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)

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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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Core Alzheimer’s disease cerebrospinal fluid biomarker assays are not affected by aspiration or gravity drip extraction methods
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“Both FDG and AV45 are well-established imaging biomarkers 44,45 in medical literature.”
A Novel 18F Labelled Imidazo-oxazolopyridine Derivative as b-Amyloid Imaging Agent: Synthesis and Preliminary Evaluation
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Retracted
Cross-validation of Quantitative Analytical Software Using 18F-florbetapir PET Imaging
Wagatsuma, K., Miwa, K., Sakata, M., Ishibashi, K., & Ishii, K. (2021) · Japanese Journal of Radiological Technology · doi:10.6009/jjrt.2021_jsrt_77.1.32 · Cited by 2
Multimodal brain age estimates relate to Alzheimer disease biomarkers and cognition in early stages: a cross-sectional observational studyPreprint
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“Amyloid burden was imaged with positron emission tomography (PET) using [11C]-Pittsburgh 153 Compound B (PIB) (36) or [18F]-Florbetapir (AV45) (37).”
MethodInfluential
Aβ Imaging in Aging, Alzheimer’s Disease, and Other Neurodegenerative Conditions
Villemagne, V. L., Doré, V., Burnham, S. C., & Rowe, C. C. (2020) · Springer eBooks · doi:10.1007/978-3-030-53168-3_10 · Cited by 2
A Pilot Study on Cerebral Blood Flow and Mini-Mental State Examination to Predict Amyloid Deposition in Preclinical Alzheimer’s Disease
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Fairness-Aware Estimation of Graphical Models
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Affective Symptoms and Amyloid Plaques: Antidepressant Response and Clinical Outcome Associated With Brain Amyloid Load in a 2-Year Cohort of Nondemented Older Adults With Depression—The ASAP Study
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Comprehensive and stratified meta-analysis of diffusion tensor image analysis along the perivascular space in Alzheimer's disease: Linking glymphatic dysfunction with cognitive decline and amyloid pathology
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Amyloid PET quantification with deep learning segmentation models without MRI
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Disentangling amyloid polymorphs in normal aging and Alzheimer's disease using dual-probe spectral imaging
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“In this study we used [ 3 H]florbetaben to probe binding of the tracer on human AD brain sections in the absence or presence of nivegacetor and another established A β PET tracer, florbetapir (Wong et al., 2010).”
Diagnosis of Dementia Using Nuclear Medicine Imaging Modalities
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Central Nervous System
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PET Chemistry: Radiopharmaceuticals
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Amyloid PET: Its diagnostic potential compared to FDG
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“Recently, [18F]AV-45 PET imaging was performed in AD patients and control subjects (Wong et al., 2010).”
MethodResult
Harmonisation of PET imaging features with different amyloid ligands using machine learning-based classifier
Kang, S. H., Kim, J., Kim, J. P., Cho, S. H., Choe, Y. S., Jang, H., Kim, H. J., Koh, S., Na, D. L., Seong, J., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05499-6 · Cited by 1
Central Nervous System
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Chapter 8. Dementia and Mild Neurocognitive Disorders
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Self-citation
Multicenter Experience with Good Manufacturing Practice Production of [11C]PiB for Amyloid Positron Emission Tomography Imaging
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“…high performance liquid chromatography (HPLC) [5,13–15, 20,21 ], where compound The short t ½ of 11 C has also led to the development of 18 F-tracers for A β imaging, such as florbetaben [23], florbetapir [24], flutemetamol (“[ 18 F]PiB”) [25], and NAV4694 [26], as the t ½ for 18 F is 109.77 min.”
BackgroundInfluential
Animal Models for Brain Research
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À propos des ivacaftor, bédaquiline, florbétapir F18 et propranolol
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Nuclear medicine techniques for the diagnosis of cardiac amyloidosis: the state of the art
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Positron Emission Tomography
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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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