title: Melanocortin-1 receptor-targeting with radiolabeled cyclic α-melanocyte-stimulating hormone analogs for melanoma imaging.
abstract: 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.
authors.affiliation: Unidade de Ciências Químicas e Radiofarmacêuticas, ITN, Estrada Nacional 10, 2686-953 Sacavém, Portugal. paular@itn.pt
authors.forename: Paula D
authors.initials: PD
authors.lastname: Raposinho
authors.forename: João D G
authors.initials: JD
authors.lastname: Correia
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Oliveira
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D057054:Molecular Imaging; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011485:Protein Binding; D044102:Receptor, Melanocortin, Type 1 / Q000737:chemistry / Q000378:metabolism*; D000521:alpha-MSH / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D010456:Peptides, Cyclic; D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH