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 ⁹⁰Y-DOTA-GGNle-CycMSH_hex to facilitate its potential therapeutic application. Materials and Methods: DOTA-GGNle-CycMSH_hex was synthesized and readily labeled with ⁹⁰Y in 0.25 M NH₄Ac-buffered solution to generate ⁹⁰Y-DOTA-GGNle-CycMSH_hex. The specific receptor binding, internalization, and efflux of ⁹⁰Y-DOTA-GGNle-CycMSH_hex were determined on B16/F10 murine melanoma cells. The biodistribution property of ⁹⁰Y-DOTA-GGNle-CycMSH_hex was examined on B16/F10 melanoma-bearing C57 mice. Results: ⁹⁰Y-DOTA-GGNle-CycMSH_hex displayed receptor-specific binding, rapid internalization, and prolonged efflux on B16/F10 melanoma cells. ⁹⁰Y-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: ⁹⁰Y-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 ⁹⁰Y-DOTA-GGNle-CycMSH_hex warranted its evaluation for melanoma therapy in future studies.