n-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide and Skin-Neoplasms

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.

Topics: Animals; Cell Line, Tumor; Humans; Iodine Radioisotopes; Male; Melanins; Melanoma; Melanosomes; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplasm Transplantation; Pigmentation; Quinoxalines; Skin Neoplasms; Transplantation, Heterologous; Tumor Protein, Translationally-Controlled 1