Design of silicon-based misonidazole analogues and (18)F-radiolabelling.

Pierre Bohn 1, 2 Abdallah Deyine 1, 2, 3 Rabah Azzouz 3 Laetitia Bailly 3 Catherine Fiol-Petit 3 Laurent Bischoff 3 Corinne Fruit 3 Francis Marsais 3 Pierre Vera 1, 2
1 LITIS - Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes
2 Service de médecine nucléaire [Rouen]
3 AHHBO - Asymétrie, hétérocycles, hétérochimie et bio-organique
Abstract : INTRODUCTION: Development of new (18)F-labeled tracers for positron emission tomography (PET) imaging is increasingly important. Herein, we described the synthesis of silicon analogues of [(18)F]fluoromisonidazole in order to develop new radiolabelled compounds for the detection of tumour hypoxic domain. Their stabilities and their in vivo biodistribution were evaluated. METHODS: (18)F-labeled silicon-based misonidazole analogues were synthesized by alkylating 2-nitroimidazole with alkyloxy-(3-chloropropyl)dialkyl or diarylsilane. These intermediates were labeled with [(18)F]F(-) with a mixture of K(18)F and Kryptofix (K222) in acetonitrile as standard condition. PET imaging was performed using a dedicated small animal PET scanner. RESULTS: (18)F-labeled silicon-based misonidazole analogues were easily synthesized in three steps. The hydrolytic and radiolytic stability of these new fluorosilanes depend on the steric hindrance at the silicon center. Indeed, partial uptake of dimethylfluorosilane [(18)F]2a(1-(3-(Fluorodimethylsilyl)propyl)-2-nitro-1H-imidazole) in tumor hypoxic area was observed but defluorination also appeared. Moreover, PET studies indicated that, owing to its high lipophilicity, the most stable dinaphtylfluorosilane [(18)F]2d is retained mainly by the lungs. CONCLUSION: We have described an efficient and versatile approach for the synthesis of (18)F-labeled, silicon-based misonidazole analogues. PET imaging of one of these compounds revealed that hypoxia could be detected. Controlling the biodistribution of (18)F-labeled silicon-based misonidazole analogues will require additional studies.
Type de document :
Article dans une revue
Nuclear Medicine and Biology, Elsevier, 2009, 36 (8), pp.895-905. 〈10.1016/j.nucmedbio.2009.06.004〉
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http://www.hal.inserm.fr/inserm-00467158
Contributeur : Céline Breton <>
Soumis le : vendredi 26 mars 2010 - 10:19:12
Dernière modification le : mardi 5 juin 2018 - 10:14:25

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LITIS | INC-CNRS | COMUE-NORMANDIE | FNCLCC | BECQUEREL | INSA-ROUEN | UNIROUEN

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Pierre Bohn, Abdallah Deyine, Rabah Azzouz, Laetitia Bailly, Catherine Fiol-Petit, et al.. Design of silicon-based misonidazole analogues and (18)F-radiolabelling.. Nuclear Medicine and Biology, Elsevier, 2009, 36 (8), pp.895-905. 〈10.1016/j.nucmedbio.2009.06.004〉. 〈inserm-00467158〉

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