Melanoma is a
cancer with increasing incidence and there is a need for alternatives to
immunotherapy within effective approaches to treatment of metastatic
melanoma. We performed comparative
radioimmunotherapy (RIT) of experimental B16-F10
melanoma with novel humanized
IgG to
melanin h8C3 labeled with a beta emitter, 177Lu, and an alpha-emitter, 213Bi, as well as biodistribution, microSPECT/CT imaging, and mouse and human dosimetry calculations. microSPECT/CT imaging showed that a humanized antibody that targets "free"
melanin in the tumor microenvironment had high
tumor uptake in B16F10 murine
melanoma in C57Bl/6 mice, with little to no uptake in naturally melanized tissues. Extrapolation of the mouse dosimetry data to an adult human demonstrated that doses delivered to major organs and the whole body by 177Lu-h8C3 would be approximately two times higher than those delivered by 213Bi-h8C3, while the doses to the
tumor would be almost similar. RIT results indicated that 213Bi-h8C3 was more effective in slowing down the
tumor growth than 177Lu-h8C3, while both radiolabeled
antibodies did not produce significant hematologic or systemic side effects. We concluded that h8C3 antibody labeled with 213Bi is a promising
reagent for translation into a clinical trial in patients with metastatic
melanoma.