title: Synthesis of new 18F-radiolabeled silicon-based nitroimidazole compounds.
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.
authors.affiliation: UMR 6014, COBRA, CNRS, INSA of Rouen and University of Rouen, rue Tesnière, 76130 Mont-Saint-Aignan, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Joyard
authors.forename: Rabah
authors.initials: R
authors.lastname: Azzouz
authors.forename: Laurent
authors.initials: L
authors.lastname: Bischoff
authors.forename: Cyril
authors.initials: C
authors.lastname: Papamicaël
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bol
authors.forename: Pierre
authors.initials: P
authors.lastname: Vera
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.forename: Vincent
authors.initials: V
authors.lastname: Levacher
authors.forename: Pierre
authors.initials: P
authors.lastname: Bohn
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012825:Silicon / Q000737:chemistry* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D009593:Nitroimidazoles; D012825:Silicon