功能化PSMA在前列腺癌核素靶向治疗中的研究进展  

Recent Progress of Functionalized PSMA in Radionuclide Targeted Therapy for Prostate Cancer

作　　者：任亚楠 刘特立 李大鹏 李慧[1] 丁缙 朱华[1,2] 杨志 REN Ya’nan;LIU Teli;LI Dapeng;LI Hui;DING Jin;ZHU Hua;YANG Zhi(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Department of Nuclear Medicine,Peking University Cancer Hospital&Institute,Beijing 100142,China;School of Medicine,Guizhou University,Guiyang 550025,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [2]贵州大学医学院,贵阳550025

出　　处：《肿瘤防治研究》2020年第12期975-979,共5页Cancer Research on Prevention and Treatment

基　　金：北京市自然科学基金(7194246)。

摘　　要：前列腺癌(PCa)是男性生殖系统发病率最高的恶性肿瘤。研究证实,前列腺特异性膜抗原(PSMA)是一种有效的前列腺癌诊疗靶点。治疗核素177Lu/90Y标记的抗PSMA小分子/多肽/单抗表现出重要的抑癌活性,但也产生腺体、骨髓的特异性摄取和肾脏的非特异性摄取带来的正常器官损伤。而且小分子/多肽易于经循环系统清除,基于小分子/多肽的放射性靶向治疗往往需要较高剂量或频繁给药,导致在抑制肿瘤的同时,也产生难以预料的器官毒性。放射性核素靶向治疗依赖于将放射性核素传递到肿瘤表达的受体,但配体与受体结合容量有限。为提高核素的使用效率,延长核素治疗型PSMA分子探针的体内代谢,增加靶/非靶比值,对PSMA分子探针进行功能化修饰以期改善药代动力学行为的研究已经取得了巨大进展。本文就近年功能化PSMA分子探针在前列腺癌核素靶向治疗中的临床转化及临床研究展开综述。Prostate cancer(PCa)is the most common malignant tumor in the male reproductive system.Prostate specific membrane antigen(PSMA)is an effective target for the diagnosis and treatment of prostate cancer.The anti-PSMA small molecule/polypeptide/monoclonal antibody labeled with the therapeutic nuclides 177Lu/90Y has shown important anti-tumor activity,but it also produces specific uptake of glands,bone marrow and kidneys,which leads to normal organs’damage.In addition,small molecules/peptides are easy to be cleared by the circulatory system.Radionuclide targeted therapy based on small molecules/peptides often requires high doses or frequent administration,which leads to unpredictable organ toxicity while inhibiting tumors.Radionuclide targeted therapy relies on the delivery of radionuclides to tumor-expressed receptors,but the binding capacity of ligands to receptors is limited.In order to improve the use efficiency of radionuclides,prolong the metabolism of radionuclide therapeutic PSMA molecular probes as well as increase the ratio of target to non target,great progress has been made in the study of functional modification of PSMA molecular probes which can improve the pharmacokinetic behavior.In this paper,we summarize the recent clinical translation and clinical research of functional nuclide targeting PSMA molecular probe in the treatment of prostate cancer.

关 键 词：前列腺癌 前列腺特异性膜抗原 放射性配体治疗 功能化修饰 体内代谢 临床转化 

分 类 号：R737.25[医药卫生—肿瘤]