Synthesis and biological evaluation of 18F-labled 2-phenylindole derivatives as PET imaging probes for β-amyloid plaques

A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as beta-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for A beta(1-42) aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with F-18 ([F-18]1a) for its high affinity (K-i = 28.4 nM), which was also confirmed by in vitro autoradiography experiments on brain sections of transgenic mouse (C57BL6, APPswe/PSEN1, 11 months old, male). In vivo biodistribution experiments in normal mice showed that this radiotracer displayed high initial uptake (5.82 +/- 0.51% ID/g at 2 min) into and moderate washout (2.77 +/- 0.31% ID/g at 60 min) from the brain. [F-18]1a could be developed as a promising new PET imaging probe for A beta plaques although necessary modifications are still needed. (C) 2013 Elsevier Ltd. All rights reserved.