Ono Masahiro, Haratake Mamoru, Mori Hiroshi, Nakayama Morio
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-Machi, Nagasaki, Japan.
Bioorg Med Chem. 2007 Nov 1;15(21):6802-9. doi: 10.1016/j.bmc.2007.07.052. Epub 2007 Aug 21.
A novel series of chalcone derivatives for in vivo imaging beta-amyloid plaques in the brain of Alzheimer's disease (AD) were synthesized and characterized. When in vitro binding studies using Abeta aggregates were carried out with chalcone derivatives, the binding affinities for Abeta aggregate varied from 3 to 105 nM. The radioiodinated chalcones were successfully prepared through an iododestannylation reaction from the corresponding tributyltin derivatives using hydrogen peroxide as the oxidant in high yields and with high radiochemical purities. Biodistribution studies in normal mice after iv injection of the radioiodinated chalcones displayed high brain uptake (2.0-4.7% ID/g at 2 min) and rapid clearance from the brain (0.2-0.6% ID/g at 30 min), which is highly desirable for amyloid imaging agents. The results in this study suggest that the novel radioiodinated chalcones may be useful amyloid imaging agents for detecting beta-amyloid plaques in the brain of AD.
合成并表征了一系列用于体内成像阿尔茨海默病（AD）大脑中β-淀粉样斑块的新型查尔酮衍生物。当使用查尔酮衍生物对β-淀粉样蛋白聚集体进行体外结合研究时，其对β-淀粉样蛋白聚集体的结合亲和力在3至105 nM之间变化。以过氧化氢为氧化剂，通过碘脱锡反应，从相应的三丁基锡衍生物中成功制备了放射性碘化查尔酮，产率高且放射化学纯度高。静脉注射放射性碘化查尔酮后在正常小鼠体内进行的生物分布研究显示，大脑摄取率高（2分钟时为2.0-4.7%ID/g），且从大脑中清除迅速（30分钟时为0.2-0.6%ID/g），这对于淀粉样蛋白成像剂来说是非常理想的。本研究结果表明，新型放射性碘化查尔酮可能是用于检测AD大脑中β-淀粉样斑块的有用的淀粉样蛋白成像剂。
