Molecular Imaging and Radionuclide Therapy of Melanoma Targeting the Melanocortin 1 Receptor.

IF 2.2 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS
Chengcheng Zhang, Kuo-Shyan Lin, François Bénard
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引用次数: 13

Abstract

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.

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Abstract Image

Abstract Image

靶向黑色素皮质素1受体的黑色素瘤分子成像和放射性核素治疗。
黑色素瘤是一种晚期转移性致命疾病,早期诊断和准确分期是治疗黑色素瘤的关键。黑色素皮质素1受体(melanocortin 1 receptor, MC1 R)在原发性和转移性黑色素瘤中过表达,其内源性配体α-促黑素细胞激素(melanocytstimulating hormone, αMSH)已被广泛研究,用于开发针对MC1 R的分子成像和黑色素瘤治疗。天然α - msh由于体内稳定性较低,不适合用于此目的。非天然氨基酸取代极大地稳定了肽,而通过内酰胺桥环化和金属配位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αMSH类似物的发展和体外和体内特性,包括99mTc-, 111In-, 67ga -和125i标记αMSH类似物,用于单光子发射计算机断层成像;68Ga-, 64Cu-或18f标记的αMSH类似物用于正电子发射断层成像;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α - msh类似物在B16F1和B16F10小鼠黑色素瘤临床前模型中显示出高肿瘤摄取和快速正常组织活性清除的良好效果。这些结果突出了放射性标记α - msh类似物在黑色素瘤分子成像和放射性核素治疗中的临床应用潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Imaging
Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology
自引率
3.60%
发文量
21
期刊介绍: Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.
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