VSNR51-01 Brain Tumor Imaging-from Structure to Individual Biology Soonmee Cha MD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Review current state-of-the-art MR imaging techniques for diagnosis and management of brain tumors. 2) Describe recent progress and advances in molecular genetics of brain tumors and illustrate how these advances impact imaging interpretation. 3) Present strengths and pitfalls of advanced physiologic MR imaging techniques in the assessment of tumor activity following therapy.

VSNR51-02 Identification of Glioblastoma Radiophenotypes in Patients with 1p/19q Co-deletion Ahmed M. Amer MD : Nothing to Disclose , Ginu A. Thomas MBBS : Nothing to Disclose , Jixin Wang PhD : Nothing to Disclose , Pascal O. Zinn MD : Nothing to Disclose , Rivka Rachel Colen MD (Presenter): Nothing to Disclose PURPOSE

To create an imaging genomic biomarker signature in order to identify those Glioblastoma patients (GBM) with 1p/19q deletion. Recent prospective randomized clinical trials have validated correlations between 1p/19q codeletion and increased overall survival of patients treated with radiation therapy with or without chemotherapy

METHOD AND MATERIALS Using The Cancer Genome Atlas (TCGA),we identified 99 treatment naive GBM patients for whom both gene and miRNA expression profiles including the 1p/19q codeletion status, and pretreatment brain MR Imaging from The Cancer Imaging Archive(TCIA) were available. The VASARI feature set and 3D Slicer software 3.6 (http://www.slicer.org) were used for image analysis and image review was done in consensus by 2 neuroradiologists. Fluid Attenuated Inversion Recovery (FLAIR) was used for segmentation of the edema/cellular infiltration and Post GD T1-weighted imaging (T1WI) for segmentation of tumor enhancement and necrosis. Imaging parameters were then correlated with 1p/19q deletion status and gene expression profiles. Multiple complex biomarker signatures based on gene profiling and survival were created.

RESULTS

A novel imaging biomarker signature using multiple imaging parameters predicted 1p/19q co-deletion in patients with GBM. These were also associated with overall survival and progression-free survival. CONCLUSION

Imaging genomic signatures can be expected to promote a more robust personalized approach to patient care and accelerate drug development and help stratify patients in clinical trials. An imaging biomarker signature was created using both qualitative and quantitative imaging parameters that predicted 1p/19 deletion status and expression.

CLINICAL RELEVANCE/APPLICATION

Prediction of 1p/19q status promotes a more effective personalized therapy and help stratify patients in clincial trials

VSNR51-03 Longitudinal 3D MR Spectroscopic Imaging of 2-Hydroxyglutarate in Patients with Mutant IDH1 Glioma Undergoing Radiochemotherapy Ovidiu C. Andronesi MD, PhD (Presenter): Nothing to Disclose , Franziska Loebel MD : Nothing to Disclose , Wolfgang Bogner MSC : Nothing to Disclose , Malgorzata Marjanska PhD : Nothing to Disclose , Elizabeth Gerstner MD : Nothing to Disclose , Andrew S Chi MD,PhD : Nothing to Disclose , Tracy T. Batchelor MD : Nothing to Disclose , Daniel P Cahill : Nothing to Disclose , Bruce R. Rosen MD, PhD : Research Consultant, Siemens AG PURPOSE

The hallmark metabolic alteration of mutant IDH gliomas is the production of 2-hydroxyglutarate (2HG) which may play a central role in downstream effects. Hence, 2HG may be an ideal biomarker for both diagnosing IDH mutations and monitoring response to treatment. 2HG can be measured in-vivo by magnetic resonance spectroscopy and there is significant interest in developing methodology that performs reliably in patients. Here we present results obtained with a new 3D MR spectroscopic imaging (MRSI) sequence that maps 2HG over the entire volume of the tumor during treatment.

METHOD AND MATERIALS A robust 3D MRSI sequence for 2HG imaging was newly developed by integrating adiabatic J-difference spectral editing, spiral imaging, and real-time motion correction. The acquisition parameters were: TR=1.6s, TE=68ms, FOV=200x200x200 mm3, acquisition matrix 10x10x10, NA=20, acquisition time TA=9:55 min:s. Spectra were fitted with LCModel software. Measurements were performed on a 3T MR scanner. 3D MRSI was performed in 20 patients with mutant IDH1 gliomas (WHO grades II-IV) consented with an approved IRB protocol. A baseline scan was done after surgery and before start of adjuvant treatment. At the moment 9 patients have completed a second post-treatment scan. Adjuvant treatment included radiotherapy and/or chemotherapy. The post-treatment scan was done in a time interval of 1-3 months after treatment.

RESULTS Detectable levels of 2HG were measured in all patients that did not have gross total resection of tumor. 3D metabolic maps were obtained for 2HG, choline, N-acetyl-aspartate, glutamate-glutamine, and lactate. In 9 patients who have undergone both pre- and post-treatment scans, 4 demonstrated marked decrease (30-50%) in the levels of 2HG after completion of adjuvant therapy as shown in Figure 1. The remainder showed partial reduction of 2HG, with no patients showing increased 2HG levels.

CONCLUSION

We demonstrate for the first time that 3D imaging of 2HG is clinically feasible in patients with IDH1 mutated gliomas. Quantification of 2HG levels in a cohort of mutant IDH glioma patients shows measurable changes during treatment.

CLINICAL RELEVANCE/APPLICATION

2HG imaging could be used to answer clinically important questions of true-/pseudo-response and true-/pseudo-progression in mutant IDH glioma patients. 3D mapping of 2HG and other metabolites is important to capture tumor heterogeneity and reduce variability in longitudinal studies.

VSNR51-04 Prognostic Value of ADC and Its Correlation with Methylguanine-DNA- Methyltransferase (MGMT) Promotor Methylation Status and Epidermal Growth Factor Receptor (EGFR) Amplification and Survival in Glioblastoma Multiforme (GBM) Romina Zalazar MD (Presenter): Nothing to Disclose , Miguel David Hernandez Arguello MD : Nothing to Disclose , Maria Paramo Alfaro MD : Nothing to Disclose , Pablo Daniel Dominguez MD : Nothing to Disclose , Jose Luis Zubieta : Nothing to Disclose , Jose luis solorzano : Nothing to Disclose , Paula Barquin Garcia MD : Nothing to Disclose , Maria De Los Reyes Garcia de Eulate : Nothing to Disclose PURPOSE

To analyse whether apparent diffusion coefficient (ADC) values correlate with survival and with methylguanine-DNA-methyltransferase (MGMT) promoter methylation status and epidermal growth factor receptor (EGFR) amplification on glioblastoma multiforme (GBM).

METHOD AND MATERIALS 72 patients with untreated GBM before surgery were analysed (mean time MRI-Surgery=6 days). Patients were followed-up for at least 12 months or until death. A ROI were drawn on ADC-map in the highest restriction region of the tumor and on the normal-appearing contralateral white matter (NCWM). ADCmin-values and ADC-index defined as a ratio between tumoral ADCmin and NCWM-ADCmean were evaluated. MGMT-status(n=60), EGFR amplification(n=53), KPS, tumoral and residual volume, progression-free survival (PFS) and overall survival (OS) were analysed. Kaplan-Meier and Cox-regression model were performed.

RESULTS 53 patients had complete resection. Presurgical and post-surgical mean tumoral volume were 42.4cm3 and 0.57cm3 respectively. Non methylated-MGMT-status(n=27) and low ADC values (<0.7) correlates with a decrease in PFS and OS (p<0.001). EGFR amplification (n=19) was correlated with a decrease in PFS (p=0.029) only when low ADC values and non--methylated-MGMT-status were present. EGFR amplification was not correlated with a poor outcome in the group of higher ADC values and MGMT methylated status (p<0.001). On Kaplan-Meier analyses MGMT-status correlated better with PFS (p=0.002), while ADC values correlate better with OS (p 0.001). In the multivariate analysis low ADC values and MGMTNM status were significant predictors of prognosis when they were adjusted by clinical variables (p= 0.001 and p=0.037, respectively).

CONCLUSION

The combined use of ADC values and MGMT-status are stronger predictors than using separated in GBM and could modulate outcome in patients with EFGR amplification.

CLINICAL RELEVANCE/APPLICATION

ADC values in GBM correlates significantly with survival, independently of the MGMT and EGFR status .Therefore, ADC values could be used as independent predictors of survival in those patients.

VSNR51-05 Automated Task-Free Resting-State Functional MRI to Define Critical Margins in Surgical Planning for Brain Tumor Surgery Wolfgang Gaggl PhD (Presenter): Researcher, Prism Clinical Imaging, Inc , Svyatoslav Vergun : Nothing to Disclose , Matthew Andreoli : Nothing to Disclose , Veena A. Nair PhD : Nothing to Disclose , Vivek Prabhakaran MD, PhD : Nothing to Disclose PURPOSE

Resting state functional MRI (rs-FMRI) enables clinicians to define critical areas and margins for pre-surgical planning of brain tumor resections without requiring the active participation of the patient. While task-based FMRI has gained utility in the clinical environment, rs-FMRI needs to be automatized and verified in tumor patients to be useful as a reliable clinical tool.

