99mTc-labeled-2-arylbenzoxazole derivatives as potential Aβ imaging probes for single-photon emission computed tomography

Four neutral Tc-99m/Re-labeled 2-arylbenzoxazole derivatives conjugated to bis (aminoethanethiol) (BAT) chelating ligand via a short propoxy spacer were synthesized and evaluated. In vitro binding assay showed that they displayed binding affinities to A beta(1-42) aggregates (K-i = 15.86-393.18 nM). In vitro autoradiography studies further confirmed the high and specific binding of [Tc-99m]20 to beta-amyloid plaques on brain sections of transgenic mice. Biodistribution study of [Tc-99m]17-20 in normal mice displayed moderate initial brain uptake (0.96-1.55%ID/g at 2 min), and fast washed out from the brain (0.14-0.40%ID/g at 60 min), especially for [Tc-99m]20 with a brain(2min)/brain(60min) ratio of 8.86. Taken together, these preliminary data suggested that [Tc-99m]20 may be a potential imaging probe for detecting amyloid plaques in the brain. (C) 2014 Elsevier Masson SAS. All rights reserved.