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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“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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Method
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“Ab can be visualized using [(18)F] florbetapir positron emission tomography (PET).(3,4) Accurate quantification of Ab is important for identifying subtle amyloid accumulation, as well as for monitoring disease progression and evaluating (experimental) anti-amyloid disease-modifying therapies.”
Method
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Method
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Background
Alzheimer’s Disease - An Update
Rahman, A., Salam, F., Islam, M. A., Anwarullah, A., Islam, M. R., Miah, M. N. A., Saha, U. K., & Ali, Z. (2013) · Bangladesh Journal of Neuroscience · doi:10.3329/bjn.v28i1.17193 · Cited by 10
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“…appropriate uptake of [ 18 F]-Florbetazine in the brain cortex for both HCs and AD patients, similar to that found by other A β radioligands ( Wong et al. , 2010 ; Rowe et al., 2008; Nelissen et al. , 2009 ; Ito et al. , 2014 ; Jur ´ eus et al., 2010; Furumoto et al., 2013; Hooshyar Yousefi…”
Result
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Radiopharmaceuticals for Assessment of Altered Metabolism and Biometal Fluxes in Brain Aging and Alzheimer’s Disease with Positron Emission Tomography
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“In a phase 1 trial of (18)F-florbetapir in 16 cognitively normal volunteers and 16 patients with AD, patients with AD showed selective retention of tracer in cortical areas expected to be high in amyloid deposition, whereas cognitively normal controls showed rapid washout from these areas, with only minimal cortical t…”
Background
Prediction of the Clinical SUV Ratio in Amyloid PET Imaging Using a Biomathematic Modeling Approach Toward the Efficient Development of a Radioligand
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“Some of these have successfully been applied in human PET studies: for example, 11C-Pittsburgh compound B (PIB) (2), 11C-labeled 2-(2-[2dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (11C-BF-227) (3–6), 11C-labeled 5-(6-{[tert-butyl(dimethyl)silyl] oxy}-1,3-benzothiazol-2-yl)pyridin-2-amine (11C-AZ…”
Dual-phase 18 F-florbetapir positron emission tomography in patients with primary progressive aphasia, Alzheimer's disease, and healthy controls: A preliminary study
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“This is an open access article under the commons.org/licenses/by-nc-nd/4.0/). semantic dementia; dementia; clinical neurology; diagnostic imaging; radiology; nuclear medicine and medical imaging Please cite this article in press as: K progressive aphasia, Alzheimer’s dise http://dx.doi.org/10.1016/j.jfma.20 Results: E…”
ResultInfluential
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“…tracer Target Purpose [11C]-PIB (Rostomian et al., 2011) Amyloid plaque Diagnosis of Alzheimer’s disease and efficacy on A plaques [18F]-AV45 (Wong et al., 2010) Amyloid plaque Diagnosis of Alzheimer’s disease and efficacy measurement of A plaques [18F]-FK960 (Noda et al., 2003a)…”
Background
Comparison of the Amyloid Load in the Brains of Two Transgenic Alzheimer’s Disease Mouse Models Quantified by Florbetaben Positron Emission Tomography
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“Positron emission tomography (PET) tracers targeted to Aß including 18F-AV-45 (Florbetapir) have clinical utility in the evaluation of patients with suspected AD (21).”
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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