Anti-melanoma efficacy of internal radionuclide therapy in relation to melanin target distribution

Summary 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 [131I]ICF01012 radiotherapy in vitro and in vivo in relation to melanogenesis using human melanoma models. [125I]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 [131I]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 131I‐labelled iodoquinoxaline for effective treatment of melanoma.