摘要
Two uncharged 99mTc-labeled phenylbenzoxazole derivatives were biologically evaluated as potential imaging probes for 尾-amyloid plaques. The 99mTc and corresponding rhenium complexes were synthesized by coupling monoamine-monoamide dithiol (MAMA) and bis(aminoethanethiol) (BAT) chelating ligand via a pentyloxy spacer to phenylbenzoxazole. The fluorescent rhenium complexes 6 and 9 selectively stainined the 尾-amyloid plaques on the sections of transgenic mouse, and showed high affinity for A尾(1-42) aggregates (Ki = 11.1 nM and 14.3 nM, respectively). Autoradiography in vitro indicated that [99mTc]6 clearly labeled 尾-amyloid plaques on the sections of transgenic mouse. Biodistribution experiments in normal mice revealed that [99mTc]6 displayed moderate initial brain uptake (0.81%ID/g at 2 min), and quickly washed out from the brain (0.25%ID/g at 60 min). The preliminary results indicate that the properties of [99mTc]6 are promising, although additional refinements are needed to improve the ability to cross the blood-brain barrier.