68Ga-DOTA-GGNle-CycMSHhex targets the melanocortin-1 receptor for melanoma imaging.

⁶⁸Ga-DOTA-GGNle-CycMSH_hex, a radiolabeled melanocortin-1 receptor–targeting imaging probe, detects melanoma in first-in-human testing. Visualizing the target: Metastatic melanoma (skin cancer) has a high mortality rate. Yang et al. designed radiolabeled positron emission tomography and fluorescent imaging probes targeting melanocortin-1 receptor, which is overexpressed in melanoma cells. The probes detected melanoma cells in vitro, in xenografts and mouse models, and in metastases in two patients with melanoma. These results suggest that melanocortin-1 receptor-targeting probes may be useful 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 ⁶⁸Ga-DOTA-GGNle-CycMSH_hex and Cy5.5-GGNle-CycMSH_hex using murine and human melanoma cells, and murine and xenografted tumors. ⁶⁸Ga-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. ⁶⁸Ga-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 ⁶⁸Ga-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 ⁶⁸Ga-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. [ABSTRACT FROM AUTHOR]