METHOD AND MATERIALS

Data were acquired from 48 patients (24 with brain tumors, 24 epilepsy and vascular lesions) including rs-FMRI, task-based FMRI, diffusion tensor imaging (DTI) and structural MRI on 1.5T and 3T MRI scanners. Data were preprocessed (Allen EA, 2011) using AFNI (NIH, Bethesda, MD) and FSL (Oxford, UK) and decomposed into individual functional network components using independent component analysis (ICA) implemented in the GIFT toolbox (MRN, Albuquerque, NM) calculated for 28 and 75 components. ICA components were both manually identified by a trained radiologist overlaid on the anatomical and DTI images and compared by spatial correlation to published template components from healthy subjects (Calhoun, 2008). Predictive values from radiologist vs. automation where generated as well as ranked cross-correlation values.

RESULTS

Reproducible ICA components could be identified from both the 28 and 75 component analyses. Higher component numbers resulted in higher spatial detail and higher classifier values, but occasionally led to functional networks distributed across several components. The median classifier achieved better than 80% agreement. Using the non-deformable MNI registration to warp templates into subject space, templates showed considerable overlap with the tumor in some instances. Calculated ICA components, however, followed the outline of the tumor highlighting functional gray matter as classified by a clinician.

CONCLUSION

Our automated classification allows extraction of functional network components quickly with good agreement to the manual reader and with seamless integration into the existing clinical FMRI workflow. A larger functional component template library for use with clinical patient populations is currently underway for further validation and improvement of classification accuracy.

CLINICAL RELEVANCE/APPLICATION

Task-free functional MRI can aid in identification of eloquent brain tissue in tumor resections by outlining functional networks and critical margins where active patient participation is not possible. VSNR51-06 Role of the Radiologist in Pre-op Brain Tumor Mapping John L. Ulmer MD (Presenter): Stockholder, Prism Clinical Imaging, Inc Medical Advisory Board, General Electric Company LEARNING OBJECTIVES

1) Discuss the differences between image-centric and patient-centric perspectives in clinical Neuroradiology and presurgical brain mapping. 2) Cite the utility of clinical assessments and the electronic medical record in presurgical brain mapping. 3) Discuss the impact of presurgical brain mapping on surgical decision making.

VSNR51-07 Imaging Biomarkers of CNS Tumor Treatment Response Benjamin Michael Ellingson MS, PhD (Presenter): Research Consultant, MedQIA Imaging Core Laboratory Research Consultant, F. Hoffmann-La Roche Ltd Research Consultant, Tocagen Inc Research Consultant, Boston Scientific Corporation Research Consultant, Amgen Inc Research Grant, Siemens AG Research Grant, F. Hoffmann-La Roche Ltd LEARNING OBJECTIVES

1) Participants will comprehend the current RANO criteria and its limitations in practice. 2) Participants will comprehend and be able to apply digital T1 subtraction for quantification of tumor response. 3) Participants will gain an appreciation for how to use T2/FLAIR to measure response, challenges associated with T2/FLAIR, and potential solutions for measuring nonenhancing tumor response. 4) Participants will comprehend basic and advanced diffusion MR biomarkers to treatment response. 5) Participants will comprehend basic and advanced perfusion MR biomarkers to treatment response. 6) Participants will comprehend basic pH-weighted MR response using CEST imaging. 7) Participants will comprehend basic and advanced PET imaging response.

ABSTRACT Depths of novel imaging biomarkers are now available for evaluating biological response to new therapies in CNS tumors. The current course will briefly outline the current Response Assessment in Neuro-Oncology (RANO) criteria, including limitations when implementing in multicenter trials. The use of digital T1 subtraction maps as a method for measuring enhancing tumor volume in the presence of agents that reduce vascular permeability will be discussed. T2/FLAIR response, challenges associated with interpreting T2/FLAIR response, and a potential solution for measuring nonenhancing tumor response using T2 relaxometry will be described. This course will outline simple and advanced diffusion MR biomarkers for patient stratification and response assessment, including ADC histogram analysis, functional diffusion mapping, voxel-wise proliferation and invasion modeling, and DREAM-MRI. Simple and advanced perfusion MR biomarkers, including DSC-MRI, DCE-MRI, and a new pharmacokinetic perfusion-diffusion model will be described. The use of pH-weighted MR response to therapy will also be discussed using CEST imaging. Lastly, basic and advanced PET imaging techniques will be described in the context of response assessment and drug target efficacy.

VSNR51-08 The DTI Challenge Initiative on the Standardized Evaluation of DTI Tractography for Neurosurgical Planning Sonia Marie-Aurore Pujol PhD (Presenter): Nothing to Disclose , Alexandra J. Golby MD : Nothing to Disclose , William M. Wells PhD : Nothing to Disclose , Carlo Pierpaoli : Nothing to Disclose , Laurent Chauvin MS : Nothing to Disclose , Hatsuho Mamata MD, PhD : Nothing to Disclose , Guido Gerig : Nothing to Disclose , Martin Styner : Nothing to Disclose , Isaiah Norton : Nothing to Disclose , Sylvain Gouttard : Nothing to Disclose , Caroline Brun : Nothing to Disclose , Olivier Commowick PhD : Nothing to Disclose , Guang Cheng : Nothing to Disclose , Gabriel Girard : Nothing to Disclose , Alessio Moscato : Nothing to Disclose , Maged Goubran BMedSc : Nothing to Disclose , Ye Li : Nothing to Disclose , Ali R. Khan PhD : Nothing to Disclose , Jeremy Lecoeur PhD : Nothing to Disclose , Riza Guler : Nothing to Disclose , Jan Klein PhD : Nothing to Disclose , Joy Matsui : Nothing to Disclose , Yoshitaka Masutani PhD : Nothing to Disclose , Sudhir Pathak : Nothing to Disclose , Peter Neher : Nothing to Disclose , Hesamoddin Salehian : Nothing to Disclose , Aymeric Stamm : Nothing to Disclose , Manabu Tamura : Nothing to Disclose , Wendy Shi : Nothing to Disclose , Antonio Tristan MSC : Nothing to Disclose , Sinchai Tsao MS : Nothing to Disclose , Gopalkrishna Veni : Nothing to Disclose , Carl Fredrik Westin PhD : Nothing to Disclose , Yasukazu Kajita : Nothing to Disclose , Xiaolei Chen : Nothing to Disclose , Yoshihiro Muragaki : Nothing to Disclose , Arya Nabavi MD : Nothing to Disclose , Ron Kikinis MD : Nothing to Disclose PURPOSE To provide standardized evaluation of Diffusion Tensor Imaging (DTI) tractography algorithms for mapping white matter pathways during glioma resection

METHOD AND MATERIALS Nineteen tractography teams reconstructed the corticospinal (CST) tract on a series of 11 cases presenting with a glioma near the motor cortex area (high-grade n=7, low-grade n=4), in the three editions of the DTI Tractography Challenge at the MICCAI 2011,2012 and 2013 conference. The datasets included DTI scans (20 and 30 gradient directions, b-value=1000 s/mm2) acquired on a 3T scanner, and co-registered T1-weighted and FLAIR scans with segmented tumor and edema. Participating teams were required to submit part of their tractography results prior to the workshop, and to process two cases in a limited time at the event. Five neurosurgeons and four DTI experts evaluated and discussed the tractography reconstructions using a web-based questionnaire with standardized views of the tractography results. Variability among methods was quantified based on the Dice coefficient of bundle overlap of the voxelized tracts.

RESULTS The 232 corticospinal tracts submitted to the three editions of the DTI Challenge workshop showed a large inter-algorithm variability (average Dice coefficient of overlap: 0.23(tumor), 0.22(contralateral)). Standardized review of the results demonstrated that most algorithms could reconstruct the CST projection to the cortical motor foot area and identified limitations in the ability of some methods to track the lateral projections to the face and hand areas, as well as false-negative and false-positive tracts in both hemispheres. Improvements of the tractography reconstructions from year 1 to year 3 indicate this collaborative effort is a learning experience for the community.

CONCLUSION DTI tractography reconstructions are complex geometric models of white matter anatomy that can provide clinically relevant information for the planning of glioma resection in eloquent areas. By providing a benchmark for the standardized evaluation of tractography algorithms on a common series of clinical data, the DTI tractography challenge initiative aims to accelerate the translation of novel tractography tools from research to the clinics.

CLINICAL RELEVANCE/APPLICATION Standardized evaluation of DTI tractography techniques can help establish the validity of tractography-derived information to assist in neurosurgical decision-making.

VSNR51-09 Distinguishing Pseudoprogression from True Progression or Recurrence of Malignant Glioma Using Amide Proton Transfer MR Imaging Bo Ma : Nothing to Disclose , Xiaohua Hong : Nothing to Disclose , Meiyun Wang MD, PhD : Nothing to Disclose , Hong Zhang MD : Nothing to Disclose , Jaishri Blakely MD : Nothing to Disclose , Jinyuan Zhou PhD (Presenter): Nothing to Disclose PURPOSE

Amide proton transfer (APT) imaging is a novel molecular imaging approach that generates MRI contrast based on endogenous cellular proteins in tissue. The purpose of this study was to determine whether APT imaging can distinguish pseudoprogression from true progression or recurrence in patients with malignant glioma.

