DOCSLIB.ORG

A Technique for Standardized Central Analysis of 6-18F-Fluoro-L-DOPA PET Data from a Multicenter Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Technique for Standardized Central Analysis of 6-18F-Fluoro-L-DOPA PET Data from a Multicenter Study A Technique for Standardized Central Analysis of 6-18F-Fluoro-L-DOPA PET Data from a Multicenter Study Alan L. Whone, MRCP1; Dale L. Bailey, PhD2; Philippe Remy, PhD3; Nicola Pavese, MD1; and David J. Brooks, DSc1 1Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom; 2Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, Australia; and 3CEA-Centre National de la Recherche Scientifique Unite´ de Recherche Associe´e 2210, Service Hospitalier Frederic Joliot, Orsay, France tralized analysis offers the potential for improved detection of We have recently completed a large 6-18F-fluoro-L-DOPA (18F- outcomes due to the standardization of the analytic approach DOPA) PET study comparing rates of loss of dopamine terminal and allows the analysis of large numbers of PET studies. function in Parkinson’s disease (PD) patients taking either the Key Words: PET; 18F-DOPA; Parkinson’s disease; progression; dopamine agonist ropinirole or L-DOPA. This trial involved a central analysis “distributed acquisition/centralized analysis” method, in which J Nucl Med 2004; 45:1135–1145 18F-DOPA images were acquired at 6 different PET centers around the world and then analyzed at a single site. To our knowledge, this is the first time such a centralized approach has been employed with 18F-DOPA PET and this descriptive basic science article outlines the methods used. Methods: One hun- With rapid advances in molecular medicine, the pro- dred eighty-six PD patients were randomized (1:1) to ropinirole duction of neuroprotective or neurorestorative agents that or L-DOPA therapy, and 18F-DOPA PET was performed at base- affect the progression of degenerative conditions such as line and again at 2 y. The primary outcome measure was the Parkinson’s disease (PD) is becoming a realizable ambition percentage change in putamen 18F-DOPA influx rate constant for academic institutions and pharmaceutical companies. (Ki) from Patlak graphical analysis. Dynamic images were ac- quired and reconstructed using each center’s individual proto- That said, although the safety and tolerability of novel cols before being transferred to the site performing the central agents can often be confirmed in a straightforward manner, analysis. Once there, individual parametric Ki images were cre- demonstrating therapeutic efficacy is frequently more com- ated using a single analysis program without file formats being plex (1,2). The gold standard for assessing in vivo drug transformed from the original. Parametric images were then benefit is the analysis of clinical outcome measures after normalized to standard space and K values extracted with a i double-blind randomized controlled clinical trials. How- region of interest analysis. Significant Ki changes were also localized at a voxel level with statistical parametric mapping. ever, assessing disease-modifying therapies in PD by clin- These processes required numerous checks to ensure the in- ical outcome measures alone may be problematic (1,2). tegrity of each dataset. Results: Three hundred twenty-five (170 Hence, besides the need for the development of neuropro- baseline, 155 follow-up) dynamic PET datasets were acquired, tective treatments in PD, there is a requirement for the of which 12 were considered uninterpretable due to missing development of adjunctive objective measures by which time frames, radiopharmaceutical problems, lack of measured therapeutic efficacy can be assessed. In this regard, 6-18F- attenuation correction, or excessive head movement. In those 18 datasets suitable for central analysis, after quality control and fluoro-L-DOPA ( F-DOPA) PET has been shown to pro- spatial normalization of the images had been applied, putamen vide an objective biomarker of PD progression, where the 18F-DOPA signal decline was found