Chen, Kuo-TingNguyen, KevinIeritano, ChristianGao, FengSeimbille, Yann2020-11-022020-11-022018-12-21https://doi.org/10.3390/molecules24010023http://hdl.handle.net/10012/16489We herein describe a flexible synthesis of a small library of 68Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (1–3) 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 (8 and 9) yielded six new 68Ga-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 68Ga-labeled imaging agents for tumor hypoxia.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/carbonic anhydrase IX68Ga-labelingclick reactioncompound libraryArticle