Ga-68-DOTA-GGNle-CycMSH(hex) targets the melanocortin-1 receptor for melanoma imaging

Melanocortin-1 receptor (MC1R) is a molecular target for melanoma imaging and therapy because of its overexpression on rodent and human melanoma cells. Here, we evaluated the MC1R targeting and specificity of Ga-68-DOTA-GGNle-CycMSH(hex) and Cy5.5-GGNle-CycMSH(hex) using murine and human melanoma cells, and murine and xenografted tumors. Ga-68-DOTA-GGNle-CycMSH(hex) was used first in human as an imaging probe to evaluate the possibility of radionuclide therapy in patients with advanced-stage melanoma. Ga-68-DOTA-GGNle-CycMSH(hex) and Cy5.5-GGNle-CycMSH(hex) displayed MC1R-specific targeting properties in murine and human melanoma cells, as well as in murine melanoma and human melanoma- xenografted tumors. Both B16/F10 and M21 melanoma lesions could be easily imaged by positron emission tomography using Ga-68-DOTA-GGNle-CycMSH(hex). The first-in-human images of melanoma brain metastases in patients demonstrated the clinical relevance of MC1R as a molecular target for melanoma imaging, highlighting the potential of Ga-68-DOTA-GGNle-CycMSH(hex) as an MC1R-targeting melanoma imaging probe and underscoring the need to develop MC1R-targeting therapeutic agents for treating patients with metastatic melanoma.