Synthesis and characterization of novel phenylindoles as potential probes for imaging of -amyloid plaques in the brain.


We synthesized a novel series of phenylindole (PI) derivatives and evaluated their biological activities as probes for imaging A plaques in vivo. The affinity for A plaques was assessed by an in vitro-binding assay using pre-formed synthetic A aggregates. 2-phenyl-1H-indole (2-PI) derivatives showed high affinity for A42 aggregates with Ki values ranging from 4 to 32 nM. 2-PI derivatives clearly stained A plaques in an animal model of AD. In biodistribution experiments using normal mice, 2-PI derivatives displayed sufficient uptake for imaging, ranging from 1.1% to 2.6% ID/g. Although additional modifications are necessary to improve uptake by and clearance from the brain, 2-PI derivatives may be useful as a backbone structure to develop novel A imaging agents.