METHOD AND MATERIALS

Total 53 patients with pathologically confirmed high-grade gliomas (anaplastic astrocytoma or glioblastoma) were assessed. All patients provided written informed consent as required. Eligibility criteria included: treated with concurrent chemotherapy and radiation therapy (CCRT) after surgical resection, developed new or enlarged contrast enhanced lesions after CCRT, and had standard clinical MRI before and after CCRT. APT-MRI scanning was performed at 3T (3D sequence; 15 slices; 4.4 mm thickness). APT-weighted MRI signals were calculated using magnetization transfer ratio asymmetry at 3.5ppm with respect to water. MRI analysis was made, blinded to pathologic diagnosis, based on longitudinal signal changes in T2W, FLAIR, DWI and gadolinium enhancement on T1W, lasting at least six months.

RESULTS

Longitudinal radiological analysis showed that 39 patients had true progression or recurrence and 14 patients had pseudoprogression. The true progression or recurrence is associated with APT hyperintensity, compared to contralateral normal-appear white matter, while pseudoprogression is associated with APT isointensity to mild hyperintensity. The average APT signal intensity was significantly higher in the true progression/recurrence group (2.76% 0.55%) than in the pseudoprogression group (1.19% 0.40%; P < 0.001). Based on the receiver operating characteristic (ROC) analysis, the cutoff APT signal intensity value was 1.89%, with a sensitivity of 100% and a specificity of 92.9%.

CONCLUSION

The APT-MRI signal may be a valuable imaging biomarker to distinguish between tumor progression or recurrence and pseudoprogression whose diagnosis typically needs repeated surgery or longitudinal MRI scanning over several months.

CLINICAL RELEVANCE/APPLICATION

APT image can help distinguish pseudoprogression from true progression or recurrence. Such a distinction may avoid the time-consuming longitudinal MRI analysis and repeated craniotomy or biopsy.

VSNR51-10 Early Post-Bevacizumab Change in rCBV from DSC-MRI Predicts Overall Survival in Recurrent Glioblastoma Whereas 2D-T1 Response Status Does not: Results from the ACRIN 6677/RTOG 0625 Multi-Center Study Jerrold L. Boxerman MD, PhD (Presenter): Medical Advisor, Imaging Biometrics, LLC , Zheng Zhang PhD : Nothing to Disclose , Kathleen M. Schmainda PhD : Owner, Imaging Biometrics, LLC , Bradley S. Snyder MS : Nothing to Disclose , Melissa Prah BS, MS : Nothing to Disclose , Yair Safriel MBBCh : Principal, PharmaScan Clinical Trials , A. Gregory Sorensen MD : CEO, Siemens USA Consultant, sanofi-aventis Group Research support, sanofi-aventis Group Consultant, Bayer AG Research support, Exelixis, Inc Research support, Schering-Plough Corporation Consultant, Mitsubishi Corporation Consultant, Biogen Idec Inc Research support, Takeda Pharmaceutical Company Limited , Mark Gilbert : Nothing to Disclose , Daniel Paul Barboriak MD : Advisory Board, General Electric Company PURPOSE

ACRIN 6677/RTOG 0625 is a multi-center randomized phase II trial of bevacizumab with irinotecan or temozolomide in recurrent GBM. Pseudoresponse in patients receiving VEGF blockade has raised concerns that conventional MRI may not predict overall (OS) and progression-free survival (PFS). We compared the ability of relative cerebral blood volume (rCBV) from DSC-MRI and post-Gd 2D-T1 MRI after 2 weeks of treatment to predict OS and PFS.

METHOD AND MATERIALS 37/123 patients enrolled consented to DSC-MRI plus conventional MRI, 13 (mean age 54±14 years, 7 men) with DSC-MRI at baseline plus 2 weeks after start of treatment. Two central readers determined response status at 2 weeks using 2D-T1 enhancement and Macdonald threshold criteria with adjudication if necessary. Enhancing ROIs were also defined semi-automatically from thresholded 2D-T1 difference images and used to extract mean GRE (TE=30-40ms) or SE (TE=60-105ms) rCBV (EPI, pre-load, 90° flip angle, post-processing leakage correction) normalized to normal-appearing white matter. Kaplan-Meier survival estimates and log rank test (2-sided) were used to determine if response status on 2D-T1 MRI and rCBV changes on DSC-MRI are predictive of PFS and OS, respectively. Fisher's exact test (2-sided) was used to determine association between change in rCBV and response status on 2D-T1 MRI.

RESULTS

At 2 weeks, there were 3 responders and 10 non-responder/non-progressors (NR-NPs) on 2D-T1, and 4 positive and 9 negative changes from baseline in rCBV. One patient (NR-NP, positive rCBV change) had progressed clinically before week 2 and was excluded from PFS analyses. PFS was significantly worse for patients with increasing vs. decreasing rCBV (p=0.0034), but not for responders vs. NR-NPs (p=0.44). Similarly, survival time was significantly shorter for patients with increasing vs. decreasing rCBV (p=0.0015) but not for responders vs. NR-NPs (p=0.92). There was no significant association between positive vs. negative change in rCBV and responders vs. NR-NPs on 2D-T1 MRI (p=1.0).

CONCLUSION

After 2 weeks of anti-VEGF therapy, change in rCBV from baseline has highly significant prognostic value for PFS and OS, whereas 2D-T1 response status does not.

CLINICAL RELEVANCE/APPLICATION

Early increase in rCBV may be a useful MRI biomarker for the failure of anti-VEGF therapy, permitting a timely switch to alternative trials when necessary. Funded through NCI U01-CA079778 and U01-CA080098.

VSNR51-11 pH-Weighted Molecular MRI of Human Brain Tumors Using Amine CEST Benjamin Michael Ellingson MS, PhD (Presenter): Research Consultant, MedQIA Imaging Core Laboratory Research Consultant, F. Hoffmann-La Roche Ltd Research Consultant, Tocagen Inc Research Consultant, Boston Scientific Corporation Research Consultant, Amgen Inc Research Grant, Siemens AG Research Grant, F. Hoffmann-La Roche Ltd , Robert Harris : Nothing to Disclose , Whitney B. Pope MD, PhD : Research Consultant, F. Hoffmann-La Roche Ltd Research Consultant, Amgen Inc Research Consultant, Tocagen Inc Consultant, Celldex Therapeutics, Inc Consultant, Guerbet SA , Timothy F. Cloughesy MD : Speakers Bureau, Merck & Co, Inc Consultant, F. Hoffmann-La Roche Ltd Consultant, Merck KGaA Consultant, Novartis AG Consultant, Celgene Corporation PURPOSE Acidosis is a hallmark of the tumor extracellular microenvironment. Additionally, studies have shown that tumor regions have increased amino acid uptake in order to meet high metabolic demands. Chemical exchange saturation transfer (CEST) MRI is a non-invasive imaging technique that can provide molecular information about the functional groups of molecules. The CEST signal is sensitive to many factors that affect chemical exchange between molecules, including metabolite concentration and pH. In the current study, we develop and test CEST MRI targeted to the amino acid amine group as a pH-weighted imaging biomarker for identifying cancer tissue in patients with various brain tumors.

METHOD AND MATERIALS Samples of glutamine in water at varying pH (4.0 to 8.6 in units of 0.2) were created at varying concentration. Additionally, samples of phenylalanine and glycine were created for the same pH range. CEST data for these samples were collected at 3T on a Siemens Trio scanner (B1=2μT, 15 100-ms RF saturation pulses, 51 spectral points, ± 5.0 ppm). A normalization image was acquired by setting B1=0. Additionally, serial CEST data for a cohort of 12 GBM patients before, during, and after radiochemotherapy. Image-guided biopsies were obtained in an additional two patients with suspected tumor recurrence.

RESULTS Results show high CEST asymmetry in low pH values between 5.0-7.0 pH and with increasing amino acid concentration. In GBM patients, changes in elevated CEST signal during radiotherapy provided early, independent information regarding the status of the tumor. Some patients showed continual increase in CEST positive regions during therapy, which was followed by early tumor progression (Fig. 1A). In cases of confirmed pseudoprogression, no elevated CEST asymmetry was noted despite an increase in tumor volume on anatomical images (Fig. 1B). Image-guided biopsies of CEST positive locations confirmed tumor, whereas CEST negative regions showed gliosis and little tumor activity.

CONCLUSION CEST MRI targeted to the amine protons may provide a pH-weighted imaging biomarker for identifying regions of active tumor proliferation in patients with brain tumors. CLINICAL RELEVANCE/APPLICATION A non-invasive imaging method for obtaining tissue pH information would be invaluable as a tool for detecting human cancers and characterizing tumor response to therapy.

VSNR51-12 New PET CNS Oncology Approaches Lance T. Hall MD (Presenter): Nothing to Disclose LEARNING OBJECTIVES

1) Review the role of F-18 FDG in brain tumor imaging. 2) Discuss metabolic brain tumor imaging with amino acids and proliferation markers and learn the complimentary information provided to MRI techniques. 3) Introduce novel alkylphosphocholine analogues, CLR1404 and CLR1502, that can be used for PET imaging, in vivo optical imaging, and therapy of brain tumors.

