Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the Brain

beta-amyloid plaques (A beta plaques) in the brain, containing predominantly fibrillary A beta peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the A beta plaques in the living human brain are potentially valublle as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-F-18-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl) vinyl)-N-methyl benzenamine (F-18-AV-45) is such as an agent currently in phase III clinical studies for PET of A beta plaques in the brain. Methods: In vitro binding of F-18-AV-45 to A beta plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of F-18-AV45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with A beta aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of F-18-AV-45 was evaluated. Results: F-18-AV-45 displayed a high binding affinity and specificity to A beta plaques (K-d, 3.72 +/- 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. F-18-AV-45 displayed excellent binding affinity to A beta plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that F-18-AV-45 may be a useful PET agent for detecting A beta plaques in the living human brain.