We 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.

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Keywords 68Ga-labeling, carbonic anhydrase IX, click reaction, compound library
Persistent URL dx.doi.org/10.3390/molecules24010023, hdl.handle.net/1765/113528
Journal Molecules (Basel, Switzerland)
Chen, K.-T. (Kuo-Ting), Nguyen, K. (Kevin), Ieritano, C. (Christian), Gao, F. (Feng), & Seimbille, Y. (Yann). (2018). A Flexible Synthesis of 68Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction. Molecules (Basel, Switzerland), 24(1). doi:10.3390/molecules24010023