Radiolabeled Alpha-Melanocyte Stimulating Hormone Derivatives for Development of Malignant Melanoma Imaging Agents

Abstract

Malignant melanoma is a very aggressive metastatic skin cancer with a high mortality rate. Thus, an accurate early diagnosis of metastatic melanoma is the best treatment for patients. The melanocortin-1 receptor (MC1R) is overexpressed in human melanoma cells but exhibits low expression in normal tissues. This charac teristic makes it an attractive target for detection of malignant melanoma. Alpha-melanocyte stimulating hormone (α-MSH), one of the endogenous ligands of MC1R, binds to MC1R through its core sequence. However, it is challenging to utilize the native structure of α-MSH, so researchers have found that stabilizing it through cyclization can offer more favorable outcomes in both preclinical and clinical studies. This review introduces the development of radionuclide-labeled α-MSH derivatives that selectively bind to MC1R, a malignant melanoma-specific target. It also explains on the development of cyclized α-MSH derivatives and the results of biological evaluations related to renal uptake.