Novel imaging agents for β-amyloid plaque based on the N-benzoylindole core

We report the synthesis and evaluation of a series of N-benzoylindole derivatives as novel potential imaging agents for β-amyloid plaques. In vitro binding studies using Aβ1-40 aggregates versus [125I]TZDM showed that all these derivatives demonstrated high binding affinities (Ki values ranged from 8.4 to 121.6 nM). Moreover, two radioiodinated compounds [125I]7 and [125I]14 were prepared. Autoradiography for [125I]14 displayed intense and specific labeling of Aβ plaques in the brain sections of AD model mice (C57, APP/PS1) with low background. In vivo biodistribution in normal mice exhibited sufficient initial brain uptake for imaging (2.19% and 2.00% ID/g at 2 min postinjection for [125I]7 and [125I]14, respectively). Although additional modifications are necessary to improve brain uptake and clearance from the brain, the N-benzoylindole may be served as a backbone structure to develop novel β-amyloid imaging probes.