Leung Kam
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
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.
恶性黑色素瘤是最致命的皮肤癌形式（1）。早期准确诊断对于手术和成功治疗至关重要（2）。黑皮质素（MC）（3）系统是皮肤的一种神经肽网络，参与色素沉着调节、皮质醇生成及许多其他生理过程（4）。除了MCs外，大多数皮肤细胞类型还表达MC受体、阿片促黑皮质素原（POMC）和激素原转化酶。然而，已发现这些受体在黑色素瘤细胞中过表达。有五种MC受体（MC1R至MC5R），它们属于G蛋白偶联受体超家族（5）。促黑素（α-、β-和γ-MSH）是由激素原转化酶的蛋白水解作用从POMC衍生而来。由脑和垂体产生的α-MSH（Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH）是一种十三肽（13个氨基酸），是调节皮肤色素沉着中最有效的促黑素肽（6）。尽管用[F]氟-2-脱氧-2-D-葡萄糖（[F]FDG）进行正电子发射断层扫描（PET）成像在检测黑色素瘤方面有效，但它并非黑色素瘤特异性的，且一些黑色素瘤细胞不摄取[F]FDG（7,8）。[F]FDG已被美国食品药品监督管理局批准用于癌症成像。放射性标记的α-MSH肽类似物已被证明能特异性结合在人和小鼠黑色素瘤细胞上过表达的MC1R（7,9 - 12）。Jiang等人（13）制备了一种线性α-MSH类似物（Cys-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH，（NAPamide）），其N端Cys处含有一个S-吡啶-2-基甲基部分（肽6）用于用Tc进行放射性标记。Tc(CO)(S-吡啶-2-基甲基)-Cys)-Nle-Asp-His-d-Phe-Arg-Trp-Gly-Lys-NH（[Tc(CO)(,, - 6)]）在荷黑色素瘤肿瘤的小鼠中作为用于单光子发射计算机断层扫描（SPECT）成像靶向黑色素瘤的潜在药物进行了评估。