to be significantly (one third) fall in striatal 18F-DOPA PET uptake over time reflects the slower in the ropinirole group compared with that of the L-DOPA degeneration of dopamine terminals (3–5). group. Conclusion: Paired 18F-DOPA-PET images acquired We have recently completed a randomized controlled from multiple sites can be successfully analyzed centrally to clinical trial assessing, in early PD, the potential disease- assess the efficacy of potential disease-modifying therapies in PD. However, numerous options must be considered and data modifying effects of ropinirole, a dopamine agonist, com- 18 checks put in place before adopting such an approach. Cen- pared against L-DOPA treatment where changes in F- DOPA PET signal rather than clinical endpoints were the primary outcome measure and where statistically significant Received Sep. 8, 2003; revision accepted Jan. 14, 2004. differences in 18F-DOPA uptake loss were found (6). This For correspondence or reprints contact: Alan L. Whone, MRCP, Cyclotron Building, Hammersmith Hospital, Du Cane Rd., London, W12 0NN, U.K. investigation obtained effect sizes similar to 2 previous E-mail: [email protected] 18F-DOPA studies investigating dopamine agonists in PD CENTRALIZED ANALYSIS OF 18F-DOPA PET • Whone et al. 1135 (7,8) but involved group sizes far larger than reported pre- constant (Ki), which measures the rate of accumulation of the viously (enrolled population ϭ 186). To study such a large radiotracer. population at a single PET site would be a considerable One hundred eighty-six patients with a clinical diagnosis of PD Յ undertaking and have major implications in terms of patient and symptom duration of 2 y were assigned (1:1) to ropinirole or 18 recruitment and retention. Thus, a “distributed acquisition/ L-DOPA therapy by the sponsor. F-DOPA PET was performed centralized analysis” model was used, in which data were between 4 wk and 3 mo after drug initiation and again at 2 y (within 4 wk of the 24-mo clinical assessment). The primary acquired at 6 different PET centers around the world and outcome measure was the mean percentage reduction in the side- then analyzed in a standardized manner at a single site. The 18 to-side averaged putamen F-DOPA influx constant (Ki) between clinical and imaging results of this study have been reported pairs of baseline and follow-up scans. 18F-DOPA PET imaging elsewhere (6); therefore, the purpose of this descriptive was performed at 6 centers in Europe and North America (Table 1) methodologic paper is to provide further details of our with all dynamic image sequences forwarded to our center for method of centralized PET analysis. To our knowledge, this analysis. As the purpose of this article is to describe how we is the first study of PD progression to utilize a centralized performed this distributed acquisition/centralized analysis, details analysis technique, and this article outlines the methodology of power calculations, patient selection criteria, blinding, random- used to organize, implement quality control, and standardize ization, clinical assessment, drug dosing, baseline demographics, such a large volume of image datasets (170 baseline scans, and patient withdrawal are not reported here but can be found in 155 follow-up scans) emanating from different PET centers. the article describing the primary study outcomes (6). It is hoped this will serve as a guide for similar studies in the PET Cameras future. The 6 PET cameras used are shown in Table 1. Siemens/CTI manufactured all of the cameras; however, a variety of models MATERIALS AND METHODS were used. It was recognized that investigating a combination of Study Design and Subjects images from different tomographs, each with different resolution We used a standard method for assessing 18F-DOPA uptake, in and sensitivity, could introduce bias. However, the study protocol which it is assumed there is monodirectional uptake from the blood stipulated baseline and follow-up scans be acquired with the same into the basal ganglia, via the exchangeable