Cited by 697Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

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In Vivo Imaging of Amyloid Deposition in Alzheimer Disease Using the Radioligand 18 F-AV-45 (Flobetapir F 18)

Open access

Wong, Dean F., Rosenberg, Paul B., Zhou, Yun, Kumar, Anil, Raymont, Vanessa, Ravert, Hayden T., Dannals, Robert F., Nandi, Ayon, Brašić, James R., Ye, Weiguo, Hilton, John, Lyketsos, Constantine, Kung, Hank F., Joshi, Abhinay D., Skovronsky, Daniel M., Pontecorvo, Michael J.·2010·Journal of Nuclear Medicine

DOI 10.2967/jnumed.109.069088PMC PMC3101877

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Abstract

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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“Patients with AD had to be older than 50 y and have a probable diagnosis of AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association, with a Mini-Mental State Examination (MMSE) score of between 10 and 24, inclusively (1…”
Method
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“This finding is consistent with the known localization of Ab in these areas in postmortem tissue (23), with recent literature suggesting the precuneus is involved in integrative functions including visual spatial coordination and working memory retrieval (24)—and with results from other Ab radiotracers (9,25).”
Result
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“This pattern is similar to that previously reported for 11CPIB (21,22) and 18F-BAY94-9172 (9).”
BackgroundResult
Cerebrospinal Fluid tau/β-Amyloid42 Ratio as a Prediction of Cognitive Decline in Nondemented Older Adults
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“Although cerebrospinal fluid Ab levels are reliably decreased in AD (6), cerebrospinal fluid studies are inevitably indirect markers.”
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-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease
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Self-citation
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BackgroundMethodInfluential
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BackgroundSelf-citation
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Background
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Background
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Background
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Method
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Background
Coordination Chemistry of Bifunctional Chemical Agents Designed for Applications in 64Cu PET Imaging for Alzheimer’s Disease
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Background
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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: Wong, Dean F.
Rosenberg, Paul B.
Zhou, Yun
Kumar, Anil
Raymont, Vanessa
Ravert, Hayden T.
Dannals, Robert F.
Nandi, Ayon
Brašić, James R.
Lyketsos, Constantine
Kung, Hank F.
Pontecorvo, Michael J.
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
DOI: 10.2967/jnumed.109.069088
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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In Vivo Imaging of Amyloid Deposition in Alzheimer Disease Using the Radioligand 18 F-AV-45 (Flobetapir F 18)

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