Ono Masahiro, Yoshida Naoko, Ishibashi Kenichi, Haratake Mamoru, Arano Yasushi, Mori Hiroshi, Nakayama Morio
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
J Med Chem. 2005 Nov 17;48(23):7253-60. doi: 10.1021/jm050635e.
In vivo imaging of beta-amyloid (A beta) peptide aggregates in the brain may lead to early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of AD treatment. The purpose of this study was to develop novel amyloid imaging agents based on flavone as a core structure. Radioiodinated flavone derivatives were designed and synthesized. The binding affinities of flavone derivatives for A beta aggregates varied from 13 to 77 nM. When in vitro plaque labeling was carried out using post-mortem AD brain sections, all flavones intensely stained not only amyloid plaques but also cerebrovascular amyloids. In biodistribution studies using normal mice, they displayed high brain uptakes ranging from 3.2 to 4.1% ID/g at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.5-1.9% ID/g at 30 min), which is highly desirable for amyloid imaging agents. The results in the study suggest that these classes of radioiodinated flavones may be useful candidates as potential imaging agents for amyloid plaques.
大脑中β-淀粉样蛋白（Aβ）肽聚集体的体内成像可能有助于阿尔茨海默病（AD）的早期检测以及对AD治疗进展和疗效的监测。本研究的目的是开发以黄酮为核心结构的新型淀粉样蛋白成像剂。设计并合成了放射性碘化黄酮衍生物。黄酮衍生物对Aβ聚集体的结合亲和力在13至77 nM之间。使用死后AD脑切片进行体外斑块标记时，所有黄酮不仅能强烈染色淀粉样斑块，还能染色脑血管淀粉样蛋白。在使用正常小鼠的生物分布研究中，它们在注射后2分钟时显示出3.2至4.1% ID/g的高脑摄取量。放射性迅速从脑中清除（30分钟时为0.5至1.9% ID/g），这对于淀粉样蛋白成像剂来说是非常理想的。该研究结果表明，这些类别的放射性碘化黄酮可能是作为淀粉样斑块潜在成像剂的有用候选物。
