Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability. In this study, we summarized the development and the in vitro and in vivo characteristics of the radiolabeled αMSH analogues, including 99mTc-, 111In-, 67 Ga-, or 125I-labeled αMSH analogues for imaging with single-photon emission computed tomography; 68Ga-, 64Cu-, or 18F-labeled αMSH analogues for imaging with positron emission tomography; and 188Re-, 177Lu-, 90Y-, or 212Pb-labeled αMSH analogues for radionuclide therapy. These radiolabeled αMSH analogues showed promising results with high tumor uptake and rapid normal tissue activity clearance in the preclinical model of B16F1 and B16F10 mouse melanomas. These results highlight the potential of using radiolabeled αMSH analogues in clinical applications for molecular imaging and radionuclide therapy of melanoma.

中文翻译：

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黑素瘤靶向黑皮质素1受体的分子成像和放射性核素治疗。

黑色素瘤是转移晚期的致命疾病，早期诊断和准确的分期仍然是处理黑色素瘤的关键方面。黑素皮质素1受体（MC1 R）在原发性和转移性黑素瘤中过表达，其内源性配体α-黑素细胞刺激激素（αMSH）已被广泛研究用于靶向MC1 R的分子成像和黑素瘤的治疗。天然的αMSH由于体内的低稳定性而不太适合该目的。非天然氨基酸取代基本稳定了肽，而通过内酰胺桥和金属配位的环化进一步提高了结合亲和力和稳定性。在这项研究中，我们总结了放射性标记的αMSH类似物的开发以及体外和体内特征，包括99mTc-，111In-，67 Ga-，或125 I标记的αMSH类似物，用于单光子发射计算机断层扫描成像；用于正电子发射断层显像的68Ga，64Cu或18F标记的αMSH类似物；和188Re-，177Lu-，90Y-或212Pb标记的αMSH类似物用于放射性核素治疗。这些放射性标记的αMSH类似物在B16F1和B16F10小鼠黑素瘤的临床前模型中具有高肿瘤吸收和快速正常组织活性清除的良好前景。这些结果突显了在临床应用中将放射标记的αMSH类似物用于黑素瘤的分子成像和放射性核素治疗的潜力。这些放射性标记的αMSH类似物在B16F1和B16F10小鼠黑素瘤的临床前模型中具有高肿瘤吸收和快速正常组织活性清除的良好前景。这些结果突显了在临床应用中将放射标记的αMSH类似物用于黑素瘤的分子成像和放射性核素治疗的潜力。这些放射性标记的αMSH类似物在B16F1和B16F10小鼠黑素瘤的临床前模型中显示出令人鼓舞的结果，具有较高的肿瘤吸收率和快速的正常组织活性清除率。这些结果突显了在临床应用中将放射标记的αMSH类似物用于黑素瘤的分子成像和放射性核素治疗的潜力。