锕-225的生产及在肿瘤靶向治疗中的应用  

Production of actinium-225 and its clinical application in tumor targeted therapy

作　　者：丁立新 杨志[1] DING Lixin;YANG Zhi(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Nuclear Medicine,Peking University Cancer Hospital&Institute,Beijing 100142,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

出　　处：《中华肿瘤防治杂志》2024年第21期1326-1332,共7页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(82171980)。

摘　　要：目的对α核素锕-^(225)(^(225)Ac)的生产技术、物理/化学特性以及^(225)Ac标记化合物的重要临床研究结果进行综述,以期为今后^(225)Ac的生产及药物研制提供参考。方法以“Ac-^(225)、targeted alpha therapy(TAT)、tumor/cancer treatment、isotope production、radiolabelling”为英文关键词;以“^(225)Ac、靶向α粒子疗法、肿瘤/癌症治疗、同位素生产、放射性标记”为中文关键词,检索PubMed和中国知网数据库1999-01-01-2024-04-12相关文献。纳入标准:(1)^(225)Ac的核特性介绍;(2)^(225)Ac核素的生产方法;(3)^(225)Ac的螯合剂及化学标记方法;(4)^(225)Ac标记化合物及其在肿瘤靶向治疗方面的应用。排除标准:会议摘要及中文学位论文等非正式发表的文献。依据纳入和排除标准,最终纳入53篇文献进行分析。结果^(225)Ac具有相对较长半衰期(T_(1/2)=9.92 d)、高传能线密度(150 keV/μm)和短射程(47~85μm)等物理特性,是肿瘤靶向α治疗(TAT)理想候选核素。目前通过化学分离从钍-^(229)(^(229)Th)的现有库存中生产^(225)Ac不能满足预计的需求。因此,各种替代生产^(225)Ac的路线正在研究,可能需要组合不同生产路线来满足日益增长的需求。^(225)Ac标记化合物对于前列腺癌、脑胶质瘤及神经内分泌肿瘤等恶性肿瘤具有良好的临床应用前景。但仍然存在一些技术上的挑战,例如患者最优剂量及器官毒性等。结论^(225)Ac标记化合物虽然对多种临床难治性肿瘤发挥着独特优势,但仍然面临^(225)Ac供应能力不足、提高体内稳定性及给药剂量合理性等相关问题的挑战。Objective To review the production techniques,physical/chemical properties of theα-emitting radionuclide actinium-225(^(225)Ac),and important clinical trial results of^(225)Ac-labeled compounds,which can provide a reference for the future production and drug development of^(225)Ac.Methods A comprehensive literature search was conducted in the PubMed and CNKI databases by using Chinese and English keywords such as"Ac-225,Targeted alpha therapy(TAT),Tumor/Cancer treatment,Isotope production,Radiolabelling"from January 1,1999 to April 12,2024.Inclusion criteria:(1)the introduction of^(225)Ac's nuclear characteristics;(2)the production method of^(225)Ac nuclide;(3)the chelating agent and chemical labeling method of^(225)Ac;(4)the^(225)Ac-labeled compounds and its application in tumor targeted therapy.Exclusion criteria was informal publications such as conference abstracts and Chinese degree theses.A total of 53 articles were ultimately included.Results Actinium-225 is the perfect candidate for tumor TAT and has physical characteristics such as relatively long half-life(T_(1/2)=9.92 d),high linear energy transfer(150 keV perμm),and short ranges(47-85μm).The production via chemical separation from existing stocks of thorium-229(^(229)Th)cannot meet the anticipated demand.Consequently,a variety of alternative production routes for^(225)Ac are being investigated,and a combination of different sources will likely be required to meet the growing need.^(225)Ac-labeled compounds have a good clinical application prospect for prostate cancer,brain glioma,neuroendocrine tumors and other malignant tumors.However,there are still some technical challenges,such as optimal dosage and organ toxicity.Conclusion Despite unique advantage in a variety of clinically refractory tumors has been presented,^(225)Ac-labeled compounds are still challenged by issues related to the insufficient supply capacity of^(225)Ac,in vivo stability,and administration dosage.

关 键 词：靶向α治疗 锕-225 核素生产 放射性标记 临床应用 综述文献 

分 类 号：R817.5[医药卫生—影像医学与核医学]