Brain Imaging
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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. -
Effects of Stress-Induced Depression on Parkinson's Disease
Effects of stress-induced depression on Parkinson’s disease symptomatology A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Ph.D.) in the Graduate Program in Neuroscience of the College of Medicine 2011 By Ann Marie Hemmerle B.S., University of Dayton Advisor: Kim B. Seroogy, Ph.D. Committee Chair: Neil Richtand, M.D., Ph.D. James P. Herman, Ph.D. Kathy Steece-Collier, Ph.D. Aaron Johnson, Ph.D. Abstract Parkinson’s disease (PD) is a chronic neurodegenerative disorder that primarily affects dopaminergic neurons of the nigrostriatal pathway resulting in debilitating motor symptoms. Parkinson’s patients also have a high risk of comorbid depression, though this aspect of the disorder is less well studied. Understanding the underlying pathology of the comorbidity is important in improving clinical treatments and the quality of life for PD patients. To address this issue, we have developed a new model combining the unilateral striatal 6-hydroxydopamine lesion model of PD with the chronic variable stress model (CVS) of depression. Dysfunction of the hypothalamic-pituitary-adrenal axis and its relationship to depression symptomatology is well established. Stress dysfunction may also have a role in the etiology of preclinical PD non- motor symptoms, and later in the course of the disease, may worsen motor symptoms. The combined model allows us to test the hypothesis that experimental depression exacerbates PD symptoms and to ascertain the mechanisms behind the increased neuronal loss. In the first study, we examined several temporal paradigms of the combined model. -
Kinetic Modeling in Positron Emission Tomography
Ch23.qxd 28/8/04 2:05 PM Page 499 CHAPTER 23 Kinetic Modeling in Positron Emission Tomography EVAN D. MORRIS,* CHRISTOPHER J. ENDRES,† KATHLEEN C. SCHMIDT,‡ BRADLEY T. CHRISTIAN,§ RAYMOND F. MUZIC JR.,¶ RONALD E. FISHER|| *Departments of Radiology and Biomedical Engineering, Indiana University School of Medicine, Indianapolis, Indiana †Department of Radiology, Johns Hopkins University, Baltimore, Maryland ‡Laboratory of Cerebral Metabolism, NIMH, Bethesda, Maryland §Wright State University, Kettering Medical Center, Dayton, Ohio ¶Departments of Radiology, Oncology and Biomedical Engineering, Case Western Reserve University, Nuclear Medicine, University Hospitals Cleveland, Cleveland, Ohio ||The Methodist Hospital and Department of Radiology and Neuroscience, Baylor College of Medicine, Houston, Texas I. Introduction used in the two most ubiquitous applications of PET: imag- II. The One-Compartment Model: Blood Flow ing of blood flow and glucose metabolism. We also examine III. Positron Emission Tomography Measurements of the use of PET to image specific receptor molecules, which Regional Cerebral Glucose Use capitalizes on the unique specificity of PET. IV. Receptor–Ligand Models Supplied with single (static) PET images and no kinetic V. Model Simplifications model to aid in their interpretation, one is confined to asking VI. Limitations to Absolute Quantification questions that can be answered only on the basis of spatial VII. Functional Imaging of Neurochemistry—Future Uses information such as: Where is glucose being used? Where VIII. A Generalized Implementation of the Model are particular receptor molecules located within the brain or Equations the heart? With the acquisition of dynamic (time-sequence) imaging data and the application of kinetic models, one can pose many additional quantitative questions based on temporal I. -
Assessment of Cardiac Amyloidosis with 99MTC- Pyrophosphate (PYP) Quantitative Spect
Assessment of Cardiac Amyloidosis With 99MTC- pyrophosphate (PYP) Quantitative Spect Chao Ren Peking Union Medical College Hospital Jingyun Ren Peking Union Medical College Hospital Zhuang Tian Peking Union Medical College Hospital Yanrong Du Peking Union Medical College Hospital Zhixin Hao Peking Union Medical College Hospital Zongyao Zhang Chinese Academy of Medical Sciences & Peking Union Medical College Fuwai Hospital Wei Fang Chinese Academy of Medical Sciences & Peking Union Medical College Fuwai Hospital Fang Li Peking Union Medical College Hospital Shuyang Zhang Peking Union Medical College Hospital Bailing Hsu University of Missouri-Columbia Li Huo ( [email protected] ) Peking Union Medical College Hospital https://orcid.org/0000-0003-1216-083X Original research Keywords: ATTR cardiomyopathy, 99mTc-PYP quantitative SPECT, standardized uptake value, diagnostic feasibility, the operator reproducibility Posted Date: June 5th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-32649/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/25 Version of Record: A version of this preprint was published on January 7th, 2021. See the published version at https://doi.org/10.1186/s40658-020-00342-7. Page 2/25 Abstract Background: 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from lightchain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT. Method:Thirty-seven consecutive patients underwent a99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). -
Epilepsy & Seizure
Epilepsy & Seizure Journal of Japan Epilepsy Society Vol.4 No.1 (2011) pp.15-25 Original Article Usefulness of 123I-iomazenil SPECT for childhood focal epilepsies 1) 1) 1) 1) Kentaro Okamoto, MD , Hirokazu Oguni, MD , Yoshiko Hirano, MD , Makiko Osawa, MD 1Department of Pediatrics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan Key words: focal epilepsy, children, 123I-iomazenil SPECT, epileptic foci Published online July 29, 2011 Abstract Purpose: We investigated the usefulness of obtained from visualization of IMZ-SPECT 123I-iomazenil (IMZ-) SPECT to detect epilep- images and those speculated based on a com- tic foci in children with symptomatic focal bination of clinical manifestations, EEG find- epilepsy (SFE). ings, and brain MRI. We then verified the Subjects: 21 children with SFE who under- concordance of the results between the two went IMZ-SPECT to identify the epileptic fo- methods. cus were studied. Results: There was concordance in both later- Methods: We retrospectively compared the alization and localization in 9/12 patients with localization and lateralization of epileptic foci temporal lobe epilepsy (75%), in 2/5 patients Correspondence to: Hirokazu Oguni, MD, Department of Pediatrics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan Tel. 81-3-3353-8111, Fax. 81-3-5269-7338, [email protected] 15 Kentaro Okamoto, et al. IMZ-SPECT for childhood epilepsy with frontal lobe epilepsy (40%), and in 2/4 interictal/ictal cerebral blood flow single pho- patients with parieto-occipital lobe epilepsy ton emission computed tomography (SPECT) (50%). -
