Synthesis of new 18F-radiolabeled silicon-based nitroimidazole compounds

Bioorg Med Chem. 2013 Jul 1;21(13):3680-8. doi: 10.1016/j.bmc.2013.04.029. Epub 2013 Apr 22.

Abstract

The syntheses of new nitroimidazole compounds using silicon-[(18)F]fluorine chemistry for the potential detection of tumor hypoxia are described. [(18)F]silicon-based compounds were synthesized by coupling 2-nitroimidazole with silyldinaphtyl or silylphenyldi-tert-butyl groups and labeled by fluorolysis or isotopic exchange. Dinaphtyl compounds (6, 10) were labeled in 56-71% yield with a specific activity of 45 GBq/μmol, however these compounds ([(18)F]7 and [(18)F]11) were not stable in plasma. Phenyldi-tert-butyl compounds were labeled in 70% yield with a specific activity of 3 GBq/μmol by isotopic exchange, or in 81% yield by fluorolysis of siloxanes with a specific activity of 45 GBq/μmol. The labeled compound [(18)F]18 was stable in plasma and excreted by the liver and kidneys in vivo. In conclusion, the fluorosilylphenyldi-tert-butyl (SiFA) group is more stable in plasma than fluorosilyldiphenyl moiety. Thus, compound [(18)F]18 is suitable for further in vivo assessments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / metabolism
  • Humans
  • Hypoxia / diagnosis
  • Nitroimidazoles / chemical synthesis
  • Nitroimidazoles / chemistry*
  • Nitroimidazoles / metabolism
  • Positron-Emission Tomography / methods
  • Rats
  • Rats, Wistar
  • Silicon / chemistry*
  • Silicon / metabolism
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • Nitroimidazoles
  • Silicon