Synthesis and biological evaluation of novel technetium-99m labeled phenylbenzoxazole derivatives as potential imaging probes for β-amyloid plaques in brain

Abstract

Two uncharged 99mTc-labeled phenylbenzoxazole derivatives were biologically evaluated as potential imaging probes for β-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 β-amyloid plaques on the sections of transgenic mouse, and showed high affinity for Aβ(1–42) aggregates (Ki=11.1nM and 14.3nM, respectively). Autoradiography in vitro indicated that [99mTc]6 clearly labeled β-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 2min), and quickly washed out from the brain (0.25% ID/g at 60min). 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.