pool, after injection of camera and the outcome measure was the percentage (rather than the radiotracer. The Patlak graphical analysis technique (9,10) absolute) change in putamen Ki between scan pairs. It was also applied to such a system allows the derivation of an influx rate acknowledged there was a risk of bias if more patients from one TABLE 1 Details of PET Centers, Scanners Used, Acquisition Protocol, and Subject Numbers Reported in-plane spatial resolution FWHM Acquisition protocol PET center Scanner model (mm) Reference (frame sequence) No. of subjects in study* United Kingdom ECAT HRϩϩ 4.5 11 26 frames; higher frame frequency 34 baseline scans: 16 r, 18 l Hammersmith acquisition initially, 95-min Outcome population: 12 r, 12 l duration France ECAT HRϩ 4.6 12 9 frames; frame frequency 39 baseline scans: 19 r, 20 l Orsay acquisition constant throughout, Outcome population: 17 r, 16 l 90-min duration United States ECAT EXACT47 6.0 13 29 frames; higher frame frequency 39 baseline scans: 19 r, 18 l Atlanta acquisition initially, 120-min Outcome population: 15 r, 11 l duration Germany ECAT EXACT47 6.0 13 9 frames; frame frequency 25 baseline scans: 15 r, 10 l Ulm acquisition constant throughout, Outcome population: 10 r, 6 l 90-min duration Canada ECAT 953B 4.8 14 25 frames; higher frame frequency 20 baseline scans; 11 r, 9 l UBC acquisition initially, 95-min Outcome population: 10 r, 7 l duration Canada ECAT ART 6.2 15 58 frames; frame frequency 15 baseline scans; 5 r, 10 l McMaster acquisition constant throughout, Outcome population: 4 r, 7 l 150-min duration *Subjects undergoing baseline scans at each center and subjects from each center in primary outcome population (after patient withdrawals). FWHM ϭ full width at half maximum; r ϭ ropinirole; l ϭ L-DOPA; UBC ϭ University of British Columbia. Data format versions used for each scanner were CTI proprietary formats, either ECAT6 or ECAT7. 1136 THE JOURNAL OF NUCLEAR MEDICINE • Vol. 45 • No. 7 • July 2004 treatment group underwent imaging with lower resolution tomo- File Formats and Data Transfer graphs compared with the other.
Load more

Recommended publications
  • PET Imaging of Occult Tumours by Temporal Integration of Tumour-Acidosis Signals from Ph-Sensitive 64Cu-Labelled Polymers
    ARTICLES https://doi.org/10.1038/s41551-019-0416-1 PET imaging of occult tumours by temporal integration of tumour-acidosis signals from pH-sensitive 64Cu-labelled polymers Gang Huang 1, Tian Zhao1, Chensu Wang 1, Kien Nham2, Yahong Xiong2, Xiaofei Gao3, Yihui Wang3, Guiyang Hao 2, Woo-Ping Ge3, Xiankai Sun2, Baran D. Sumer 4* and Jinming Gao 1,4* Owing to the diversity of cancer types and the spatiotemporal heterogeneity of tumour signals, high-resolution imaging of occult malignancy is challenging. 18F-fluorodeoxyglucose positron emission tomography allows for near-universal cancer detec- tion, yet in many clinical scenarios it is hampered by false positives. Here, we report a method for the amplification of imaging contrast in tumours via the temporal integration of the imaging signals triggered by tumour acidosis. This method exploits the catastrophic disassembly, at the acidic pH of the tumour milieu, of pH-sensitive positron-emitting neutral copolymer micelles into polycationic polymers, which are then internalized and retained by the cancer cells. Positron emission tomography imaging of the 64Cu-labelled polymers detected small occult tumours (10–20 mm3) in the brain, head, neck and breast of mice at much higher contrast than 18F-fluorodeoxyglucose, 11C-methionine and pH-insensitive 64Cu-labelled nanoparticles. We also show that the pH-sensitive probes reduce false positive detection rates in a mouse model of non-cancerous lipopolysaccharide-induced inflammation. This macromolecular strategy for integrating tumour acidosis should enable improved cancer detection, surveil- lance and staging. ancer exhibits diverse genetic and histological differences tumours over the surrounding normal tissues often leads to false from normal tissues1.