SSQ12 ISP: Molecular Imaging (Prostate Cancer/Bone Metastases)

Scientific Papers NM MI CT GU AMA PRA Category 1 Credits ™: 1.50 ARRT Category A+ Credits: 1.50 Thu, Dec 4 10:30 AM - 12:00 PM Location: S504CD

Participants Moderator Ambros Johannes Beer MD : Nothing to Disclose Moderator Yasuhisa Fujibayashi PhD : Nothing to Disclose

Sub-Events SSQ12-01 Molecular Imaging Keynote Speaker: PET and/or MR Imaging of Bone Metastases Ambros Johannes Beer MD (Presenter): Nothing to Disclose

SSQ12-02 A Phase 2 Study of 99mTc-trofolastat Chloride SPECT to Identify and Localize Prostate Cancer (PCa) in Patients undergoing Radical Prostatectomy (RP) and Extended Pelvic Lymph Node (ePLN) Dissection Compared to Histopathology: An Interim Analysis Kevin Slawin MD (Presenter): Nothing to Disclose , Peter Tenke : Nothing to Disclose , Steven Joniau : Nothing to Disclose , William Ellis : Nothing to Disclose , Boris Alekseev : Nothing to Disclose , Istvan Buzogany : Nothing to Disclose , Sergey Mishugin : Nothing to Disclose , Eric Klein : Nothing to Disclose , Josef Stolz : Nothing to Disclose , Vladimir Student : Nothing to Disclose , Vsevolod Matveev : Nothing to Disclose , Bela Koves : Nothing to Disclose , John Babich PhD : Nothing to Disclose , Hagop Youssoufian : Nothing to Disclose , Nancy Stambler : Nothing to Disclose , Thomas Armor : Nothing to Disclose , Robert Israel MD : Nothing to Disclose PURPOSE

Technetium-99m trofolastat chloride is a novel small molecule SPECT radiotracer with high affinity binding to the external domain of prostate specific membrane antigen (PSMA), an enzyme with high expression in PCa. We conducted an open-label, multicenter study (NCT01667536). The primary endpoint was the ability of trofolastat to detect PCa within the prostate gland (PG). Secondary endpoints included detection in PLNs and comparison to MRI.

METHOD AND MATERIALS Patients (pts) with PCa scheduled for RP with ePLND at high risk (≥cT3 or Godoy nomogram score ≥130) for PLN involvement were eligible. Within 30 days of screening, pts required a bone scan and pelvic MRI. Enrolled pts received trofolastat and SPECT/CT imaging 3-6 hrs later. 3 SPECT/CT readers and one MRI reader, blinded to clinical information, evaluated all available image data. Results were compared to on-site histopathology assessments of RP and ePLN surgical specimens using a common anatomic template. Target to background (T:B) ratio within the PG was measured on the SPECT/CT and compared to Gleason Score (GS).

RESULTS Enrollment has been completed and data is available for the first 54 of 105 pts. A majority of SPECT/CT readers correctly identified the presence of primary PCa in 49/54 (91%) evaluable pts. In 47 pts who had both MR as well as trofolastat scans, readers correctly identified PCa in 40/47 (85%) and 42/47 (89%), respectively. In 37 pts with no prior hormone therapy, GS following RP ranged from 3+4 to 5+5 and significantly correlated with maximum T:B values (r=0.54 p<001). In 17 pts treated with neoadjuvant hormonal therapy, T:B was lower than untreated pts (p<0.005).

CONCLUSION Trofolastat SPECT/CT detected PCa within the PG in 49 of the first 54 (91%) of evaluable high-risk pts prior to surgery. Uptake of trofolastat correlated significantly with GS obtained from post-RP histopathology in untreated pts and may provide information regarding disease aggressiveness using a non-invasive technique in high-risk pts prior to surgery. Final results, analyses of secondary endpoints, pelvic lymph nodes, and comparative performance vs. MRI from this study will be presented.

CLINICAL RELEVANCE/APPLICATION

Accurate detection and characterization of prostate cancer should enhance optimal delivery of therapy. Tc-99m trofolastat has shown clinical relevance in studies to date.

SSQ12-03 A Novel Phase Transition-activatable Multi-Modal Imaging Agent for Prostate Cancer Shadi A. Esfahani MD, MPH (Presenter): Nothing to Disclose , Pedram Heidari MD : Nothing to Disclose , Nazife S. Turker : Nothing to Disclose , Umar Mahmood MD, PhD : Research Grant, Sabik Medical Inc PURPOSE We assessed the ability of a novel phosphatase activatable agent, selective for Prostate Specific Acid Phosphatase (PAP) for the detection of prostate cancer (PCa). Cleavage by PAP results in increased fluorescence and radioactive signal due to a local phase change at sites overexpressing the enzyme.

METHOD AND MATERIALS In vitro, 3 PCa cell lines (AT3-B, LNCaP and PC-3) were incubated with 0.1 mg/ml of the soluble probe 2-(2'-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (127IQ2-P). Dephosphorylation and extracellular precipitation of the probe was assessed using confocal microscope over 24 hrs. PC-3 cells were implanted in 16 nu/nu mice. Epifluorescence imaging (excitation/emission, 480/530 nm) was performed 1 and 24 hrs after IV injection of the probe with concentrations of 1 and 0.1 mg/ml (n=8 each). Signal intensity in xenografts, and tumor to background ratio (TBR) were measured. Biodistribution and histopathologic studies were performed at each time point.

RESULTS In vitro incubation of the probe with all PAP-overexpressing cell lines resulted in phase transition and formation of the corresponding water-insoluble compound in the extracellular space over 24 hrs. In vivo, rapid hydrolysis of the probe within the tumor resulted in peak fluorescence signal intensity and high TBR 1 hr post injection, with non-significant difference between the mean TBR using 2 different probe concentrations [(TBR with 0.1mg/ml: 4.12±0.2 at 1hr vs. 2.45±0.12 at 24 hrs) and (TBR 1mg/ml: 3.44±0.12 in 1 hr, vs. 2.42±0.08 in 24 hrs)]. Biodistribution studies showed rapid probe accumulation in xenografts, fast probe clearance from the background tissues and its excretion through the kidneys.

CONCLUSION Rapid activation, multimodal detection, and high TBR suggest that this phase transition PAP-activatable probe is promising for imaging PCa. This multimodal probe may be employed in early detection of primary and metastatic prostate cancers, treatment response evaluations, and selective image-guided interventions.

CLINICAL RELEVANCE/APPLICATION The phase-transition activatable probe has the potential in early detection and treatment response evaluation of prostate cancer by targeting the diagnostic marker prostate specific acid phosphatase.

SSQ12-04 First Demonstration of Hypofractionated Volumetric Modulated Arc Therapy Dose Painting with Unflattened Beams for Bone Metastases Using 18F-NaF PET/CT scan Yu Kuang PhD (Presenter): Nothing to Disclose , Lili Wu MS : Nothing to Disclose , Mei Li MD : Nothing to Disclose , Liangxi Xie MD, PhD : Nothing to Disclose , Hui Wang PhD : Nothing to Disclose , Xia Li PhD : Nothing to Disclose PURPOSE

Higher radiotherapy (RT) doses delivered to bone metastases would result in a higher local control rate. However, such a high dose is impossible to achieve using conventional RT without an unacceptably high risk of severe toxicity. In this study, we propose, for the first time, to utilize 18F-NaF PET/CT to identify regions within the conventional bone metastasis target volumes that may have different biology and thus allowing RT dose escalation (i.e. dose painting) to attain tumor control.

METHOD AND MATERIALS

Nine patients with bone metastases from prostate cancer who had 18F-NaF PET/CT scan prior to treatment were retrospectively included in this study. Two gross tumor volumes (GTV) were generated for each patient: GTVreg was delineated according to the regular tumor boundary shown in PET/CT images; GTV60% was contoured based on 60% of the maximum SUV values. The planning target volumes (PTVs) were defined as respective GTVs with a 3-mm isotropic expansion margin. Two hypofractionated Volumetric Modulated Arc Therapy (VMAT) plans with 6 MV flattened filter free (FFF) beams (1400MU/min) were generated for each patient based on PTVreg and PTV60%, respectively. The standard plan (Planreg) included a dose of 24 Gy prescribed to PTVreg. The dose escalation plan (Planreg) consisted of a dose of 24 Gy prescribed to PTVreg and a boost dose of 30Gy prescribed to the PTV60%. TCP and the NTCP were also compared between the plans.

RESULTS In all 18 VMAT plans generated, the target volume objectives and the organs-at-risk (OARs) dose constraints were met. The use of pre-treatment 18F-NaF PET/CT led to a better estimate of the dominant lesion areas within routine GTV, which translated into an advantageous escalation of target dose while maintaining normal tissue sparing.

CONCLUSION

This study demonstrates the technical feasibility of 18F-NaF PET/CT-based dose painting for hypofractionated VMAT with FFF beams in patients with bone metastases from prostate cancer.

