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

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• 作者：Yoann Joyard^a ; ^b ; Rabah Azzouz^a ; Laurent Bischoff^a ; Cyril Papamica&euml ; l^a ; Daniel Labar^c ; Anne Bol^c ; Vanessa Bol^c ; Pierre Vera^b ; Vincent Gré ; goire^c ; Vincent Levacher^a ; Pierre Bohn^b ; ^{pierre.bohn@chb.unicancer.fr}
• 关键词：Fluorine-18 ; Fluorosilane ; PET ; Hypoxia
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 July, 2013
• 年：2013
• 卷：21
• 期：13
• 页码：3680-3688
• 全文大小：837 K

文摘

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