    [Show full text]
  • [123I]FP-CIT SPECT in Atypical Degenerative Parkinsonism
    CONTRAST AGENT EVALUATION [123I]FP-CIT SPECT in atypical degenerative parkinsonism One of the most widely used techniques to support the clinical diagnosis of Parkinson’s disease is the SPECT scan with [123I]FP-CIT. This tracer binds reversibly and visualizes the striatal presynaptic dopamine transporters. Several uncertainties remain on the value of [123I]FP-CIT and SPECT in atypical degenerative parkinsonian syndromes. In this concise review, we discuss the contribution of SPECT and [123I]FP-CIT in supporting the clinical diagnosis of Parkinson’s disease and their role in the differential diagnosis of Parkinson’s disease and atypical degenerative parkinsonism. The chemistry, pharmacodynamics and pharmacokinetics of [123I]FP-CIT are also discussed. 1,2,3 KEywordS: atypical degenerative parkinsonism n FP-CIT n ioflupane n SPECT Ioannis U Isaias* , Giorgio Marotta4, Gianni Pezzoli2, Parkinson’s disease (PD) is the second most dystonic tremor [15] and psychogenic parkin- Osama Sabri5 [1] [16,17] 5,6 common neurodegenerative disorder , yet sonism . In this concise review, we will & Swen Hesse 123 early accurate diagnosis remains challenging. discuss the role of SPECT and [ I]FP-CIT in 1Università degli Studi di Milano, The estimated prevalence of PD is 0.5–1% in supporting the clinical diagnosis of PD and its Dipartimento di Fisiologia Umana, those aged 65–69 years and 1–3% in those aged differential diagnosis with ADP. Milano, Italy 2Centro per la Malattia di Parkinson e i ≥80 years [1]. Although the clinical diagnosis of Disturbi del Movimento,
    [Show full text]
  • DICOM Conformance Template
    g GE Heathcare Technical Publications Direction 5507068-1EN (DOC1584283) Revision 1 DaTQUANT Application™ DICOM CONFORMANCE STATEMENT Copyright 2015 by General Electric Co. Do not duplicate g GE Heathcare LIST OF REVISIONS REV DATE DESCRIPTION PAGES APPR. 1 May 2015 Initial Release All M. Mesh DATQUANT APPLICATION GE Healthcare DICOM CONFORMANCE STATEMENT DIR 5507068-1EN (DOC1584283) REV 1 THIS PAGE LEFT INTENTIONALLY BLANK DATQUANT APPLICATION GE Healthcare DICOM CONFORMANCE STATEMENT DIR 5507068-1EN (DOC1584283) REV 1 CONFORMANCE STATEMENT OVERVIEW DaTQUANT application is an application that uses NM and CT images and creates NM, SC and MFSC images. Table 0.1 provides an overview of the network services supported by the DaTQUANT application. Table 0.1 – APPLICATION SOP Classes User of Object Creator of Instances Object Instances Transfer Secondary Capture Image Storage No Yes Multi-frame True Color Secondary Capture Image Storage No Yes Nuclear Medicine Image Storage Yes Yes Computerized Tomography Image Storage Yes No 4 DATQUANT APPLICATION GE Healthcare DICOM CONFORMANCE STATEMENT DIR 5507068-1EN (DOC1584283) REV 1 1. INTRODUCTION ............................................................................................................... 8 1.1 Overview ..................................................................................................................................................................... 8 1.2 Overall DICOM Conformance Statement Document Structure ..........................................................................
    [Show full text]
  • Brain Imaging
    Publications · Brochures Brain Imaging A Technologist’s Guide Produced with the kind Support of Editors Fragoso Costa, Pedro (Oldenburg) Santos, Andrea (Lisbon) Vidovič, Borut (Munich) Contributors Arbizu Lostao, Javier Pagani, Marco Barthel, Henryk Payoux, Pierre Boehm, Torsten Pepe, Giovanna Calapaquí-Terán, Adriana Peștean, Claudiu Delgado-Bolton, Roberto Sabri, Osama Garibotto, Valentina Sočan, Aljaž Grmek, Marko Sousa, Eva Hackett, Elizabeth Testanera, Giorgio Hoffmann, Karl Titus Tiepolt, Solveig Law, Ian van de Giessen, Elsmarieke Lucena, Filipa Vaz, Tânia Morbelli, Silvia Werner, Peter Contents Foreword 4 Introduction 5 Andrea Santos, Pedro Fragoso Costa Chapter 1 Anatomy, Physiology and Pathology 6 Elsmarieke van de Giessen, Silvia Morbelli and Pierre Payoux Chapter 2 Tracers for Brain Imaging 12 Aljaz Socan Chapter 3 SPECT and SPECT/CT in Oncological Brain Imaging (*) 26 Elizabeth C. Hackett Chapter 4 Imaging in Oncological Brain Diseases: PET/CT 33 EANM Giorgio Testanera and Giovanna Pepe Chapter 5 Imaging in Neurological and Vascular Brain Diseases (SPECT and SPECT/CT) 54 Filipa Lucena, Eva Sousa and Tânia F. Vaz Chapter 6 Imaging in Neurological and Vascular Brain Diseases (PET/CT) 72 Ian Law, Valentina Garibotto and Marco Pagani Chapter 7 PET/CT in Radiotherapy Planning of Brain Tumours 92 Roberto Delgado-Bolton, Adriana K. Calapaquí-Terán and Javier Arbizu Chapter 8 PET/MRI for Brain Imaging 100 Peter Werner, Torsten Boehm, Solveig Tiepolt, Henryk Barthel, Karl T. Hoffmann and Osama Sabri Chapter 9 Brain Death 110 Marko Grmek Chapter 10 Health Care in Patients with Neurological Disorders 116 Claudiu Peștean Imprint 126 n accordance with the Austrian Eco-Label for printed matters.
