(E)-5-styryl-1H-indole and (E)-6-styrylquinoline derivatives serve as probes for β-amyloid plaques

Abstract

We report the synthesis and biological evaluation of novel (E)-5-styryl-1H-indole and (E)-6-styrylquinoline derivatives as probes for imaging β-amyloid (Aβ) plaques. These derivatives showed binding affinities for Aβ 1-40 aggregates with Ki values varying from 4.1 to 288.4 nM. (E)-5-(4-iodostyryl)-1H-indole (8) clearly stained Aβ plaques in the brain sections of Alzheimer's disease (AD) model mice (APP/PS1). Furthermore, autoradiography for [ 125I]8 displayed intense and specific labeling of Aβ plaques in the brain sections mentioned above with low background. In biodistribution experiments using normal mice [ 125I]8 showed high initial brain uptake followed by rapid washout (4.27 and 0.64% ID/g at 2 and 30 min post injection, respectively). These findings suggests that [ 123I]8 may be a potential SPECT imaging agent for detecting Aβ plaques in AD brain. © 2012 by the authors.