68Ga-DOTA-GGNle-CycMSHhextargets 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 of68Ga-DOTA-GGNle-CycMSHhexand Cy5.5-GGNle-CycMSHhexusing murine and human melanoma cells, and murine and xenografted tumors.68Ga-DOTA-GGNle-CycMSHhexwas used first in human as an imaging probe to evaluate the possibility of radionuclide therapy in patients with advanced-stage melanoma.68Ga-DOTA-GGNle-CycMSHhexand Cy5.5-GGNle-CycMSHhexdisplayed 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 using68Ga-DOTA-GGNle-CycMSHhex. 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 of68Ga-DOTA-GGNle-CycMSHhexas an MC1R-targeting melanoma imaging probe and underscoring the need to develop MC1R-targeting therapeutic agents for treating patients with metastatic melanoma.