    [Show full text]
  • Lettirs to Th Editor Radiation Injury from Interstitial Injection Of
    DEPARTMENTS Lettirs to th Editor Radiation Injury from Interstitial Injection of measuring approximately 2 cm x 1 cm. Monitoring of the site Iodine-131-Iodocholesterol demonstrated retention of 131!(Fig. 2). On the basis of serial counts, the half-time was 5.5 days at the i.v. injection site. TO THE EDITOR: A 44-yr-oldman wasinvestigatedfor recur The absorbeddose deliveredto the overlyingskin cannot be rent Cushing's disease. An adrenal gland scan was initiated with precisely calculated because it has a very strong inverse depend injection of 34-MBq of ‘31I-iodocholesterol over a 5-mm interval. ence on the interstitial volume occupied by the injectate, and this Prior to injection, blood was withdrawn into the hub of the volume is not accurately known. The absorbed dose can be syringe to ensure correct i.v. placement. At the conclusion of the estimated by treating the interstitial volume occupied by the injection, the patient volunteered that the injection had been the injectate as a disk of the same area as the erythematous patch; least painful i.v. entry he had experienced. Seven days later, the thickness of this volume can be roughly estimated. The imaging failed to detect any radioactivity in the field of view volumeofdistributionwasassumedto remainconstantovertime centered on the adrenal glands. Monitoring of the injection site since the injectate is not water-soluble. The absorbed dose in this demonstrated essentially complete retention of the radiophar volume can be calculated by the method of Johns and Cun maceutical at the site. ningham (1). Because the model assumes no activity outside the The patient returned 13 days later (i.e., 20 days after the volume,the absorbeddose in the regionadjacentto this volume injection) to inquire about the tender pruritic and erythematous within the range of the beta particles (i.e., the skin) can be patch at the injection site at which time the photograph in Figure estimated to be halfthe dose inside the volume.
