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苯甲酰胺衍生物放射性示踪剂靶向黑色素用于黑色素瘤成像和治疗:临床前/临床开发及与其他治疗方法的联合应用。

Benzamide derivative radiotracers targeting melanin for melanoma imaging and therapy: Preclinical/clinical development and combination with other treatments.

机构信息

Université Clermont Auvergne, INSERM, Imagerie Moléculaire et Stratégies Théranostiques, UMR1240, 58 Rue Montalembert, 63005 Clermont-Ferrand, Cedex, France; Department of Dermatology and Oncodermatology, CHU Estaing, 1 place Lucie et Raymond Aubrac, 63000 Clermont-Ferrand, France; Centre Jean Perrin, Clermont-Ferrand F-63011, France.

Université Clermont Auvergne, INSERM, Imagerie Moléculaire et Stratégies Théranostiques, UMR1240, 58 Rue Montalembert, 63005 Clermont-Ferrand, Cedex, France.

出版信息

Pharmacol Ther. 2021 Aug;224:107829. doi: 10.1016/j.pharmthera.2021.107829. Epub 2021 Mar 1.

DOI:10.1016/j.pharmthera.2021.107829
PMID:33662452
Abstract

Cutaneous melanoma arises from proliferating melanocytes, cells specialized in the production of melanin. This property means melanin can be considered as a target for monitoring melanoma patients using nuclear imaging or targeted radionuclide therapy (TRT). Since the 1970s, many researchers have shown that specific molecules can interfere with melanin. This paper reviews some such molecules: benzamide structures improved to increase their pharmacokinetics for imaging or TRT. We first describe the characteristics and biosynthesis of melanin, and the main features of melanin tracers. The second part summarizes the preclinical and corresponding clinical studies on imaging. The last section presents TRT results from ongoing protocols and discusses combinations with other therapies as an opportunity for melanoma non-responders or patients resistant to treatments.

摘要

皮肤黑色素瘤源于增殖的黑色素细胞,这些细胞专门负责生成黑色素。这一特性意味着黑色素可以被视为核成像或靶向放射性核素治疗 (TRT) 监测黑色素瘤患者的一个靶点。自 20 世纪 70 年代以来,许多研究人员已经表明,特定的分子可以干扰黑色素。本文综述了一些这样的分子:苯甲酰胺结构得到改进,以提高其用于成像或 TRT 的药代动力学。我们首先描述了黑色素的特性和生物合成,以及黑色素示踪剂的主要特征。第二部分总结了成像的临床前和相应的临床研究。最后一部分介绍了正在进行的方案中的 TRT 结果,并讨论了与其他疗法联合应用的机会,以应对黑色素瘤无反应者或对治疗有抗性的患者。

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