Abstract
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.
Highlights
In the United States, melanoma, a cancer with growing frequency, is expected to affect roughly 96,480 new patients in 2019 with over 7230 projected to succumb to the disease [1]
As recently as 2011, treatment options for late stage melanoma were very limited and only offered small improvements, upon the approval of vemurafenib, a B-RAF inhibitor, initial results were promising in patients positive for the mutated B-RAF protein, roughly 40–60% of people diagnosed with melanoma [4]
We have recently reported on the structure and preliminary encouraging in vivo evaluation of a murine IgG to melanin as a delivery vehicle in radioimmunotherapy (RIT) of melanoma
Summary
In the United States, melanoma, a cancer with growing frequency, is expected to affect roughly 96,480 new patients in 2019 with over 7230 projected to succumb to the disease [1]. At the pre-determined time points of 1, 2, 24, 48, and 72 h post-injection of the radiolabeled antibody the mice were humanely sacrificed, their major organs, blood, and tumors removed, weighted, and counted in Perkin Elmer 2470 Automatic Gamma Counter.
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