Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC V6T2A3, Canada.
Molecules. 2018 Dec 21;24(1):23. doi: 10.3390/molecules24010023.
We herein describe a flexible synthesis of a small library of Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (⁻) were successfully synthesized and labeled with the positron emitter gallium-68. Cross-ligation between the pre-labeled bifunctional chelators (BFCs) and the 1,2-aminothiol-acetazolamide derivatives ( and ) yielded six new Ga-labeled CAIX ligands with high radiochemical yields. The click reaction conditions were optimized to improve the reaction rate for applications with short half-life radionuclides. Overall, our methodology allows for a simple and efficient radiosynthetic route to produce a variety of Ga-labeled imaging agents for tumor hypoxia.
我们在此描述了一种通过正交的 2-氰基苯并噻唑（CBT）/1,2-氨硫醇点击反应来灵活合成 Ga 标记的 CAIX 靶向小分子文库的方法。成功合成了三个新型 CBT 功能化螯合剂（⁻），并用正电子发射体镓-68 进行了标记。预标记的双功能螯合剂（BFC）与 1,2-氨硫醇-乙酰唑胺衍生物（和）之间的交叉连接生成了六种新的 Ga 标记的 CAIX 配体，具有高放射化学产率。点击反应条件进行了优化，以提高半衰期短的放射性核素的反应速率。总的来说，我们的方法为生产用于肿瘤乏氧成像的各种 Ga 标记的成像剂提供了一种简单高效的放射合成途径。