    [Show full text]
  • Nuclear Pharmacy Quick Sample
    12614-01_CH01-rev3.qxd 10/25/11 10:56 AM Page 1 CHAPTER 1 Radioisotopes Distribution for Not 1 12614-01_CH01-rev3.qxd 10/25/1110:56AMPage2 2 N TABLE 1-1 Radiopharmaceuticals Used in Nuclear Medicine UCLEAR Chemical Form and Typical Dosage P Distribution a b HARMACY Radionuclide Dosage Form Use (Adult ) Route Carbon C 11 Carbon monoxide Cardiac: Blood volume measurement 60–100 mCi Inhalation Carbon C 11 Flumazenil injection Brain: Benzodiazepine receptor imaging 20–30 mCi IV Q UICK Carbon C 11 Methionine injection Neoplastic disease evaluation in brain 10–20 mCi IV R Carbon C 11 forRaclopride injection Brain: Dopamine D2 receptor imaging 10–15 mCi IV EFERENCE Carbon C 11 Sodium acetate injection Cardiac: Marker of oxidative metabolism 12–40 mCi IV Carbon C 14 Urea Diagnosis of Helicobacter pylori infection 1 µCi PO Chromium Cr 51 Sodium chromate injection Labeling red blood cells (RBCs) for mea- 10–80 µCi IV suring RBC volume, survival, and splenic sequestration Cobalt Co 57 Cyanocobalamin capsules Diagnosis of pernicious anemia and 0.5 µCi PO Not defects of intestinal absorption Fluorine F 18 Fludeoxyglucose injection Glucose utilization in brain, cardiac, and 10–15 mCi IV neoplastic disease Fluorine F 18 Fluorodopa injection Dopamine neuronal decarboxylase activity 4–6 mCi IV in brain Fluorine F 18 Sodium fluoride injection Bone imaging 10 mCi IV Gallium Ga 67 Gallium citrate injection Hodgkin’s disease, lymphoma 8–10 mCi IV Acute inflammatory lesions 5 mCi IV Indium In 111 Capromab pendetide Metastatic imaging in patients with biopsy-
    [Show full text]
  • Pharmaceuticals Appendix
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ADAPALENE 106685-40-9 ABANOQUIL 90402-40-7 ADAPROLOL 101479-70-3 ABECARNIL 111841-85-1 ADEMETIONINE 17176-17-9 ABLUKAST 96566-25-5 ADENOSINE PHOSPHATE 61-19-8 ABUNIDAZOLE 91017-58-2 ADIBENDAN 100510-33-6 ACADESINE 2627-69-2 ADICILLIN 525-94-0 ACAMPROSATE 77337-76-9 ADIMOLOL 78459-19-5 ACAPRAZINE 55485-20-6 ADINAZOLAM 37115-32-5 ACARBOSE 56180-94-0 ADIPHENINE 64-95-9 ACEBROCHOL 514-50-1 ADIPIODONE 606-17-7 ACEBURIC ACID 26976-72-7 ADITEREN 56066-19-4 ACEBUTOLOL 37517-30-9 ADITOPRIME 56066-63-8 ACECAINIDE 32795-44-1 ADOSOPINE 88124-26-9 ACECARBROMAL 77-66-7 ADOZELESIN 110314-48-2 ACECLIDINE 827-61-2 ADRAFINIL 63547-13-7 ACECLOFENAC 89796-99-6 ADRENALONE 99-45-6 ACEDAPSONE 77-46-3 AFALANINE 2901-75-9 ACEDIASULFONE SODIUM 127-60-6 AFLOQUALONE 56287-74-2 ACEDOBEN 556-08-1 AFUROLOL 65776-67-2 ACEFLURANOL 80595-73-9 AGANODINE 86696-87-9 ACEFURTIAMINE 10072-48-7 AKLOMIDE 3011-89-0 ACEFYLLINE CLOFIBROL 70788-27-1
    [Show full text]
  • Qualification Opinion on Dopamine Transporter Imaging As an Enrichment Biomarker for Parkinson’S Disease Clinical Trials in Patients with Early Parkinsonian Symptoms
    29 May 2018 EMA/CHMP/SAWP/765041/2017 Committee for Medicinal Products for Human Use (CHMP) Qualification opinion on dopamine transporter imaging as an enrichment biomarker for Parkinson’s disease clinical trials in patients with early Parkinsonian symptoms Draft agreed by Scientific Advice Working Party 26 October 2017 Adopted by CHMP for release for consultation 09 November 20171 Start of public consultation 24 January 20182 End of consultation (deadline for comments) 07 March 20183 Adoption by CHMP 26 April 2018 Biomarker, Molecular neuroimaging, Parkinson’s disease Keywords 1 Last day of relevant Committee meeting. 2 Date of publication on the EMA public website. 3 Last day of the month concerned. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Executive summary Critical Path Global Ltd.’s Critical Path for Parkinson’s (CPP) is a multinational consortium of the Critical Path Institute supported by Parkinson’s UK and industry. This broad collaboration of pharmaceutical companies, government agencies, academic institutions, and charities aims to accelerate the development of therapies for Parkinson’s disease (PD). The CPP Imaging Biomarker team aims to achieve a qualification opinion by EMA Committee for Medical Products for Human Use (CHMP) for the use of low baseline Dopamine Transporter levels for subject enrichment in clinical trials in early stages of PD. This package reports the results of the Critical Path Global Ltd.
