title: Synthesis, radiofluorination, and in vivo evaluation of novel fluorinated and iodinated radiotracers for PET imaging and targeted radionuclide therapy of melanoma.
abstract: 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, [(18)F]8 emerged as the most promising compound. [(18)F]8 was obtained by a fully automated radiosynthesis process within 57 min with an overall radiochemical yield of 21%, decay-corrected. PET imaging of [(18)F]8 demonstrated very encouraging results as early as 1 h postinjection with high tumor uptake (14.33% ± 2.11% ID/g), high contrast (11.04 ± 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.
authors.affiliation: Clermont Université, Université d'Auvergne , Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France.
authors.forename: Emilie M F
authors.initials: EM
authors.lastname: Billaud
authors.forename: Latifa
authors.initials: L
authors.lastname: Rbah-Vidal
authors.forename: Aurélien
authors.initials: A
authors.lastname: Vidal
authors.forename: Sophie
authors.initials: S
authors.lastname: Besse
authors.forename: Sébastien
authors.initials: S
authors.lastname: Tarrit
authors.forename: Serge
authors.initials: S
authors.lastname: Askienazy
authors.forename: Aurélie
authors.initials: A
authors.lastname: Maisonial
authors.forename: Nicole
authors.initials: N
authors.lastname: Moins
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Madelmont
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.forename: Philippe
authors.initials: P
authors.lastname: Auzeloux
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011810:Quinoxalines / Q000138:chemical synthesis / Q000627:therapeutic use*; D011849:Radioactive Tracers; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: C587001:N-(12-ethyl-1-fluoro-3,6,9-trioxa-12-azatetradecan-14-yl)-6-iodoquinoxaline-2-carboxamide; D011810:Quinoxalines; D011849:Radioactive Tracers