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

Abstract

The σ‐1 receptor is a non‐opioid transmembrane protein involved in various human pathologies including neurodegenerative diseases, inflammation, and cancer. The previously published ligand [18F]FTC‐146 is among the most promising tools for σ‐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 [18F]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 SN2 reaction with 18F‐fluoride. 18F‐fluorination of AM‐16 led to a moderate decay‐corrected radiochemical yield (RCY = 7.5%) with molar activity (Am) of 45.9 GBq/μmol. Further optimization of this procedure should enable routine radiopharmaceutical production of this promising PET tracer.