    [Show full text]
  • Slides Report on Recent Factors Related to the T&E Report, and Are Not That of the Convened Subcommittee
    Overview: 2019-2020 ACMUI Activities Darlene Metter, M.D. ACMUI Chair/Diagnostic Radiologist November 18, 2020 Today’s Agenda • A. Robert Schleipman, Ph.D. (ACMUI Vice-Chair) – ACMUI’s Comments on the Staff’s Evaluation of Training and Experience for Radiopharmaceuticals Requiring a Written Directive • Ms. Melissa Martin (ACMUI Nuclear Medicine Physicist) – ACMUI’s Comments on Extravasations 2 Today’s Agenda cont’d • Mr. Michael Sheetz (ACMUI Radiation Safety Officer) – ACMUI’s Comments on Patient Intervention and Other Actions Exclusive of Medical Events • Hossein Jadvar, M.D., Ph.D. (ACMUI Nuclear Medicine Physician) – Trending Radiopharmaceuticals 3 Overview of the ACMUI • ACMUI Role • Membership • 2019-2020 Topics • Current Subcommittees • Future 4 Role of the ACMUI • Advise the U.S. Nuclear Regulatory Commission (NRC) staff on policy & technical issues that arise in the regulation of the medical use of radioactive material in diagnosis & therapy. • Comment on changes to NRC regulations & guidance. • Evaluate certain non-routine uses of radioactive material. 5 Role of the ACMUI (cont’d) • Provide technical assistance in licensing, inspection & enforcement cases. • Bring key issues to the attention of the Commission for appropriate action. 6 ACMUI Membership (12 members) • Healthcare Administrator (Dr. Arthur Schleipman) • Nuclear Medicine Physician (Dr. Hossein Jadvar) • 2 Radiation Oncologists (Drs. Ronald Ennis & Harvey Wolkov) • Nuclear Cardiologist (Dr. Vasken Dilsizian) • Diagnostic Radiologist (Dr. Darlene Metter) • Nuclear Pharmacist (Mr. Richard Green) 7 7 ACMUI Membership (12 members) • 2 Medical Physicists Nuclear Medicine (Ms. Melissa Martin) Radiation Therapy (Mr. Zoubir Ouhib) • Radiation Safety Officer (Mr. Michael Sheetz) • Patients’ Rights Advocate (Mr. Gary Bloom*) • FDA Representative (Dr. Michael O’Hara) • Agreement State Representative (Ms.
    [Show full text]
  • Evidence-Based Indications for the Use of PET-CT in the UK 2016
    Evidence-based indications for the use of PET-CT in the United Kingdom 2016 _________________________________ The Royal College of Radiologists, Royal College of Physicians of London, Royal College of Physicians and Surgeons of Glasgow, Royal College of Physicians of Edinburgh, British Nuclear Medicine Society, Administration of Radioactive Substances Advisory Committee Contents Foreword 1 Non-FDG tracers for clinical practice 10 Indications for non-FDG tracers 10 Indications for 18F-fluorodeoxyglucose (FDG) PET-CT 3 Key references 13 Oncology applications 3 Indications for FDG scans 13 Non-oncological applications 8 Indications for non-FDG scans 25 1 www.rcr.ac.uk Foreword Since its introduction into clinical practice in the UK 26 years ago, positron emission tomography (PET) followed by positron emission tomography-computed tomography (PET-CT) has become a key investigative tool in the assessment of cancer and non-cancer medical conditions. The Inter-Collegiate Standing Committee on Nuclear Medicine (ICSCNM) supported the development of PET-CT in the UK through a number of initiatives including the 2003 document Positron emission tomography – A strategy for provision in the UK, the forerunner of the publication PET-CT in the UK. A strategy for development and integration of a leading edge technology within routine clinical practice in the UK. The publication of the first version of Evidence-based indications for the use of PET-CT in the United Kingdom 2012 was a landmark ICSCNM document. Authored by Sally Barrington and Andrew Scarsbrook, it provided, for the first time, a guide to the use of PET-CT in clinical practice and the evidence-base on which this was founded.
