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. Biopolymers (Pept Sci) 94: 820–829, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com