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

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• 作者：Xuedan Wang ; Mengchao Cui ; ^{cmc@bnu.edu.cn} ; Pingrong Yu ; Zijing Li ; Yanping Yang ; Hongmei Jia ; Boli Liu ; ^{liuboli@bnu.edu.cn}
• 关键词：Alzheimer&rsquo ; s disease ; 尾-Amyloid plaque ; Technetium-99m ; Phenylbenzoxazole ; Imaging probe
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 July, 2012
• 卷：22
• 期：13
• 页码：4327-4331
• 文件大小：853 K

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 (K_i = 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.