Melanocortin-1 receptor-targeting with radiolabeled cyclic α-melanocyte-stimulating hormone analogs for melanoma imaging.

Melanoma is a type of skin cancer known for its high aggressiveness, early dissemination of metastases, and poor prognosis once metastasized. Thus, early diagnosis of melanoma is a key issue for increasing patient survival. The overexpression of melanocortin-1 receptors (MC1R) in isolated melanoma cells and melanoma tissues led to the radiolabeling of several linear and cyclic MC analogs for melanoma imaging or therapy. Cyclization of α-melanocyte stimulating hormone (α-MSH) peptides has been successfully used to improve binding affinity and in vivo stability of peptides. Herein, we describe the different peptide cyclization strategies recently reported for radiolabeled α-MSH analogs and discuss how such strategies affect MC1R binding affinity, pharmacokinetic profile, and MC1R-melanoma imaging. This review also highlights how the nature of the radiometal and labeling approach influence those properties. Among the cyclized α-MSH peptides reported, (99m)Tc/(111)In-labeled metal-cyclized and lactam bridge-cyclized peptides displayed the highest melanoma and lowest renal uptake values in B16/F1 melanoma-bearing mice and became the most promising tools to be further explored as potential melanoma imaging probes. 2010 Wiley Periodicals, Inc.