Ono Masahiro, Watanabe Rumi, Kawashima Hidekazu, Kawai Tomoki, Watanabe Hiroyuki, Haratake Mamoru, Saji Hideo, Nakayama Morio
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Bioorg Med Chem. 2009 Mar 1;17(5):2069-76. doi: 10.1016/j.bmc.2009.01.025. Epub 2009 Jan 20.
In vivo imaging of beta-amyloid (Abeta) aggregates in the brain may lead to early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. The purpose of this study was to develop novel (18)F-labeled amyloid-imaging probes based on flavones as a core structure. Fluoropegylated (FPEG) flavone derivatives were designed and synthesized. The affinity of the derivatives for Abeta aggregates varied from 5 to 321nM. In brain sections of AD model mice, FPEG flavones with the dimethylamino group intensely stained beta-amyloid plaques. In biodistrubution experiments using normal mice, they displayed high uptake in the brain ranging from 2.9 to 4.2%ID/g at 2 min postinjection. The radioactivity washed out from the brain rapidly (1.3-2.0%ID/g at 30 min), which is highly desirable for beta-amyloid imaging agents. FPEG flavones may be potential PET imaging agents for beta-amyloid plaques in Alzheimer's brains.
大脑中β-淀粉样蛋白（Aβ）聚集体的体内成像可能有助于阿尔茨海默病（AD）的早期检测以及对疾病进展和治疗效果的监测。本研究的目的是开发基于黄酮作为核心结构的新型（18）F标记淀粉样蛋白成像探针。设计并合成了氟聚乙二醇化（FPEG）黄酮衍生物。这些衍生物对Aβ聚集体的亲和力在5至321nM之间。在AD模型小鼠的脑切片中，带有二甲氨基的FPEG黄酮强烈地染色β-淀粉样斑块。在使用正常小鼠的生物分布实验中，它们在注射后2分钟时在脑中的摄取量较高，范围为2.9至4.2%ID/g。放射性物质从脑中迅速清除（30分钟时为1.3 - 2.0%ID/g），这对于β-淀粉样蛋白成像剂来说是非常理想的。FPEG黄酮可能是用于阿尔茨海默病大脑中β-淀粉样斑块的潜在正电子发射断层显像（PET）成像剂。