    [Show full text]
  • Fluorodopa F-18 [18F]FDOPA
    Fluorodopa F-18 [18F]FDOPA Radiopharmaceutical Name L-3,4-Dihydroxy-6-[18F]fluorophenylalanine. Also known as: Fluorodopa F18, 18F- fluorodopa, [18F]Fluorodopa, 18F-6-L-fluorodopa, [18F]-fluoro-L-DOPA, L-6-[18F]fluoro-3, 4- dihydroxyphenylalanine, 6-[18F]Fluoro-L-DOPA. 18 Abbreviations: FDOPA, -FDOPA. Radiopharmaceutical Image Normal Biodistribution Radiopharmaceutical Structure 18 The F-FDOPA biodistribution resembles the normal distribution of L-DOPA. It crosses the blood-brain barrier, where it is converted to 18F-Fluorodopamine by dopa decarboxylase. 18F-Fluorodopamine is stored intraneuronally in vesicles. Maximum intensity projection (left) and 2 coronal images of normal 18F-FDOPA biodistribution (uptake in basal ganglia, myocardium, mild uptake in skeletal muscle; excreted activity in urinary tract; uptake in pancreas was suppressed by premedication with carbidopa ) courtesy of Karel Pacak, MD, PhD (NICHD, NIH) Radionuclide 18F Half-life 109.7 minutes Emission Emission positron: Emax 1.656 MeV Developed by the SNMMI PET Center of Excellence and the Center for Molecular Imaging Innovation & Translation May 2013 - 1 Fluorodopa F-18 [18F]FDOPA MICAD http://www.ncbi.nlm.nih.gov/books/NBK23043/ Molecular Formula and Weight C9H10FNO4 2145.18 g/mole General Tracer Class Investigational Diagnostic PET Radiopharmaceutical in the US; approved for clinical use in some European countries under the name IASODopa® Target 1. Neurology/Psychiatry: Dopamine receptors in the brain (1-3) 2. Oncology: a) Amino acid (AA) transporters (a feature of many benign and malignant tumors); b) overexpression of DOPA decarboxylase is a characteristic feature of neuroendocrine tumors (NET); this enzyme is usually co-expressed with other neuroendocrine markers such as chromogranin-A (4).
    [Show full text]
  • In Vivo Imaging of Neurotransmitter Systems Using Radio Labeled Receptor Ligands Lawrence S
    ELSEVIER In Vivo Imaging of Neurotransmitter Systems Using Radio labeled Receptor Ligands Lawrence S. Kegeles, M.D., Ph.D., and J. John Mann, M.D. In vivo functional brain imaging, including global blood overview of the methodology of development and selection of flow, regional cerebral blood flow (rCBF), measured with radioligands for PET and SPECT is presented. Studies positron emission tomography (PET) and single photon involving PET and SPECT ligand methods are reviewed emission computed tomography (SPECT), and regional and their findings summarized, including recent work cerebral metabolic rate (rCMR) measured with demonstrating successive mutual modulation of deoxyglucose PET, have been widely used in studies of neurotransmitter systems. Kinetic and equilibrium analysis psychiatric disorders. These studies have found modest modeling are reviewed. The emerging methodology of differences and required large numbers of patients. measuring neurotransmitter release on activation, both Activation studies using rCBF or rCMR as indices of pharmacologically and by task performance, using ligand neuronal activity are more sensitive because patients act as methods is reviewed and proposed as a promising new their own control; however, findings localize regions of approach for studying psychiatric disorders. change but provide no data about specific neurotransmitter [Neuropsychopharmacology 17:293-307, 1997] systems. After a general discussion of the role of © 1997 American College of Neuropsychopharmacology. neurotransmitter systems in neuropsychiatric
    [Show full text]