CLINICAL RELEVANCE/APPLICATION

This molecular image guided VMAT approach, with exquisite tumor metabolic activity arising from 18F-NaF PET, would offer therapeutic insight impossible with the current design. Given the higher dose responsive nature in cancer and the facts that the proposed method requires only minimal protocol modification in routine care, it could have major therapeutic value for the clinical outcome in the long term patient care in the future.

SSQ12-05 Recurrent Prostate Cancer Detection with Anti-3-[18F] FACBC PET-CT: Comparison with CT Oluwaseun Odewole MD, MPH (Presenter): Nothing to Disclose , Funmilayo Tade MD, MPH : Nothing to Disclose , Oyeladun Oyenuga MD, MPH : Nothing to Disclose , Bital Savir-Baruch MD : Nothing to Disclose , Ashesh B. Jani MD : Nothing to Disclose , Osunkoya Adeboye MD : Nothing to Disclose , Raghuveer K. Halkar MD : Research Grant, General Electric Company Research Grant, Gilead Sciences, Inc Royalties, General Electric Company , Peter Nieh MD : Nothing to Disclose , Viraj Master MD : Nothing to Disclose , Mark M. Goodman PhD : Royalties, Nihon Medi-Physics Co, Ltd , David M. Schuster MD : Research funded, Nihon Medi-Physics Co, Ltd Expert Advisory Committee, AIM Specialty Health PURPOSE

To compare the diagnostic performance of the synthetic amino acid analog PET radiotracer anti-3-[18F] FACBC (FACBC) with computed tomography (CT) in the detection of recurrent prostate carcinoma.

METHOD AND MATERIALS

86 patients with suspected recurrent prostate carcinoma after definitive therapy for localized disease and negative bone scan underwent routine diagnostic CT scan and FACBC PET-CT. Correlation to ground truth was made to histology and clinical followup by a multidisciplinary board. Diagnostic performance and scan positivity rates were calculated for both FACBC PET-CT and CT.

RESULTS 83 out of 86 (97%) patients and 67 out of 86 (78%) patients had a reference standard sufficient to determine the presence of prostatic or extraprostatic disease respectively. Mean PSA (±SD) was 6.7 (±6.3) ng/ml. 70 of 86 (81.4%) FACBC scans versus 16 of 86 (18.6%) CT examinations had positive findings suspicious for recurrent disease. At a PSA <1 ng/ml, scan positivity rate for FACBC was 38.5% and CT was 7.7%, while for PSA ≥ 1 scan positivity rate for FACBC was 89.0% and CT was 20.5%. In the prostate bed, FACBC correctly identified 40 more true positive patients than CT (47 vs 7) with a sensitivity of 90.4% for FACBC compared with a sensitivity of 13.2% for CT and a similar positive predictive value (PPV) of 71.2% and 70.0%, respectively [Table1]. For extra-prostatic disease detection, FACBC correctly identified 16 more true positive patients than CT (21 vs 5) with sensitivity of 51.2% for FACBC compared with a sensitivity of 12.5% for CT and a similar PPV of 95.5% and 100%, respectively [Table 1].

CONCLUSION

Anti-3-[18F]FACBC detects more patients with recurrent prostate cancer than CT scan and can better delineate prostatic from extra-prostatic recurrence.

CLINICAL RELEVANCE/APPLICATION

Anti-3-[18F]FACBC is useful for restaging of patients with suspected prostate cancer recurrence.

SSQ12-06 Detection of Intra-pelvic vs Extra-pelvic Lesions with Carbon-11 Acetate Positron Emission Tomography/Computed Tomography Imaging in the Evaluation of Recurrent Prostate Cancer: Interim Results from the AMIC-AC-001 Clinical Study Fabio Almeida MD (Presenter): Nothing to Disclose , Steven Eric Finkelstein MD : Nothing to Disclose , Mark Scholz MD : Nothing to Disclose , Richard Lam MD : Nothing to Disclose , Jeffrey Turner MD : Nothing to Disclose , Elisa Blackwell : Nothing to Disclose PURPOSE

A rising PSA after definitive therapy possess a significant problem, as it represents a large group of prostate cancer (PCa) patients. These patients often have the absence of sufficiently detectable disease on standard imaging studies, thereby limiting treatment options. METHOD AND MATERIALS 373 C11-Acetate (CA) PET/CT studies were reviewed in an ongoing single site FDA/IND clinical study. Male patients with histologically proven PCa and biochemical recurrence (BCR) were imaged. Imaging was performed from vertex - thighs on an integrated PET/CT scanner with imaging 3 to 7 minutes post injection. Detected lesions were defined as moderate-intense focal areas of increased metabolic activity over background in the prostate, bed, nodes and bone.

RESULTS PSA ranged from 0.2 - 148 ng/mL (mean 6.3, median 2.7). The overall detection rate was 87%. At various PSA subgroups the detection rates were: 0.2-0.4 = 50%, 0.41 - 1.0 = 77%, >1.1 90%. True positive (TP) studies were defined as those with positive biopsy, confirmatory imaging or where radiotherapy (RT) was directed at the detected site with a resultant drop in PSA. 145 patients have thus far met criteria for TP analysis, with a PPV of 94%. Focal lesions were detected only in the prostate or bed in 28% (post prostatectomy [RP]: 32%, post RT: 31%, post RP-RT: 11%). In 24% of studies, only focal pelvic nodal lesions were detected (RP:32%, RT:13%, RP-RT: 41%). Lesions where detected in both the prostate/bed and pelvic nodes in 7%. Metabolic lesions were detected in both the pelvis and abdomen in 7% and isolated to abdominal nodes in 3%. Bone lesions were found in 28% of the studies (71% in bone only and 29% with soft tissue lesions). In 3%, lesions where detected in the other areas such as the lungs, mediastinal nodes or in supraclavicular nodes (particularly on the left).

CONCLUSION

In patients with BCR of PCa, CA PET/CT imaging demonstrates a high detection rate and PPV for the site(s) of recurrence/metastasis. Particularly evident is the high detection of locally recurrent and intra-pelvic nodal disease (59%), which may be amenable to focal therapy with a curative intent. CA PET/CT was also able to better identify those with distant metastases, whom would most benefit from systemic therapy.

CLINICAL RELEVANCE/APPLICATION

Conventional imaging is of limited value in BCR PCa and CA PET imaging appears to help differentiate those with local-regional disease from distant metastasis.

SSQ12-07 Comparison of [18F]DCFBC PET/CT to Conventional Imaging Modalities in the Detection of Metastatic Prostate Cancer Steven Patrick Rowe MD, PhD (Presenter): Nothing to Disclose , Katarzyna J. Macura MD, PhD : Nothing to Disclose , Anthony Ciarallo MD, MSc : Nothing to Disclose , Esther Mena : Nothing to Disclose , Amanda Blackford MSc : Nothing to Disclose , Daniel Holt PhD : Nothing to Disclose , Ronnie Mease PhD : Nothing to Disclose , Robert F. Dannals PhD : Nothing to Disclose , Martin Gilbert Pomper MD, PhD : Grant, Eisai Co, Ltd Grant, Eli Lilly and Company Founder, Cancer Targeting Systems, Inc Board of Directors, Cancer Targeting Systems, Inc Founder, Theraly Pharmaceuticals Inc , Steve Cho MD : Nothing to Disclose PURPOSE

Improved methods of imaging metastatic prostate cancer (PCa) are needed given limitations in the conventional imaging modalities (CIM) of bone scan and CT. [18F]DCFBC is a positron-emitting, urea-based small molecule inhibitor of prostate-specific membrane antigen (PSMA) that has been demonstrated to target PCa specifically and can be imaged with PET.

METHOD AND MATERIALS

14 patients with recurrent (PCa) and imaging findings diagnostic of and/or indeterminate for radiographic recurrence were imaged with [18F]DCFBC PET/CT and CIM. Central review was performed with lesion-by-lesion analysis of the PET and CIM. Lesions were scored as positive, equivocal, or negative on each modality. GEE intercept-only regression models that accounted for intra-patient correlation of multiple lesions were used to estimate proportion of agreement in lesion detection between [18F]DCFBC PET/CT and CIM.

RESULTS

673 lesions were identified on at least one modality. Of those lesions that were positive with PET, 45% (95% CI, 28-65%) were negative or equivocal with CIM. This includes 89% (71-96%) of identified lymph node lesions, 24% (13-39%) of bone lesions, and 39% (14-71%) of visceral lesions (though only 24 such lesions were identified). Of those lesions that were positive on CIM, only 6% (2-14%) were negative or equivocal on PET. This includes 8% (1-42%) of lymph node lesions, 8% (3-17%) of bone lesions, and no identified visceral lesions.

CONCLUSION [18F]DCFBC PET/CT identified more potential sites of metastatic PCa than CIM. The majority of lymph node lesions with PET uptake were negative or equivocal with CIM, often due to size <1 cm and hence not deemed definitely pathologic by CT size criteria. Some bone lesions with PET uptake were also not identified on CIM, apparently as a result of lack of significant associated sclerosis. Planned analyses will include clinical and imaging follow-up to diagnose all sites of true PCa metastases definitively in these patients to further assess the utility of this new PET radiotracer.

CLINICAL RELEVANCE/APPLICATION [18F]DCFBC is a novel PET imaging agent that promises to be more sensitive than CIM for detection of metastatic disease in patients with prostate cancer.

