In Vivo Imaging of Amyloid Deposition in Alzheimer’s Disease using the Novel Radioligand [18F]AV-45 (Florbetapir F 18)

By D. Wong, P. Rosenberg, Yun Zhou, Anil Kumar, V. Raymont, H. Ravert, R. Dannals, A. Nandi, James Robert Brašić, W. Ye and 6 more. Journal of Nuclear Medicine, 2010

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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 available for 11 AD patients and 15 HCs. 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, 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: 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.

Subfields: Physiology, Psychiatry and Mental health, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/e702023c0085ac032779479a60bcc16a7b0e657a

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Citations in the corpus

Diagnosis of Early Alzheimer's Disease: Clinical Practice in 2021 (2021, positive): “…increased cortical retention of the tracer in regions of Aβ deposition within the brain (74), thus confirming the presence of Aβ plaques in the brain (74, 75) and directly quantify brain amyloid pathology (76), thus making it a useful tool to supplement a clinical battery to diagnose AD (3, 74).”
Brain imaging in Alzheimer disease. (2012, methodology): “…studies using each of the fluorine-18-labelled tracers, [F-18]florbetaben (18F-BAY94-9172 or AV-1; Rowe et al. 2008), [F-18]florbetapir (AV-45; Wong et al. 2010; Clark et al. 2011) and [F-18]flu- temetamol (3 0 F-PiB or GE-067; Nelissen et al. 2009; Vandenberghe et al. 2010) in AD patients.”
Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases. (2018, background): “PET studies that use tracers that specifically bind amyloid (C11PiB [Klunk et al. 2004; Ikonomovic et al. 2008], F18-florbetapir [Wong et al. 2010; Clark et al. 2011, 2012], F18-flutemetamol [Vandenberghe et al. 2010; Wolk et al. 2011], and F18-florbetaben [Rowe et al. 2008]) can noninvasively…”