Fluoro-pegylated chalcones as positron emission tomography probes for in vivo imaging of -amyloid plaques in Alzheimer's disease.

This paper describes the synthesis and biological evaluation of fluoro-pegylated (FPEG) chalcones for the imaging of -amyloid (A) plaques in patients with Alzheimer's disease (AD). FPEG chalcone derivatives were prepared by the aldol condensation reaction. In binding experiments conducted in vitro using A(1-42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed higher Ki values (20-50 nM) than those having a monomethylamino or a primary amine group. When the biodistribution of 11C-labeled FPEG chalcone derivatives having a dimethyamino group was examined in normal mice, all four derivatives were found to display sufficient uptake for imaging A plaques in the brain. 18F-labeled 7c also showed good uptake by and clearance from the brain, although a slight difference between the 11C and 18F tracers was observed. When the labeling of A plaques was carried out using brain sections of AD model mice and an AD patient, the FPEG chalcone derivative 7c intensely labeled A plaques. Taken together, the results suggest 7c to be a useful candidate PET tracer for detecting A plaques in the brain of patients with AD.