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

The syntheses of new nitroimidazole compounds using silicon-[F-18]fluorine chemistry for the potential detection of tumor hypoxia are described. [F-18]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/mu mol, however these compounds ([F-18]7 and [F-18]11) were not stable in plasma. Phenyldi-tert-butyl compounds were labeled in 70% yield with a specific activity of 3 GBq/mu mol by isotopic exchange, or in 81% yield by fluorolysis of siloxanes with a specific activity of 45 GBq/mu mol. The labeled compound [F-18]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 [F-18]18 is suitable for further in vivo assessments. (C) 2013 Elsevier Ltd. All rights reserved.