A facile synthesis of precursor for the -1 receptor PET radioligand [¹⁸F]FTC-146 and its radiofluorination

The sigma-1 receptor is a non-opioid transmembrane protein involved in various human pathologies including neurodegenerative diseases, inflammation, and cancer. The previously published ligand [F-18]FTC-146 is among the most promising tools for sigma-1 molecular imaging by positron emission tomography (PET), with a potential for application in clinical diagnostics and research. However, the published six- or four-step synthesis of the tosyl ester precursor for its radiosynthesis is complicated and time-consuming. Herein, we present a simple one-step precursor synthesis followed by a one-step fluorine-18 labeling procedure that streamlines the preparation of [F-18]FTC-146. Instead of a tosyl-based precursor, we developed a one-step synthesis of the precursor analog AM-16 containing a chloride leaving group for the S(N)2 reaction with F-18-fluoride. F-18-fluorination of AM-16 led to a moderate decay-corrected radiochemical yield (RCY = 7.5%) with molar activity (A(m)) of 45.9 GBq/mu mol. Further optimization of this procedure should enable routine radiopharmaceutical production of this promising PET tracer.