SSQ12-08 Optimization of Fluorescence Detection Improves Sentinel Node Localization in Prostate Cancer Patients Nynke S. Van Den Berg MSc (Presenter): Nothing to Disclose , Gijs Kleinjan MD : Nothing to Disclose , Oscar Brouwer : Nothing to Disclose , Cenk Acar : Nothing to Disclose , Esther Wit : Nothing to Disclose , Erik Vegt : Nothing to Disclose , Renato Valdes Olmos : Nothing to Disclose , Fijs Willon Bernard van Leeuwen PhD : Nothing to Disclose , Henk G. Van Der Poel : Nothing to Disclose PURPOSE In 2011 the hybrid tracer indocyanine green (ICG)-99mTc-nanocolloid was introduced for sentinel node (SN) biopsy in prostate cancer patients. This tracer, being both radioactive and fluorescent, the radioguided approach was complemented with fluorescence guidance towards the SN(s). The current study evaluated how intraoperative fluorescence guidance during the hybrid SN procedure could be further optimized, by improving the tracer and by upgrading the fluorescence imaging hardware.

METHOD AND MATERIALS 40 patients with >10% risk of lymph node metastasis (based on Briganti nomogram) were included for a combined SN, extended pelvic lymph node dissection (ePLND) and robot-assisted radical prostatectomy procedure. The hybrid tracer was injected into the peripheral zone of the prostate under transrectal ultrasound guidance. Following preoperative SN mapping (lymphoscintigraphy and SPECT/CT), intraoperative SN identification was achieved using radiotracing and fluorescence imaging. Three patient groups were evaluated: In group 1 (n=11) the "old" tracer formulation was used for injection combined with the intraoperative use of the Tricam SL II + D-light C system (KARL STORZ Endoskope). In group 2 (n=13), an increased particle concentration of the hybrid tracer was injected with reduced volume. In group 3 (n=16) the fluorescence laparoscope was upgraded to an Image HUB 1 HD + D-light P system (KARL STORZ).

RESULTS Fluorescence-based SN identification increased from 64% in group 1 to 85% in group 2 and 93% in group 3 (p-value=0.004). On follow-up, there were fewer N0 patients with a R0 margin with biochemical recurrence (PSA>0.1 ng/mL) in group 3 (Fig. 1).

CONCLUSION By introducing a new tracer formulation and new fluorescence imaging hardware, intraoperative fluorescence SN detection improved significantly. This contributes to the refinement of the SN procedure, which in turn may improve regional staging in prostate cancer patients.

CLINICAL RELEVANCE/APPLICATION Improved intraoperative SN identification may lead to improved regional lymph node staging prostate cancer patients, resulting in better patient-tailored therapy planning and possibly improved survival.

SSQ12-09 Impact of 68Ga-PSMA PET/CT in Staging of Prostate Cancer Patients prior to Radiotherapy Frederik Lars Giesel MD, MBA (Presenter): Nothing to Disclose , Hanna Fiedler : Nothing to Disclose , Clemens Kratochwil MD : Nothing to Disclose , Ali Afshar-Oromieh : Nothing to Disclose , Uwe Haberkorn MD : Nothing to Disclose , Florian Sterzing MD : Nothing to Disclose , Juergen Debus MD, PhD : Nothing to Disclose PURPOSE

Prostate cancer risk stratification is based on PSA, T-stage and Gleason score and results in improved therapeutic decision-making. The purpose of this retrospective investigation is to evaluate the impact of 68Ga-PSMA PET as a novel pre-treatment staging method prior to radiotherapy.

METHOD AND MATERIALS 56 patients with prostate cancer were retrospectively analyzed with conventional CT and 68Ga-PSMA PET/CT imaging. 15 patients presented at diagnosis, while 41 patients presented with recurrence after total prostatectomy; 71% had high risk and 29% intermediate risk cancer according to the d'Amico criteria. .On conventional CT, lymph nodes were regarded as pathologically involved if their short axis diameter was ≥10mm. Lymph node involvement in 68Ga-PSMA PET was diagnosed when a node on CT demonstrated a maximum standardized uptake value (SUVmax) >2. TNM-classification was performed by two experienced readers in consensus.

RESULTS

26 of 56 (46.4%) patients was changed after 68Ga-PSMA PET imaging. This included 8 patients with changes at initial diagnosis and 18 patients at the time of recurrence. 13/26 patients (50%) with recurrence were changed from N0 to N1, 9 patients (34.6%) were changed from M0 to M1a, 4 patients (15.4%) were changed from M0 to M1b and 1 patient (3.8%) was changed from Tx to T2a. In 7/15 patients (46.6%) at initial diagnosis no metastases were detected in 68Ga-PSMA PET /CT. Among the 26 patients in whom 68Ga-PSMA PET upstaged their disease, all patients underwent modification of their therapy. Nodal upstaging resulted in individualized simultaneous integrated boost IMRT. With detection of distant metastases, patient management was changed from local radiotherapy to systemic therapy.

CONCLUSION These results suggest that 68Ga-PSMA PET/CT can more accurately stage patients with prostate cancer than conventional CT leading to changes in therapy. This agent could therefore, become important for more precise treatment of patients with primary or recurrent prostate cancer.

CLINICAL RELEVANCE/APPLICATION 68Ga-PSMA PET/CT can more accurately stage patients with prostate cancer than conventional imaging modalities resulting in changes of the treatment regime.

MIS-THA Molecular Imaging Thursday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Thu, Dec 4 12:15 PM - 12:45 PM Location: S503AB

Participants Moderator Ambros Johannes Beer MD : Nothing to Disclose Moderator Yasuhisa Fujibayashi PhD : Nothing to Disclose

Sub-Events MIS149 Efficient Labeling in Vitro with Non-Ionic-Gadolinium MRI Contrast Agent in Bone Marrow Stromal Cells of Neonatal Rats (Station #7) Yingqin Li (Presenter): Nothing to Disclose , Ying Tang : Nothing to Disclose , Rao Fu : Nothing to Disclose , Qiuhua Meng : Nothing to Disclose , Xue Zhou : Nothing to Disclose , Zemin Ling : Nothing to Disclose , Suwei Tian : Nothing to Disclose , Guojie Wang : Nothing to Disclose , Xueguo Liu MD : Nothing to Disclose , Lihua Zhou : Nothing to Disclose PURPOSE In order to explore a new and feasible molecular target, we using non-ionic-gadolinium (Gadodiamide, GE) in tracking of one bmarrow stromal cells (BMSCs) of neonatal rats and assessed its feasibility, safety and efficacy. Meanwhile, we investigated clinical MR signal characteristics of BMSCs labeling in vitro.

METHOD AND MATERIALS BMSCs were labeled by a rhodamine-conjugated fluorescent reagent (Fluorescent Arrest-In Transfection Reagent, Open biosystems, American) and Gadodiamide. Labeled BMSCs were taken scanning by a clinical 1.5 Tesla MR scanner (Phillips, USA) in vitro. Transfection efficiency were accessed by flow cytometric detection, fluorescence inversion microscopy and transmission electron microscopy (TEM). To evaluate the cellular characteristics of labeled BMSCs, we depicted the labeling cell growth curves, calculated cells survival ratio, analyzed cell viability and calculated cell proliferation.

RESULTS Flow cytometric analysis showed the positive labeling rate was 44.95% ± 2.42% (n=3). Under a fluorescence inversion microscope, transfection agent combined with Gd3+ were red within cytoplasm and around the blue-stained cell nucleus. The black and dense gadolinium particles were sporadic or confluent within phages in labeled cells under the TEM. There was no significant different in biological characteristics between the labeled and unlabeled BMSCs (P>0.05). In Vitro MR studies of labeling BMSCs showed the minimal number of detectable cells was 5×104. At 1, 3, 7, 14, 21, 28 days after transfection, signal enhanced on T1WI and SNR compared with the control groups.

CONCLUSION By applying clinical basic Gd-chelates and rhodamine-transfection agent to form Gd3+-basic plasmids, it would explore a new, effective, practical and rapid labeled protocol for BMSCs successfully. Those labeled targets could be detected by clinical conventional MR in vitro.

CLINICAL RELEVANCE/APPLICATION This work deals with the description of a cell transfection strategy based on the use of a commercially available Gadodiamide derivative for in vitro BMSCs detection by MRI.

MIS150 Turning T1- weighted Contrast on and off – An in Vitro MRI Study Using a New Molecule Switchable by Visible Light (Station #8) Catharina Gerda Klose (Presenter): Nothing to Disclose , Monika Huhndorf : Nothing to Disclose , Marcel Dommaschk : Nothing to Disclose , Christian Riedel : Nothing to Disclose , Olav Jansen MD, PhD : Nothing to Disclose , Rainer Herges : Nothing to Disclose PURPOSE

We investigated a new molecule that can change its magnetic properties from diamagnetic to paramagnetic and vice and versa by illuminating it with different wavelengths of visible light. The purpose was to find out if this magnetic switch can change T1 relaxivity in a way that it can be used as a switchable MRI contrast agent.

