[F]FB-(Ac-NIe-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH)

[F]FB-(Ac-NIe-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH) ([F]FB-NAPamide) is a radioligand developed as a positron emission tomography (PET) imaging probe for primary and metastatic melanoma (1). [F]FB-NAPamide is an α-melanocyte−stimulating hormone (MSH) peptide labeled with F, a positron emitter with a physical half-life () of 109.7 min. Malignant melanoma is the sixth most common cancer in the United States (2). Early diagnosis and prompt surgical removal comprise the best approach for a possible cure (3). The melanocortin (MC) system is the best characterized 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, and they also release MCs. Five MC receptors (MC-1 to MC-5) have been cloned and characterized as receptors that belong to the G-protein−coupled receptors superfamily. MSHs (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) is a peptide of 13 amino acids and is the most potent naturally occurring melanotropic peptide (5). The biological effects of α-MSH are mediated MC receptors. Although 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 (6, 7). Radiolabeled α-MSH peptide analogs have been shown to specifically bind to MC-1 receptors that are overexpressed on human and mouse melanoma cells (6, 8-11). Some studies have successfully used 1,4,7,10-tetraazacyclododecane-,,,-tetraacetic acid (DOTA) coupled to the α-MSH peptide analogs for radiolabeling. These α-MSH derivatives (DOTA-α-MSHs) can be labeled with a variety of radionuclides (6). To improve the pharmacokinetics of these radiolabeled peptides, a number of different α-MSH analogs have been designed (12, 13). Froidevaux et al (12). showed that the kidney uptake of a short linear DOTA-α-MSH analog (DOTA-NAPamide) could be considerably reduced by neutralizing the charge of the Lys residue. Cheng et al. (14) synthesized Cu-DOTA-NAPamide and showed that it is a promising molecular probe for PET imaging of melanomas positive for α-MSH receptors. However, the Cu-labeled peptide also showed relatively high radioactivity levels in the liver and kidneys. Cheng et al. (1) suggested that this high hepatobiliary radioactivity accumulation was primarily caused by transchelation of Cu from the radiolabeled peptide . They further proposed that the NAPamide peptide labeled with F might have the advantage of fast radioactivity clearance from normal tissues. Cheng et al. (1) reported the successful preparation of [F]FB-NAPamide by conjugation with -succinimidyl-4-[F]fluorobenzoate ([F]SFB) through the lysine side-chain є-amino group.