In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (flobetapir F 18)

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

Research output: Contribution to journalArticlepeer-review

Abstract

An 18F-labeled PET amyloid-β (Aβ) 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- 18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl) vinyl)-N-methyl benzenamine (18F-AV-45 or flobetapir F 18). Methods: An open-label, multicenter brain imaging, metabolism, and safety study of 18F-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 availablefor 11ADpatients and15HCs. 18F-AV-45 accumulated in cortical regions expected to be high in Aβ 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, reachinga plateauwithin50min. The 10-minperiod 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: 18F-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 18F-AV-45 administration. COPYRIGHT

Original languageEnglish (US)
Pages (from-to)913-920
Number of pages8
JournalJournal of Nuclear Medicine
Volume51
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Aging
  • Alzheimer disease
  • Biomarkers
  • Dementia
  • F
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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