METHOD AND MATERIALS

We used a nickel complex as a molecular spin switch that can change between diamagnetic and paramagnetic state by exposing it with blue-green light (500 nanometers) and violet-blue light (435nm). The process leads to stable states and is fully reversible without fatigue. We designed a closed loop flow system attached to a light source and a pump outside our 3T MRI scanner (Achieva, Philips Medical Systems, Best , The Netherlands). The flow system also contained a reservoir enclosed in a head phantom inside the MRI Scanner. We repeatedly scanned the reservoir containing a solution of the molecule using T1 weighted sequences in order to evaluate the contrast dynamics. Outside the scanner the solution was permanently illuminated while being pumped through the flow system. This was repeated for different concentrations of the solution.

RESULTS

The T1w signal intensity in the reservoir increased significantly during the illumination with wavelengths of 500 nm as the molecules changed their magnetic state from diamagnetic to paramagnetic. In the same way, the T1w signal intensity decreased during illumination with a wavelength of 435 nm. While at high concentration (2.4 mmol) we found a signal-to-noise ratio (SNR) of 10.2, at lower concentration (0.9 mmol) the SNR dropped to 5.9. In addition, we could show that the molecules were much faster switched off than switched on. The half- life period was 2 min for switching off versus 8 min for switching on. The switching process was also concentration dependent. At a concentration of 0.9 mmol the half-life period for switching the contrast off was 2 minutes versus 7 minutes at a concentration of 2.4 mmol.

CONCLUSION

Our switchable molecule allows for generating noticeable T1w contrast differences within a period of time comparable to a standard MRI pulse sequence.

CLINICAL RELEVANCE/APPLICATION

Switchable contrast agent could be used to better delineate contrast enhancement by subtracting the tissue background because the molecule can be switched on and off as often as necessary.

MIS151 Molecular Imaging for the Diagnosis of Acute Ischemic Renal Injury in Rats by in situ Production of Ultrasound Detectable Microbubbles Using Nanoparticles (Station #9) Emilia Sue Olson MD, PhD (Presenter): Nothing to Disclose , Christopher Devin Malone MD : Nothing to Disclose , Inanc Ortac : Founder, DevaCell Inc , Sadik Esener : Nothing to Disclose , Robert Frederick Mattrey MD : Nothing to Disclose PURPOSE Purpose: Acute renal injury (ARI) is a leading cause of morbidity in ICUs worldwide. Hydrogen peroxide (H2O2), the most common reactive oxygen species is elevated in inflammatory and other conditions including ARI. CATalase loaded Synthetic Hollow Enzyme Loaded nanoSpheres (catSHELS) are nanoencapsulated molecules that catalyze H2O2 to water and oxygen, producing ultrasound detectable microbubbles. In this study we aimed to determine whether catSHELS can convert the H2O2 in acutely injured kidneys to allow their recognition on contrast specific ultrasound imaging.

METHOD AND MATERIALS ARI was produced in 4 pre-heparinized rats by completely occluding the left renal artery for 1 hour followed by 2 hours of reperfusion. After reperfusion, 10^12 particles of non-catalase containing SHELS were given IV. Thirty minutes later, animals were injected with 10^12 particles of catSHELs IV. Both the ARI and normal kidney were imaged immediately after injection and alternately for 10 minutes at 7MHz using the CPS mode of a Siemens Sequoia 512. In addition to subjective observation, video-intensity was measured of the entire kidney and background subtraction was performed. Urine samples were collected before renal artery occlusion and just prior to catSHELS injection.

RESULTS Echogenic enhancement was only observed in ARI kidneys when catSHELS were injected IV. Intensity of the injured kidneys post IV injection of control SHELS was 0.1±1.3, and increased to 5.0±0.9 post injection of catSHELS (p=0.001). Intensity of the non injured kidney was similar post injection of either control SHELS (-0.49±1.1) or catSHELS (-0.7 ± 2.6,, p=0.86). The difference between the injured and non injured kidneys post catSHEL injection was significant (p=0.02). Urine H2O2 levels increased from 19±8 �M at baseline to 59±24 �M immediately prior to injection of catSHELs.

CONCLUSION catSHELS allowed the recognition of acute renal injury by converting the H2O2 produced by the injury into ultrasound detectable microbubbles. Further efforts will involve dose optimization and ultimately translation to the clinic.

CLINICAL RELEVANCE/APPLICATION ARI is suspected when other conditions that cause decreased urine output are excluded. With the use of this novel ultrasound molecular imaging technique ARI can be diagnosed at the bedside. MIS152 A Two-Pool Modeling for 3 Tesla Magnetization Transfer MR Imaging of Prostate Cancer (Station #10) Ryan Nicholas Schurr (Presenter): Nothing to Disclose , Saba N. Elias MSc : Nothing to Disclose , Wenbo Wei : Nothing to Disclose , Jochen Keupp PhD : Employee, Koninklijke Philips NV , Michael Vinzenz Knopp MD, PhD : Nothing to Disclose , Guang Jia PhD : Nothing to Disclose , Steven Heymsfield : Nothing to Disclose PURPOSE

Multi-parametric magnetic resonance imaging (MRI) is used to aid in the diagnosis of prostate cancer. Magnetization transfer MRI (MT-MRI) may provide a complementary mechanism to reveal molecular-based contrast between the tumor and benign prostatic tissue. This study investigates the molecular mechanisms of MT-MRI of prostate cancer.

METHOD AND MATERIALS

Eighteen prostate cancer patients were imaged on a 3 Tesla MRI system (Philips, Best, Netherlands) before undergoing prostatectomy. A saturation pre-pulse was applied at frequencies ranging from -8 to 8 ppm with a power of 4 uT. Images were acquired using a single-slice, single-shot turbo spin echo sequence. From MT-spectral data, bound proton (associated with immobile macromolecules) and free proton (free water) pools were modeled as separate Lorentz functions using IDL. Parameters describing the full-width at half maximum (FWHM) and maximum magnitude of the bound and free proton components of the MT-spectra were obtained for the PZ, CG, and tumor regions of interest.

RESULTS The magnitude of the bound pool is 0.15 ± 0.05 for the PZ, 0.21 ± 0.03 for the CG, and 0.22 ± 0.05 for the tumor. This is significantly different between the PZ and the tumor, but not between the CG and the tumor (p=0.001 and p=0.12, respectively). The magnitude of the free pool is 0.77 ± 0.02 for the PZ, 0.76 ± 0.03 for the CG, and 0.75 ± 0.03 for the tumor. This is significantly different between the PZ and tumor, but not the CG and tumor (p=0.002 and p=0.142, respectively). The FWHM of the free pool is 7.4 ± 1.0 ppm for the PZ, 8.3 ± 0.6 ppm for the CG, and 8.2 ± 0.7 ppm for the tumor. This is significantly different between the PZ and CG, and the PZ and tumor (p=0.001 and p=0.0002, respectively).

CONCLUSION

Our data shows higher magnitude of the bound pool in the prostate cancer and CG regions, revealing greater concentration of immobile macromolecules, and a lower magnitude of the free pool in prostate cancer regions, indicating less free water in cancerous tissues than the PZ.

CLINICAL RELEVANCE/APPLICATION

Modeling the MT-spectra of the regions of the prostate provides immobile macromolecular and water information, useful for the application of MT-MRI as a unique and complementary method of improving contrast between tumor and benign prostate tissues.

MIE106 Surprise, Surprise: Incidental Findings on Routine PET-CT Examinations (Station #11) Vaiyapuri P. Sukumar MBBS (Presenter): Nothing to Disclose , Anver Kamil MBChB : Nothing to Disclose TEACHING POINTS The aim of the exhibit is: 1. To illustrate the prevelance of incidental findings on routine PET-CT examinations 2. To discuss the various incidental pathologies identified on routine PET-CT examinations 3. To discuss the relevance and significance of the incidental findings on routine PET-CT examinations.

TABLE OF CONTENTS/OUTLINE Review of imaging of incidental findings on routine PET-CT examinations illustrate Sample cases of various incidental findings Discussion of the incidental findings with regards to the prevelance and significance of the findings. Analysis of our data and the break down of the various incidental pathologies Conclusion

MIS-THB Molecular Imaging Thursday Poster Discussions

Scientific Posters MI AMA PRA Category 1 Credits ™: .50 Thu, Dec 4 12:45 PM - 1:15 PM Location: S503AB

Sub-Events High r1 Relaxivity Gadolinium-Containing Carbon Dots Nanoparticles as Contrast Agent for MRI MIS153 High r1 Relaxivity Gadolinium-Containing Carbon Dots Nanoparticles as Contrast Agent for MRI Angiography (Station #7) Shao Wu Wang MD : Nothing to Disclose , Song Chen : Nothing to Disclose , Mingqian Tan (Presenter): Nothing to Disclose PURPOSE

A new of high r1 relaxivity, water-soluble, gadolinium-containing carbon dots(Gd-CDots) nanoparticles with blue fluorescence as T 1WI contrast agents was used in MRI angiography.

