Development of nuclear medical imaging probes targeting GSK-3beta for early diagnosis of tauopathy

开发针对 GSK-3beta 的核医学成像探针，用于 tau 蛋白病的早期诊断

• 批准号: 24659564
• 负责人: SAJI Hideo
• 金额: $ 2.41万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659564/
• 关键词: タウオパチー; GSK-3β; 認知症; イメージング; 診断

In this study, to develop nuclear medical imaging probes targeting GSK-3beta, we newly designed and synthesized 125I-labeled compound based on maleimide scaffold ([125I]7). In biodistribution study in normal mice, [125I]7 showed high brain uptake sufficient for in vivo imaging of GSK-3beta. In addition, in in vitro binding assay using GSK-3beta, compound 7 displayed higher binding affinity for GSK-3beta than indirubin-3'-oxime reported previously as a GSK-3beta inhibitor. These results in this study suggest that it will be feasible to develop nuclear medical imaging probes targeting GSK-3beta by further optimizing the chemical structure.

本研究以GSK-3 β为靶点，设计并合成了125 I标记的马来酰亚胺（[125 I]7）为骨架的化合物。在正常小鼠的生物分布研究中，[125 I]7显示出足够用于GSK-3 β体内成像的高脑摄取。此外，在使用GSK-3 β的体外结合测定中，化合物7显示出比先前作为GSK-3 β抑制剂报道的靛玉红-3 '-肟更高的GSK-3 β结合亲和力。本研究结果表明，通过进一步优化GSK-3 β的化学结构，开发靶向GSK-3 β的核医学成像探针是可行的。

项目成果

(18)F-labeled phenyldiazenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains.

• DOI: 10.1021/ml200230e
• 发表时间: 2012-01
• 期刊: ACS medicinal chemistry letters
• 影响因子: 4.2
• 作者: K. Matsumura;M. Ono;H. Kimura;M. Ueda;Y. Nakamoto;K. Togashi;Y. Okamoto;M. Ihara;R. Takahashi;H. Saji

^<18>F-Labeled phenyl benzothiazole for in vivo imaging of neurofibrillary tangles in Alzheimer's disease brains

^<18>F-标记的苯基苯并噻唑用于阿尔茨海默病大脑中神经原纤维缠结的体内成像

• 发表时间: 2012
• 期刊: ACS Medicinal Chemistry Letter
• 作者: Matsumura K;Ono M;Kimura H;Ueda M;Nakamoto Y;Togashi K;Okamoto Y;Ihara M;Takahashi R;Saji H.
• 通讯作者: Saji H.

Synthesis and biological evaluation of novel styryl benzimidazole derivatives as probes for imaging of neurofibrillary tangles in Alzheimer's disease

• DOI: 10.1016/j.bmc.2013.02.054
• 发表时间: 2013-06-01
• 期刊: BIOORGANIC & MEDICINAL CHEMISTRY
• 影响因子: 3.5
• 作者: Matsumura, Kenji;Ono, Masahiro;Saji, Hideo
• 通讯作者: Saji, Hideo