Fluoro-pegylated Chalcones as Positron Emission Tomography Probes for in Vivo Imaging of β-Amyloid Plaques in Alzheimer's Disease

This paper describes the synthesis and biological evaluation of fluoro-pegylated (FPEG) chalcones for the imaging of beta-amyloid (A beta) 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 beta(1-42) aggregates, the FPEG chalcone derivatives having a dimethylamino group showed higher K(i) values (20-50 nM) than those having a monomethylamino or a primary anline group. When the biodistribution of (11)C-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 beta plaques in the brain. (18)F-labeled 7c also showed good uptake by and clearance from the brain, although a slight difference between the (11)C and (18)F tracers was observed. When the labeling of A beta plaques was carried out using brain sections of AD model mice and an AD patient, the FPEG chalcone derivative 7c intensely labeled A beta plaques. Taken together, the results suggest 7c to be a useful candidate PET tracer for detecting A beta plaques in the brain of patients with AD.