用于恶性肿瘤治疗的^(225)Ac放射性药物的研究现状与展望  

Progress of ^(225)Ac-Labelled Radiopharmaceuticals for Cancer Treatment

作　　者：柳佳娣 徐度玲 李鸿岩[1,2,3,4,5] 张红 LIU Jia-di;XU Du-ling;LI Hong-yan;ZHANG Hong(Department of Medicine,Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,China;Gansu Provincial Isotope Laboratory,Lanzhou 730300,China;School of Nuclear Science and Technology,University of Chinese Academy of Sciences,Beijing 100039,China;Advanced Energy Science and Technology Guangdong Laboratory,Huizhou 516006,China;Key Laboratory of Heavy Ion Radiation Biology and Medicine,Chinese Academy of Sciences,Lanzhou 730000,China)

机构地区：[1]中国科学院近代物理研究所医学物理研究室,甘肃兰州730000 [2]甘肃省同位素实验室,甘肃兰州730300 [3]中国科学院大学核科学与技术学院,北京100039 [4]先进能源科学与技术广东省实验室,广东惠州516006 [5]中国科学院重离子辐射生物学与医学重点实验室,甘肃兰州730000

出　　处：《核化学与放射化学》2024年第1期46-53,I0005,共9页Journal of Nuclear and Radiochemistry

基　　金：甘肃省杰出青年基金项目(23JRRA1349);甘肃省重大科技项目(232DFA014);中央引导地方科技发展资金(甘肃)(YDZX20216200001201);中科院西部青年学者项目(E223221YXB);国家自然科学基金项目(11875061);甘肃省陇原青年创新创业人才项目(E139222SR0);广东省自然科学基金项目(2021A1515010027)。

摘　　要：^(225)Ac具有半衰期较长(10 d)、射程短(<100μm)和高能量沉积(80~100 keV/μm)等优点,是重要的医用α核素之一。^(225)Ac衰变产生的高传能线密度α粒子可以导致肿瘤细胞的DNA双链断裂,具有重要的临床应用价值。本文综述了^(225)Ac的衰变特性、生产来源以及^(225)Ac与靶向配体偶联的螯合剂,总结了^(225)Ac-前列腺特异性膜抗原(PSMA)-617、^(225)Ac-PMSA-I&T、^(225)Ac-1,4,7,10-四氮杂环十二烷-1,4,7,10-四羧酸(DOTA)-SP和^(225)Ac-1,4,7,10-四氮杂环十二烷-N,N′,N″,N-四乙酸d-苯丙氨酸1-酪氨酸3-奥曲肽(DOTATE)等药物在前列腺癌、脑胶质瘤、乳腺癌和肺癌治疗中的研究及临床应用进展,展望了^(225)Ac治疗药物研发面临的困难与挑战,以期为^(225)Ac放射性药物在恶性肿瘤治疗中的研究与应用提供参考。^(225)Ac with the advantages of longer half-life(10 d),shorter range(<100μm)and high energy deposition(80-100 keV/μm)compared with other medical isotopes,is one of the most important alpha-emitting nuclides.Theαparticles emitted by ^(225)Ac can cause DNA double-strand breaks in tumor cells,which is more favourable in clinical application.This review delineates the decay characteristics and production methodologies of ^(225)Ac,alongside detailing the conjugation of ^(225)Ac with target-specific ligands through various chelation strategies.It encapsulates the advancements in research and clinical applications of ^(225)Ac-labeled compounds,including ^(225)Ac-prostate-specific membrane antigen(PSMA)-617,^(225)Ac-PSMA-I&T,^(225)Ac-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)-SP,and ^(225)Ac-1,4,7,10-tetraazacyclododecane-N,N′,N″,N-tetraacetic acid d-phenylalanine1-tyrosine3-octreotide(DOTATE),in the therapeutic regimes for prostate cancer,gliomas,breast carcinoma,and pulmonary malignancies.The difficulties and challenges of ^(225)Ac-labelled radiopharmaceutical are also forecasted,in order to provide reference for the research and application of ^(225)Ac-labelled radiopharmaceuticals in the treatment of malignant tumors.

关 键 词：^(225)Ac α核素 治疗 癌症 

分 类 号：R817.8[医药卫生—影像医学与核医学]