Melanoma-Targeting Property of Y-90-Labeled Lactam-Cyclized α-Melanocyte-Stimulating Hormone Peptide

Purpose: The purpose of this study was to evaluate melanoma-targeting property of Y-90-DOTA-GGNle-CycMSH(hex) to facilitate its potential therapeutic application. Materials and Methods: DOTA-GGNle-CycMSH(hex) was synthesized and readily labeled with Y-90 in 0.25 M NH4Ac-buffered solution to generate Y-90-DOTA-GGNle-CycMSH(hex). The specific receptor binding, internalization, and efflux of Y-90-DOTA-GGNle-CycMSH(hex) were determined on B16/F10 murine melanoma cells. The biodistribution property of Y-90-DOTA-GGNle-CycMSH(hex) was examined on B16/F10 melanoma-bearing C57 mice. Results: Y-90-DOTA-GGNle-CycMSH(hex) displayed receptor-specific binding, rapid internalization, and prolonged efflux on B16/F10 melanoma cells. Y-90-DOTA-GGNle-CycMSH(hex) exhibited high uptake and prolonged retention in melanoma, and fast urinary clearance on B16/F10 melanoma-bearing C57 mice. The B16/F10 tumor uptake was 20.73% +/- 7.99%, 19.93% +/- 5.73%, 14.8% +/- 4.61%, and 6.69% +/- 1.85% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Conclusions: Y-90-DOTA-GGNle-CycMSH(hex) displayed melanocortin-1 receptor (MC1R) targeting and specificity on B16/F10 melanoma cells and tumors. The favorable melanoma-targeting property and fast urinary clearance of Y-90-DOTA-GGNle-CycMSH(hex) warranted its evaluation for melanoma therapy in future studies.