title: Synthesis, radiolabeling and preliminary in vivo evaluation of multimodal radiotracers for PET imaging and targeted radionuclide therapy of pigmented melanoma.
abstract: Melanin pigment represents an attractive target to address specific treatment to melanoma cells, such as cytotoxic radionuclides. However, less than half of the patients have pigmented metastases. Hence, specific marker is required to stratify this patient population before proceeding with melanin-targeted radionuclide therapy. In such a context, we developed fluorinated analogues of a previously studied melanin-targeting ligand, N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide (ICF01012). These latter can be labeled either with (18)F or (131)I/(125)I for positron emission tomography imaging (melanin-positive patient selection) and targeted radionuclide therapy purposes. Here we describe the syntheses, radiosyntheses and preclinical evaluations on melanoma-bearing mice model of several iodo- and fluoro(hetero)aromatic derivatives of the ICF01012 scaffold. After preliminary planar gamma scintigraphic and positron emission tomography imaging evaluations, [(125)I]- and [(18)F]-N-[2-(diethylamino)ethyl]-4-fluoro-3-iodobenzamides ([(125)I]4, [(18)F]4) were found to be chemically and biologically stable with quite similar tumor uptakes at 1 h p.i. (9.7 ± 2.6% ID/g and 6.8 ± 1.9% ID/g, respectively).
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Emilie M F
authors: EM
authors: Billaud
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Aurélie
authors: A
authors: Maisonial-Besset
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Latifa
authors: L
authors: Rbah-Vidal
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Aurélien
authors: A
authors: Vidal
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Sophie
authors: S
authors: Besse
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Jean-Baptiste
authors: JB
authors: Béquignat
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Caroline
authors: C
authors: Decombat
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Françoise
authors: F
authors: Degoul
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Laurent
authors: L
authors: Audin
authors: Laboratoires CYCLOPHARMA, Biopôle Clermont-Limagne, Saint-Beauzire F-63360, France.
authors: Jean-Bernard
authors: JB
authors: Deloye
authors: CEA, Service Hospitalier Frédéric Joliot, F-91406 Orsay, France.
authors: Frédéric
authors: F
authors: Dollé
authors: CEA, Service Hospitalier Frédéric Joliot, F-91406 Orsay, France.
authors: Bertrand
authors: B
authors: Kuhnast
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Jean-Claude
authors: JC
authors: Madelmont
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Sébastien
authors: S
authors: Tarrit
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Marie-Josèphe
authors: MJ
authors: Galmier
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Michèle
authors: M
authors: Borel
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Philippe
authors: P
authors: Auzeloux
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France.
authors: Elisabeth
authors: E
authors: Miot-Noirault
authors: Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, F-63000 Clermont-Ferrand, France; Inserm, U 990, F-63000 Clermont-Ferrand, France; Centre Jean Perrin, F-63011 Clermont-Ferrand, France. Electronic address: j-michel.chezal@udamail.fr.
authors: Jean-Michel
authors: JM
authors: Chezal
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D008297:Male; D008546:Melanoma, Experimental / Q000175:diagnosis* / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers
chemical_list: D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D011849:Radioactive Tracers
keywords: Fluorine-18; In vivo screening; Iodine-125; Melanoma; PET imaging