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 β-amyloid (Aβ) 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 Aβ(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 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 Aβ 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 Aβ plaques was carried out using brain sections of AD model mice and an AD patient, the FPEG chalcone derivative 7c intensely labeled Aβ plaques. Taken together, the results suggest 7c to be a useful candidate PET tracer for detecting Aβ plaques in the brain of patients with AD.