METHOD AND MATERIALS The Gd-CDots nanoparticles were synthesized by Citric acid monohydrate and gadolinium chloride through a one-step heated hydrothermally at 200 °C for 8 h. The gadolinium with different concentrations were examined by a 3T MRI scanner using T1WI and T2WI, IR turbo spin echo sequence and multi-echo T2WI . R1 and R2 relaxivities were calculated by fitting signal changes in multi-IR T1WI and multi-TE T2WI using simple exponential equations. The rats were injection of the Gd-CDots and Gd-BOPTA into tail vein. Fat suppressed T 2WI were obtained to investigate the contrast changes in liver, kidney, muscle and aorta at the different time points.

RESULTS

The prepared Gd-CDots with different concentration of Gd has an r1 value of 14.5 mM-1s-1,17.3 mM-1s-1, 14.1 mM-1s-1, 33.4 mM-1s-1, r2 value of 18.0 mM-1s-1, 19.8 mM-1s-1, 15.9 mM-1s-1, 38.0 mM-1s-1 and r1/r2 ratio of 1.24, 1.13, 1.13, 1.14, which is competitive with commercial Gd-based contrast agent. Significant T1 contrast enhancement in the kidney and liver were evidenced in in vivo MRI after injection of Gd-CDots in rat through tail vein, similar to that observed in Gd-BOPTA enhanced MRI. The positive contrast enhancement is attributed to the small size and the reduced susceptibility of the nanoparticles, as well as the excellent colloidal stability in physiological environment. Firstly, the liver displayed significantly increased signal changes. Moreover, the kidney and bladder were observed increased signal changes, strongly suggesting renal excretion of the Gd-CDots nanoparticles. Gd-CDots has a much longer blood retention time than small molecule Gd for prolonged imaging time for organs of interest, providing a potential long half time T1WI contrast agents for imaging of vascular of disease tissues.

CONCLUSION Gd-CDots has a much longer blood retention time than small molecule Gd for prolonged imaging time for organs of interest, providing a potential long half time T1WI contrast agents for MRI Angiography. CLINICAL RELEVANCE/APPLICATION

The Gd-containing nanoparticles exhibit excellent T1 contrast in vivo MRI studies, especially for kidney and liver, providing a potential long half contract agent for MRI Angiography.

MIS154 Recruitment of CCL2-dependent Macrophage Decreases Response to Antiangiogenic Treatment: Preliminary Study Using Dynamic Susceptibility Contrast Perfusion MR Imaging and Microvessel Density Measurement in a Rat Glioblastoma Model (Station #8) Seung Hong Choi MD, PhD (Presenter): Nothing to Disclose PURPOSE

Tumor-associated macrophages (TAMs) have long been considered capable of destroying tumor cells and presenting tumor antigens to effector T cells to trigger antitumor responses. Recently, several studies have shown that TAM recruitment to the cancer site increases tumor angiogenesis as well as tumor cell migration, invasion and dissemination and that TAMs also suppress the immune response that targets tumor cells. Dynamic susceptibility contrast (DSC) MR imaging is advanced technique that provides cerebral blood volume (CBV) and can be used for the assessment of tumor response to therapy, especially for antiangiogenic therapy such as bevacizumab. The purpose of the present study is to investigate whether the recruitment of CCL2-dependent macrophage decreases response to antiangiogenic treatment by using DSC perfusion MR Imaging and microvessel density (MVD) measurement in a rat glioblastoma model.

METHOD AND MATERIALS

We established U87 human glioblastoma cell line expressing macrophage chemoattractant CCL2, and confirmed the CCL2 expression by western blot and cytokine assay. For in vivo study, athymic nude rats were used for orthotopic brain tumor model (control (n = 6), and CCL2 group (n = 6), respectively). And then 2 weeks after transplantation, DSC MR imaging was performed with 9.4T animal MR scanner for pre-treatment MR imaging. Bevacizumab (20 mg/kg) was intra-peritoneally injected twice a week, then post-treatment MR imaging was performed. After sacrifice of the rats, MVD was determined by CD34, and macrophages were stained with CD68.

RESULTS CCL2 expressing tumors showed significantly higher relative CBV than mock-transfected controls after treatment of bevacizumab (3.5 ± 1.2 vs 1.3 ± 0.4, P ≤ 0.05). In histology analysis, more MVD formatted by bevacizumab resistance and more macrophages recruited by CCL2 cytokine were observed in CCL2 expressing tumor than mock-transfected control tumors after treatment of bevacizumab.

CONCLUSION We believe that CCL2 expression of glioblastoma can induce the antiangiogenic drug resistance by recruitment We believe that CCL2 expression of glioblastoma can induce the antiangiogenic drug resistance by recruitment of macrophages, which can be assessed noninvasively with DSC MR imaging.

CLINICAL RELEVANCE/APPLICATION DSC imaging can be used for the noninvasive evaluation of the resistance to antiangiogenic treatment in the preclinical study.

MIS155 Enzyme Inhibitors Impressively Enhance Tumor Uptake of Radiopeptides (Station #9) Marion De Jong PhD (Presenter): Nothing to Disclose , Theodosia Maina : Nothing to Disclose , Berthold Nock : Nothing to Disclose PURPOSE Radiopeptide drugs like radiolabeled octreotide-analogs are successfully being applied for tumor visualization and treatment. However, translation of this paradigm to other radiopeptide ligands has been severely hampered by their often-poor metabolic stability. We hypothesized a novel application -single co-injection of a specific enzyme inhibitor- to improve peptide bioavailability and hence tumor uptake in vivo.

METHOD AND MATERIALS The neutral endopeptidase inhibitor phosphoramidon (PA, 0.3mg) was injected with 111In-labeled somatostatin, gastrin and bombesin radiopeptides in different mouse models (healthy mice as well as tumor-bearing SCID and nude mice). PA is a potent (IC50 34 nM) and reversible competitive NEP-inhibitor. 4 and 24 h post injection, biodistribution as well as dynamic and static animal SPECT/CT imaging was performed.

RESULTS We could provoke a remarkable and very significant rise (up to 40 times the control values) in the percentage of circulating intact 111In-labeled somatostatin, gastrin and bombesin radiopeptides in healthy mice after PA coinjection. Most importantly, this strategy resulted in a spectacular increase of radiolabel accumulation (up to 14 times the control values) in the different types of tumors xenografted in the mice. The improved tumor uptake could be clearly visualized by SPECT/CT as well.

CONCLUSION Our findings open exciting new opportunities for the application of biodegradable peptide-drugs of either natural or synthetic origin as well as for the rationale design of in vivo stable analogs. They also provide a versatile tool for elucidating enzyme - peptide interactions.

CLINICAL RELEVANCE/APPLICATION not applicable yet

MIS156 SPECT/CT —A Valuable Adjunct to Bone Scintigraphy [ MI Scavenger Hunt! ] (Station #10) Olga Kagna MD : Nothing to Disclose , Natalia Puchkov : Nothing to Disclose , Natalia Pirmisashvili : Nothing to Disclose , Daniela Militianu MD : Nothing to Disclose , Gad Abikhzer MD (Presenter): Nothing to Disclose , Ora Israel MD : Consultant, General Electric Company PURPOSE

Bone scintigraphy (BS) is the most frequently performed general nuclear medicine procedure. Present study assesses referral patterns to bone SPECT/CT as well as its frequency and type of incremental value to functional assessment of the skeleton.

METHOD AND MATERIALS

Bone SPECT/16-CT (Discovery 670, GE Healthcare) was performed after administration of 925 MBq 99mTc-MDP and after completion of the planar BS. Studies performed over a 20 months period in 135 patients (80 M,55 F, age 7-85) were retrieved and retrospectively reviewed for referral criteria and the presence of any incremental value (defined as lesion localization and characterization). Indications for BS included skeletal pain (n=71), fracture or infection (n=30), metastatic survey (n=25), inconclusive prior imaging tests (n=9). The decision for performing SPECT/CT was based on findings on planar BS, on known clinical complaints and/or on results of prior imaging test.

RESULTS

Four groups of referral criteria to SPECT/CT were found. A. unclear localization of lesions to bone or soft tissue (ST) - 19 pts (14%). SPECT/CT correctly localized all sites (10 bone,5 ST, 4 bone+ST) and had an added value in 17/19 cases (89%) characterizing 15 and guiding further tests in 2 lesions. B. unclear localization of lesions to specific parts of bone - 59 pts (44%). SPECT/CT correctly localized all foci and characterized 55/59 (93%). C. diagnosis of bone lesion -52 pts (38%). SPECT/CT had an added value in 47/52 lesions (90%) defining 37 and guiding further tests in 10. D. diagnosis of ST lesions - 5 pts (4%). SPECT/CT had an added value in all cases (100%),defining 3 and guiding further tests in 2 sites. Overall SPECT/CT correctly localized all sites of skeletal and ST uptake and improved the diagnostic accuracy of BS with precise characterization of lesions in 110/135 pts (81%) and guiding further tests in 14/135 pts (10%).

CONCLUSION

The use of bone SPECT/CT was associated with an incremental improvement in the diagnostic capabilities and clinical impact of BS. Bone SPECT/CT was of value in all cases with unclear lesion localization. Furthermore it provided additional information for precise characterization of abnormal tracer uptake in the majority (91%) of patients.

CLINICAL RELEVANCE/APPLICATION SPECT/CT is of value for improving the diagnostic accuracy and clinical impact as an adjunct to bone scintigraphy