Design and synthesis of enantiopure 18 F-labelled [18 F]trifluoromethyltryptophan from 2-halotryptophan derivatives via copper(I)-mediated [18 F]trifluoromethylation and evaluation of its in vitro characterization for the serotonergic system imaging

J Labelled Comp Radiopharm. 2019 Jul;62(9):566-579. doi: 10.1002/jlcr.3772. Epub 2019 Jun 24.

Abstract

We synthesized [18 F]trifluoromethyl-l-tryptophan ([18 F]CF3 -l-Trp) using Cu(I)-mediated [18 F]trifluoromethylation to image serotonergic system. Radiochemical yield was 6 ± 1.5% (n = 9), and radiochemical purity was over 99%. The molar activity was 0.44 to 0.76 GBq/μmol. [18 F]CF3 -l-Trp was stable for up to 6 hours in mouse and human sera at 37°C. Protein-binding was 0.26 ± 0.03% and 0.34 ± 0.02% in human and mouse serum at 60 minutes, respectively. In conclusion, enantiopure [18 F]CF3 -l-Trp was synthesized as a feasible imaging agent for the serotonergic system.

Keywords: 5-HT; CF3-l-Trp; amino acid; serotonin; tryptophan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Proteins / metabolism
  • Catalysis
  • Chemistry Techniques, Synthetic
  • Copper / chemistry*
  • Drug Design*
  • Fluorine Radioisotopes / chemistry*
  • Halogenation
  • Humans
  • Isotope Labeling
  • Methylation
  • Mice
  • Molecular Imaging / methods*
  • Radiochemistry
  • Serotonin / metabolism*
  • Stereoisomerism
  • Tryptophan / chemical synthesis*
  • Tryptophan / chemistry*
  • Tryptophan / metabolism

Substances

  • Blood Proteins
  • Fluorine Radioisotopes
  • Serotonin
  • Copper
  • Tryptophan
  • Fluorine-18