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

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

  • J Labelled Comp Radiopharm. 2024 Feb;67(2):59-66. doi: 10.1002/jlcr.4081.
Anna Marešová 1,  Michal Jurášek 1,  Pavel B Drašar 1,  Bohumil Dolenský 2,  Elena A Prokudina 1,  Vladimir Shalgunov 3 4,  Matthias M Herth 3,  Paul Cumming 5 6,  Alexander Popkov 7 8
Affiliations

Affiliations

  • 1 Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Praha 6, Czech Republic.
  • 2 Department of Analytical Chemistry, University of Chemistry and Technology Prague, Praha 6, Czech Republic.
  • 3 Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
  • 4 PET and Cyclotron Unit, Copenhagen University Hospital, Copenhagen, Denmark.
  • 5 Department of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
  • 6 School of Psychology and Counselling, Queensland University of Technology, Kevin Grove, Queensland, Australia.
  • 7 Institute of Organic Chemistry, Johannes Kepler University, Linz, Austria.
  • 8 Samo Biomedical Centre, Pardubice, Czech Republic.
PMID: 38171540 DOI: 10.1002/jlcr.4081
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 [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.

Keywords

FTC-146; PET; [18F]FTC-146; chloride leaving group, fluorine-18; non-activated; precursor; radiopharmaceutical; radiosynthesis; σ-1 receptor.

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