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In Vivo Imaging of Amyloid Deposition in Alzheimer Disease Using the Radioligand 18 F-AV-45 (Flobetapir F 18)
Open accessAbstract
UNLABELLED: An (18)F-labeled PET amyloid-beta (Abeta) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease (AD) pathology. Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine ((18)F-AV-45 or florbetapir [corrected] F 18). METHODS: An open-label, multicenter brain imaging, metabolism, and safety study of (18)F-AV-45 was performed on 16 patients with AD (Mini-Mental State Examination score, 19.3 +/- 3.1; mean age +/- SD, 75.8 +/- 9.2 y) and 16 cognitively healthy controls (HCs) (Mini-Mental State Examination score, 29.8 +/- 0.45; mean age +/- SD, 72.5 +/- 11.6 y). Dynamic PET was performed over a period of approximately 90 min after injection of the tracer (370 MBq [10 mCi]). Standardized uptake values and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps for a subset of subjects. RESULTS: Valid PET data were available for 11 AD patients and 15 HCs. (18)F-AV-45 accumulated in cortical regions expected to be high in Abeta deposition (e.g., precuneus and frontal and temporal cortices) in AD patients; minimal accumulation of the tracer was seen in cortical regions of HCs. The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 min after administration, reaching a plateau within 50 min. The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/- 0.175 for patients with AD versus 1.25 +/- 0.177 for HCs. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r = 0.58-0.88, P < 0.005) and were significantly greater for AD patients than for HCs in cortical regions but not in subcortical white matter or cerebellar regions. No clinically significant changes in vital signs, electrocardiogram, or laboratory values were observed. CONCLUSION: (18)F-AV-45 was well tolerated, and PET showed significant discrimination between AD patients and HCs, using either a parametric reference region method (DVR) or a simplified SUVR calculated from 10 min of scanning 50-60 min after (18)F-AV-45 administration.
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“Positron emission tomography (PET) ligands have been shown to provide a minimally invasive estimate of the neuropathological features of AD, such as Aβ neuritic plaque deposition.15,16,17,18”
From Positron Emission Tomography Imaging With [ 18 F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [15]
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“Amyloid imaging biomarkers, obtained via positron emission tomography imaging with Pittsburgh compound B (11C-PiB)24 or Florbetapir F 18 (18F-AV-45)25 were available for 54 individuals, and all were positive.”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [25]
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Metadata
- Authors
- Wong, D. F., Rosenberg, P. B., Zhou, Y., Kumar, A., Raymont, V., Ravert, H. T., Dannals, R. F., Nandi, A., Brašić, J. R., Ye, W., Hilton, J., Lyketsos, C., Kung, H. F., Joshi, A. D., Skovronsky, D. M., & Pontecorvo, M. J.
- Affiliations
- Johns Hopkins University (US)
- University of Pennsylvania (US)
- Eli Lilly (United States) (US)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2010-05-25
- Volume
- 51
- Issue
- 6
- Pages
- 913-920
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- PMC
- PMC3101877
- OpenAlex
- W2040174321
- Cited by
- 684
- References
- 35
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 17 · 2023: 25 · 2022: 32 · 2021: 42 · 2020: 43 · 2019: 31 · 2018: 46 · 2017: 54 · 2016: 56 · 2015: 50 · 2014: 60 · 2013: 64 · 2012: 57
- FWCI
- 40.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- Vanderbilt University
- National Institutes of Health
- Avid Radiopharmaceuticals
- National Institute on Alcohol Abuse and Alcoholism (R01AA012839, AA012839)
- National Institute on Aging (K08AG029157, P50AG005146)
- National Institute of Mental Health (R01MH078175, MH 078175)
- National Institute on Drug Abuse (K24DA000412)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- Alzheimer's disease, amyloid-beta deposition, 18F-florbetapir, positron emission tomography, radioligands, amyloid imaging, distribution volume ratio, standardized uptake value ratio, dynamic PET, tracer metabolism, brain amyloid imaging, late-life cognitive impairment, cerebellum
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Aniline Compounds, Brain, Ethylene Glycols, Female, Fluorine Radioisotopes, Humans, Male, Radiometry, Whole-Body Irradiation, Case-Control Studies, Positron-Emission Tomography, Drug-Related Side Effects and Adverse Reactions
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