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 [18 F]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 [18 F]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 SN 2 reaction with 18 F-fluoride. 18 F-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.

Department of Analytical Chemistry University of Chemistry and Technology Prague Praha 6 Czech Republic

Department of Chemistry of Natural Compounds University of Chemistry and Technology Prague Praha 6 Czech Republic

Department of Drug Design and Pharmacology University of Copenhagen Copenhagen Denmark

Department of Nuclear Medicine University Hospital Bern Bern Switzerland

Institute of Organic Chemistry Johannes Kepler University Linz Austria

PET and Cyclotron Unit Copenhagen University Hospital Copenhagen Denmark

Samo Biomedical Centre Pardubice Czech Republic

School of Psychology and Counselling Queensland University of Technology Kevin Grove Queensland Australia

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