Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Bioorg Med Chem Lett. 2012 Sep 1;22(17):5700-3. doi: 10.1016/j.bmcl.2012.06.086. Epub 2012 Jul 1.
This letter describes the synthesis and biological evaluation of a novel series of radioiodinated oxindole (OI) derivatives for detecting neurofibrillary tangles (NFTs) in the brains of patients with Alzheimer's disease (AD). In binding experiments in vitro, 2-oxindole (2-OI) and 3-oxindole (3-OI) derivatives showed affinity for tau aggregates. The 3-OI derivative 14 showed the highest affinity of these derivatives. In biodistribution experiments using normal mice, the OI derivatives displayed good uptake (2.4-2.5%ID/g at 2 min) and clearance from the brain with time (0.6-1.4%ID/g at 30 min). In fluorescence staining experiments using AD brain sections, 14 clearly stained NFTs. 3-OI may serve as a new molecular scaffold for developing novel NFT imaging agents.
这封信描述了一系列新型放射性碘代吲哚（OI）衍生物的合成和生物学评价，用于检测阿尔茨海默病（AD）患者大脑中的神经纤维缠结（NFTs）。在体外结合实验中，2-氧吲哚（2-OI）和 3-氧吲哚（3-OI）衍生物显示出与 tau 聚集物的亲和力。3-OI 衍生物 14 在这些衍生物中表现出最高的亲和力。在使用正常小鼠的生物分布实验中，OI 衍生物显示出良好的摄取（2 分钟时为 2.4-2.5%ID/g）和随时间从大脑清除（30 分钟时为 0.6-1.4%ID/g）。在使用 AD 脑切片的荧光染色实验中，14 清楚地染色了 NFTs。3-OI 可能成为开发新型 NFT 成像剂的新分子支架。
