225Ac-PSMA治疗转移型去势抵抗性前列腺癌研究进展

The research progress of 225 Ac-PSMA in the treatment of metastatic castration resistant prostate cancer

前列腺癌在全球男性中的发病率高居第二位,也是我国男性患癌死亡的主要病因。转移型去势抵抗性前列腺癌(metastatic castration resistant prostate cancer,mCRPC)是前列腺癌进展的终末阶段,也是治疗的难点。既往治疗方式包括新型内分泌治疗、化疗、PARP抑制剂、免疫靶向治疗和放射性核素治疗等。前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)是放射性核素治疗的热门靶点,β核素177Lu已被美国食品药品监督管理局批准用于治疗PSMA阳性的mCRPC患者,α核素223Ra也逐渐进入我国研究者的视野被推荐用于治疗骨转移患者。225Ac在当前研究中显示出抗肿瘤活性显著、安全性相对较高的特点,存在广阔的应用前景。本文将从现状、疗效分析、毒性等方面对在国内鲜有报道的基于PSMA靶点的新放射性核素—锕元素(Actinium-225,225Ac)的相关治疗研究进展进行综述,以帮助临床工作者和科研人员把握前列腺癌放射性核素治疗的前沿动态,辅助其科学决策。遗憾的是,现有研究基本为单中心的回顾性研究,尚缺乏国际范围内的多中心、前瞻性队列研究和临床试验。225Ac治疗的主要副作用有口干症、肾毒性和血液学毒性(如贫血、白细胞减少和血小板减少)等。研究者们对于225Ac的毒性及其不良反应机制的了解仍不全面,对相关联合序贯疗法的研究还不够深入,因此距离正式获批应用于临床还有很多工作需要完成。

Prostate cancer(PCa)is the second highest incidence among men in the world,and it has gradually become the main cause of cancer death among males in China.Metastatic castration resistant prostate cancer(mCRPC)is the terminal stage of prostate cancer progression,which is arduous to treat.Previous treatments include novel hormone therapy(NHT),chemotherapy,PARP inhibitor therapy,immune and targeted therapy,radionuclide therapy and so on.Prostate specific membrane antigen(PSMA)is a popular target for radionuclide therapy.The β-nuclide 177 Lu has been approved by the U.S.Food and Drug Administration(FDA)for the treatment of PSMA-positive mCRPC patients.αradionuclide 223 Ra has gradually entered the field of vision of Chinese researches and is recommended for the treatment of patients with bone metastases.225 Ac shows significant anti-tumor activity in the treatment of mCRPC,and has the characteristics of good effect and relatively high safety,which has extensive prospects.This article will review the research progress of actinium(Actinium-225,225 Ac),a new radionuclide targeted on PSMA,which is rarely reported in China,from the aspects of current status,efficacy analysis and toxic effects,etc.,in order to help clinical workers to grasp the frontier trends of radionuclide treatment of prostate cancer and assist their scientific decision-making.Unfortunately,the existing studies are basically single-center retrospective studies,and there is still a lack of international multi-center,prospective cohort studies and clinical trials.The main side effects of 225 Ac treatment are xerostomia,nephrotoxicity and hematological toxicity(such as anemia,leukopenia and thrombocytopenia).The researchers'understanding of the toxicity of 225 Ac and its side reaction mechanism is still not comprehensive,and the research of related combined sequential therapy is not deep enough.So there is still numerous follow-up research work to be completed before it is officially approved for clinical patients.