Tc(CO)-((S-Pyridin-2-ylmethyl)-Cys)-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH

Malignant melanoma is the deadliest form of skin cancer (1). Early and accurate diagnosis is necessary for surgery and successful treatment (2). The melanocortin (MC) (3) system is a neuropeptide network of the skin, and it is involved in pigmentation regulation, cortisol production, and many other physiological processes (4). Most cutaneous cell types express MC receptors, proopiomelanocortin (POMC), and prohormone convertases in addition to MCs. However, these receptors have been found to be overexpressed in melanoma cells. There are five MC receptors (MC1R to MC5R), which belong to the G-protein−coupled receptor superfamily (5). Melanotropin-stimulating hormones (α-, β-, and γ-MSH) are derived from POMC by the proteolytic action of prohormone convertases. α-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH), produced by the brain and pituitary gland, is a tridecapeptide (13 amino acids) and is the most potent melanotropic peptide (6) in the regulation of skin pigmentation MC1R. Although positron emission tomography (PET) imaging with [F]fluoro-2-deoxy-2-d-glucose ([F]FDG) is effective in the detection of melanoma, it is not melanoma-specific and some melanoma cells do not take up [F]FDG (7, 8). [F]FDG has been approved for cancer imaging by the United States Food and Drug Administration. Radiolabeled α-MSH peptide analogs have been shown to specifically bind to MC1R that is overexpressed on human and mouse melanoma cells (7, 9-12). Jiang et al. (13) prepared a linear α-MSH analog (Cys-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH, (NAPamide)) containing a S-pyridin-2-ylmethyl moiety (peptide 6) at the N-terminus Cys for radiolabeling with Tc. Tc(CO)(S-Pyridin-2-ylmethyl)-Cys)-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH ([Tc(CO)(,,-6)]) was evaluated in mice bearing melanoma tumors as a potential agent for use with single-photon emission computed tomography (SPECT) imaging to target melanoma.