Ono Masahiro, Hori Miyuki, Haratake Mamoru, Tomiyama Takami, Mori Hiroshi, Nakayama Morio
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Bioorg Med Chem. 2007 Oct 1;15(19):6388-96. doi: 10.1016/j.bmc.2007.06.055. Epub 2007 Jul 4.
A series of novel chalcones and their related derivatives were synthesized and evaluated as beta-amyloid imaging probes. In the structure-activity relationship of binding affinities to synthetic Abeta(1-42) aggregates, compound 14 displayed the highest binding affinity in vitro. beta-Amyloid plaques in the Alzheimer's model mouse brain were visualized with 14. In biodistribution studies using normal mice, [(125)I]14 showed good brain uptake (2.56% ID/g, 2min postinjection) and rapid washout from the brain (0.21% ID/g, 60min postinjection). These results suggest that [(125)I]14 should be further investigated as a potentially useful beta-amyloid imaging probe.
合成了一系列新型查耳酮及其相关衍生物，并将其作为β-淀粉样蛋白成像探针进行评估。在与合成的Aβ(1-42)聚集体的结合亲和力构效关系中，化合物14在体外表现出最高的结合亲和力。用化合物14可观察到阿尔茨海默病模型小鼠脑中的β-淀粉样斑块。在使用正常小鼠的生物分布研究中，[(125)I]14显示出良好的脑摄取（注射后2分钟为2.56% ID/g）以及从脑中快速清除（注射后60分钟为0.21% ID/g）。这些结果表明，[(125)I]14作为一种潜在有用的β-淀粉样蛋白成像探针应进一步研究。