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. -
[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, -
(19) United States (12) Patent Application Publication (10) Pub
US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist. -
Radiolabelled Molecules for Brain Imaging with PET and SPECT • Peter Brust Radiolabelled Molecules for Brain Imaging with PET and SPECT
Radiolabelled Molecules for Brain Imaging with PET and SPECT Radiolabelled • Peter Brust Molecules for Brain Imaging with PET and SPECT Edited by Peter Brust Printed Edition of the Special Issue Published in Molecules www.mdpi.com/journal/molecules Radiolabelled Molecules for Brain Imaging with PET and SPECT Radiolabelled Molecules for Brain Imaging with PET and SPECT Editor Peter Brust MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editor Peter Brust Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf Germany Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Molecules (ISSN 1420-3049) (available at: https://www.mdpi.com/journal/molecules/special issues/PET SPECT). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03936-720-7 (Hbk) ISBN 978-3-03936-721-4 (PDF) c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editor .............................................. vii Preface to ”Radiolabelled Molecules for Brain Imaging with PET and SPECT” ........ -
Imaging in Parkinson's Disease
Clinical Medicine 2016 Vol 16, No 4: 371–5 CME MOVEMENT DISORDERS I m a g i n g i n P a r k i n s o n ’ s d i s e a s e Authors: G e n n a r o P a g a n o , A F l a v i a N i c c o l i n i B a n d M a r i o s P o l i t i s C The clinical presentation of Parkinson’s disease (PD) Abnormal intra-neuronal (Lewy bodies) and intra-neuritic is heterogeneous and overlaps with other conditions, (Lewy neurites) deposits of fibrillary aggregates are currently including the parkinsonian variant of multiple system considered the key neuropathological alterations in PD. atrophy (MSA-P), progressive supranuclear palsy (PSP) and The majority of these aggregates, mainly composed of alpha essential tremor. Imaging of the brain in patients with (α)−synuclein, are located at presynaptic level and impair ABSTRACT parkinsonism has the ability to increase the accuracy of axonal trafficking, resulting in a series of noxious events that differential diagnosis. Magnetic resonance imaging (MRI), cause neuronal damage to the substantia nigra pars compacta single photon emission computed tomography (SPECT) and with a subsequent dopaminergic denervation of the striatum. positron emission tomography (PET) allow brain imaging The cardinal motor features of PD (bradykinesia and rigidity, of structural, functional and molecular changes in vivo in with or without resting tremor) manifest after a substantial patients with PD. Structural MRI is useful to differentiate denervation of substantia nigra, which is associated with about PD from secondary and atypical forms of parkinsonism. -
Natural History, MRI Morphology, and Dopamine Receptor Imaging with 123IBZM-SPECT
J7ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:1047-1056 1047 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.9.1047 on 1 September 1994. Downloaded from Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT J B Schulz, T Klockgether, D Petersen, M Jauch, W Muiller-Schauenburg, S Spieker, K Voigt, J Dichgans Abstract of the intermediolateral cell columns of the Sixteen patients with a clinical diagnosis spinal cord. All of these changes are not neces- of probable multiple system atrophy sarily found in each patient with MSA. In (MSA) were examined clinically by MRI some patients, degeneration affects mainly the and by 523I-iodobenzamide single photon basal ganglia, whereas in others the ponto- emission computed tomography (IBZM- cerebellar system or the spinal cord are more SPECT). The clinical records of another affected. Therefore, evidence of cell degenera- 16 patients were also analysed retrospec- tion and gliosis in at least three of the following tively. On the basis of their clinical pre- anatomical structures is thought to be suffi- sentation, patients were subdivided into cient for the neuropathological diagnosis of those with prominent parkinsonism MSA: striatum, substantia nigra, Purkinje (MSA-P, n = 11) and those with promi- cell layer of the cerebellar cortex, pontine nent cerebellar ataxia (MSA-C, n = 21). nuclei, inferior olives, and intermediolateral Autonomic symptoms were present in all cell columns of the spinal cord.'4 Striatum or patients and preceded the onset of motor substantia nigra must be one of these areas.5 symptoms in 63% of patients. -
Vizamyl, INN-Flutemetamol (18F)
26 June 2014 EMA/546752/2014 Committee for Medicinal Products for Human Use (CHMP) Vizamyl flutemetamol (18F) Procedure No. EMEA/H/C/002553 Marketing authorisation holder: GE HEALTHCARE LIMITED Assessment report for an initial marketing authorisation application Assessment report as adopted by the CHMP with all commercially confidential information deleted 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, 2014. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ...................................................................................... 7 1.2. Manufacturers ...................................................................................................... 8 1.3. Steps taken for the assessment of the product ......................................................... 8 2. Scientific discussion ................................................................................ 9 2.1. Introduction......................................................................................................... 9 2.2. Quality aspects .................................................................................................. 11 2.2.1. Introduction ...................................................................................................