摘要
225 Ac具有半衰期较长(10 d)、射程短(＜100 μm)和高能量沉积(80～100 keV/μm)等优点,是重要的医用a核素之一.225Ac衰变产生的高传能线密度a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225Ac的衰变特性、生产来源以及225Ac与靶向配体偶联的螯合剂,总结了225Ac-前列腺特异性膜抗原(PSMA)-617、225Ac-PMSA-I&T、225Ac-1,4,7,10-四氮杂环十二烷-1,4,7,10-四羧酸(DOTA)-SP和225Ac-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225Ac放射性药物在恶性肿瘤治疗中的研究与应用提供参考.
Abstract
225Ac with the advantages of longer half-life(10 d),shorter range(＜100 μm)and high energy deposition(80-100 keV/pm)compared with other medical isotopes,is one of the most important alpha-emitting nuclides.The a particles 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 225Ac,alongside detailing the conjugation of 225Ac with target-specific ligands through various chelation strat-egies.It encapsulates the advancements in research and clinical applications of 225 Ac-labeled compounds,including 225Ac-prostate-specific membrane antigen(PSMA)-617,225Ac-PSMA-I&T,225Ac-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)-SP,and 225Ac-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 225Ac-labelled radiopharmaceutical are also forecasted,in order to provide reference for the research and application of 225Ac-labelled radiopharmaceuticals in the treatment of malignant tumors.
基金项目
甘肃省杰出青年基金(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)
中国科学院西部青年学者项目(E223221YXB)
国家自然科学基金(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(2021A1515010027)
万方数据