title: Anti-melanoma efficacy of internal radionuclide therapy in relation to melanin target distribution.
abstract: Targeted internal radionuclide therapy (TRT) could be an efficient, specific way to treat disseminated melanoma. Based on a previous pharmacomodulation study, we selected a quinoxaline-derived molecule (ICF01012) for its melanin specificity and kinetic properties suitable for TRT. Here, we determined the efficacy of [(131)I]ICF01012 radiotherapy in vitro and in vivo in relation to melanogenesis using human melanoma models. [(125)I]ICF01012 uptake was first assessed in relation to melanin content. We found that melanin distribution in different models was representative of pathology seen in human tumours: melanin content was high in the extracellular space of SKMel3 tumours, and accumulated primarily in melanophages in M4Beu tumours. Targeted [(131)I]ICF01012 radiotherapy had a strong anti-tumoural efficacy in pigmented versus unpigmented tumours, regardless of target distribution and content. This study supports the use of melanin targeting with (131)I-labelled iodoquinoxaline for effective treatment of melanoma.
authors.affiliation: UMR 990 INSERM/UdA-Imagerie Moléculaire et Thérapie vectorisée, Clermont-Ferrand, France. mathilde.bonnet@inserm.fr
authors.forename: M
authors.initials: M
authors.lastname: Bonnet
authors.forename: F
authors.initials: F
authors.lastname: Mishellany
authors.forename: J
authors.initials: J
authors.lastname: Papon
authors.forename: A
authors.initials: A
authors.lastname: Cayre
authors.forename: F
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: J C
authors.initials: JC
authors.lastname: Madelmont
authors.forename: E
authors.initials: E
authors.lastname: Miot-Noirault
authors.forename: J M
authors.initials: JM
authors.lastname: Chezal
authors.forename: N
authors.initials: N
authors.lastname: Moins
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D020460:Melanosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010858:Pigmentation; D011810:Quinoxalines / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D014183:Transplantation, Heterologous; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D007457:Iodine Radioisotopes; D008543:Melanins; C530303:N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide; D011810:Quinoxalines; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1