[131I] ICF01012, a potential agent for targeted radionuclide therapy of melanoma

Objectives In recent years, there has been a dramatic worldwide increase in incidence of melanoma. Although disease is frequently curable by local surgery, metastatic melanoma is inherently resistant to most treatments. Targeted radionuclide therapy could be an efficient alternative. At our institution, a class of iodobenzamides has been developed as potent melanoma-seeking agents. A quinoxaline derivative (ICF01012) was selected for its high specific and long-lasting uptake in tumor with rapid clearance from non-target organs providing suitable dosimetry parameters. Aim of the study is to investigate the efficacy of [¹³¹I]ICF01012 for melanoma radionuclide therapy.

Methods [¹³¹I]ICF01012 was administered i.v into C57BL6 mice bearing the nonmetastatic B16F0 or metastatic B16bl6 cell lines grafted s.c.

Results Treatment drastically suppressed the growth of both B16F0 and B16bl6 tumors whereas treatment with [¹³¹I]NaI or with unlabeled ICF01012was without significant effect. The tumor doubling time after [¹³¹I]ICF01012 treatment was significantly increased (+147 to +164%). Histology analysis of residual treated-tumors revealed an increased melanin content, a decreased number of mitoses and a defect in microvascularization suggesting a loss of aggressiveness.Moreover, with B16bl6 model, 55% of the untreated mice had lung metastases whereas no metastase was counted on treated group.

Conclusions Our data demonstrated a strong anti-tumoral effect of [¹³¹I]ICF01012 as radionuclide therapeutic agent on two in vivo melanoma models whatever their dissemination profiles. Further studies will attempt to optimize the therapy protocol by increasing the balance between the anti-tumoral effect and safety on non-target organs.