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: M Bonnet, F Mishellany, J Papon, A Cayre, F Penault-Llorca, J C Madelmont, E Miot-Noirault, J M Chezal, N Moins
• Journal: Pigment cell & melanoma research (Pigment Cell Melanoma Res) Vol. 23 Issue 5 Pg. e1-11 (Oct 2010) ISSN: 1755-148X [Electronic] England
• PMID: 20444199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Iodine Radioisotopes
• Melanins
• N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide
• Quinoxalines
• Tpt1 protein, mouse
• Tumor Protein, Translationally-Controlled 1

Topics

• Animals
• Cell Line, Tumor
• Humans
• Iodine Radioisotopes (therapeutic use)
• Male
• Melanins (metabolism)
• Melanoma (metabolism, pathology, radiotherapy)
• Melanosomes (metabolism, ultrastructure)
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Neoplasm Transplantation
• Pigmentation
• Quinoxalines (therapeutic use)
• Skin Neoplasms (pathology, radiotherapy)
• Transplantation, Heterologous
• Tumor Protein, Translationally-Controlled 1