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 <i>K</i><sub>i</sub> values (20−50 nM) than those having a monomethylamino or a primary amine group. When the biodistribution of <sup>11</sup>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 Aβ plaques in the brain. <sup>18</sup>F-labeled <b>7c</b> also showed good uptake by and clearance from the brain, although a slight difference between the <sup>11</sup>C and <sup>18</sup>F 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 <b>7c</b> intensely labeled Aβ plaques. Taken together, the results suggest <b>7c</b> to be a useful candidate PET tracer for detecting Aβ plaques in the brain of patients with AD.