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.

在这项研究中，为了开发针对GSK-3BETA的核医学成像探针，我们新设计和合成了基于马来酰亚胺支架（[125i] 7）的125i标记化合物。在正常小鼠的生物分布研究中，[125i] 7显示出足够的大脑摄取，足以使GSK-3BETA体内成像。此外，在使用GSK-3BETA的体外结合测定中，化合物7对GSK-3Beta的结合亲和力比以前作为GSK-3BETA抑制剂报道的Indirubin-3'-Oxime更高。这项研究中的这些结果表明，通过进一步优化化学结构来开发针对GSK-3BETA的核医学成像探针是可行的。

项目成果

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

^<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.