Synthesis, Radiofluorination, and in Vivo Evaluation of Novel Fluorinated and Iodinated Radiotracers for PET Imaging and Targeted Radionuclide Therapy of Melanoma

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• 作者：Emilie M. F. Billaud ; Latifa Rbah-Vidal ; Aur茅lien Vidal ; Sophie Besse ; S茅bastien Tarrit ; Serge Askienazy ; Aur茅lie Maisonial ; Nicole Moins ; Jean-Claude Madelmont ; Elisabeth Miot-Noirault ; Jean-Michel Chezal ; Philippe Auzeloux
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：November 14, 2013
• 年：2013
• 卷：56
• 期：21
• 页码：8455-8467
• 全文大小：470K
• 年卷期：v.56,no.21(November 14, 2013)
• ISSN：1520-4804

文摘

Our project deals with a multimodal approach using a single fluorinated and iodinated melanin-targeting structure and offering both imaging (positron emission tomography (PET)/fluorine-18) and treatment (targeted radionuclide therapy/iodine-131) of melanoma. Six 6-iodoquinoxaline-2-carboxamide derivatives with various side chains bearing fluorine were synthesized and radiofluorinated, and their in vivo biodistribution was studied by PET imaging in B16Bl6 primary melanoma-bearing mice. Among this series, [¹⁸F]8 emerged as the most promising compound. [¹⁸F]8 was obtained by a fully automated radiosynthesis process within 57 min with an overall radiochemical yield of 21%, decay-corrected. PET imaging of [¹⁸F]8 demonstrated very encouraging results as early as 1 h postinjection with high tumor uptake (14.33% 卤 2.11% ID/g), high contrast (11.04 卤 2.87 tumor-to-muscle ratio), and favorable clearance properties. These results, associated with the previously reported pharmacokinetic properties and dosimetry of 8, make it a potential agent for both PET imaging and targeted radionuclide therapy of melanoma.