Research Progress of Radionuclide-Labeled PSMA Ligands in the Diagnosis and Treatment of Prostate Cancer

doi:10.7538/tws.2019.youxian.017

Abstract

Abstract:

Prostate cancer (PCa) is a malignant solid tumor with a high incidence in middle-aged and elderly men. At present, the diagnosis and treatment of PCa is limited and the sensitivity of the diagnostic method is not high, which is extremely unfavorable for the early diagnosis and late detection of PCa patients. Prostate-specific membrane antigen (PSMA) is a type Ⅱ glutamate carboxypeptidase that is overexpressed on the surface of almost all PCa cells, and the degree of overexpression of PSMA increases with the progression, metastasis and recurrence of PCa, Therefore, PSMA can be used as a specific target for the diagnosis and treatment of PCa. In recent years, with the development of nuclear medicine instruments and radioactive molecular probes, some PET/CT and SPECT/CT molecular probes targeting PSMA, such as ¹¹¹In-capromab, ¹⁸F-DCFPyL, ^99mTc-MIP-1405, ¹³¹I-MIP-1095, ⁶⁸Ga-PSMA-11 and ¹⁷⁷Lu-PSMA-617 have received extensive attention and application in the diagnosis, staging, biochemical recurrence detection and treatment of PCa. In this review, the latest research progress of PSMA ligands is summarized from the aspects of ligand affinity, selectivity, structure-activity relationship, in vivo metabolism and clinical application, which is expected to be beneficial to the research and development of new generation of PSMA inhibitors.

Key words: prostate cancer, PSMA, PSMA ligands, radionuclide imaging

摘要：

前列腺癌（PCa）是一种在中老年男性中发生率很高的恶性实体肿瘤。目前，PCa的诊治方法有限且诊断方法的灵敏度不高，不利于PCa患者的早期诊治和晚期转移检测。前列腺特异性膜抗原（PSMA）是一种几乎在所有PCa细胞表面过度表达的Ⅱ型谷氨酸羧肽酶，同时PSMA的过表达程度随着PCa的进展、转移和复发而增加。因此，PSMA可作为PCa诊治的特异性靶点。近年来，随着核医学仪器及放射性分子探针的研发，一些靶向PSMA的PET/CT及SPECT/CT分子探针如¹¹¹In-capromab、¹⁸F-DCFPyL、^99mTc-MIP-1405、¹³¹I-MIP-1095、⁶⁸Ga-PSMA-11和¹⁷⁷Lu-PSMA-617等在PCa的诊断、分期、生化复发探测及治疗上得到广泛的关注和应用。本文主要综述PSMA配体的亲和力、选择性、构效关系、体内代谢及临床应用等，并总结PSMA抑制剂的最新研究进展，以期对新一代PSMA抑制剂的研发有所裨益。

关键词: 前列腺癌, 前列腺特异性膜抗原, PSMA配体, 放射性核素显像

LIU Jingru;ZHU Hong. Research Progress of Radionuclide-Labeled PSMA Ligands in the Diagnosis and Treatment of Prostate Cancer[J]. Journal of Isotopes, 2020, 33(4): 241-249.

刘敬如;朱虹. 放射性核素标记的PSMA配体在前列腺癌诊治中的研究进展[J]. 同位素, 2020, 33(4): 241-249.

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