肿瘤靶向放射性诊疗药物创新研发策略  

Strategies for Innovative Development of Tumor-targeted Theranostic Radiopharmaceuticals

作　　者：黄旭虎 陈欢 李可欣 王宁 庄津 李洪玉 杜进 HUANG Xuhu;CHEN Huan;LI Kexin;WANG Ning;ZHUANG Jin;LI Hongyu;DU Jin(HTA Co.,Ltd.,Beijing 102413,China;CAEA Center of Excellence on Nuclear Technology Applications for Engineering and Industrialization of Radiopharmaceuticals,Beijing 102413,China;CNNC Engineering Research Center of Radiopharmaceuticals,Beijing 102413,China;China Isotope&Radiation Corporation,Beijing 100089,China)

机构地区：[1]原子高科股份有限公司,北京102413 [2]国家原子能机构核技术(放射性药物工程转化)研发中心,北京102413 [3]中核集团放射性药物工程技术研究中心,北京102413 [4]中国同辐股份有限公司,北京100089

出　　处：《原子能科学技术》2025年第4期769-782,共14页Atomic Energy Science and Technology

基　　金：中核集团基础研究项目;IAEA-CRP项目(28513)。

摘　　要：放射性药物作为核医学的重要组成部分,在疾病的诊断与治疗中展现出巨大的潜力。近年来,多款肿瘤靶向放射性诊疗药物获批上市,开启了诊疗一体化放射性药物的新时代,全球放射性药物产业呈现出蓬勃发展的态势,我国的肿瘤靶向放射性药物也呈现出逐步由仿制迈向创新的新发展格局。肿瘤诊疗放射性药物的创新研发是一项复杂的系统工程,需要从靶点、放射性核素、螯合剂、连接子和靶向配体等多个方面进行整体考虑和协同优化。本文从这五个方面展开综述,首先,总结了靶点和放射性核素的选择策略,并分析了针对新型放射性核素的螯合剂研发策略;随后,以靶向PSMA的放射性小分子药物为例,探讨了靶向配体和连接子的研发策略。此外,本文还总结了近年来在肿瘤放射性药物领域涌现出的新兴研发技术和策略,包括杂化、双靶点和共价等。最后,对肿瘤靶向放射性诊疗药物创新发展所面临的挑战进行了总结和分析,并对其未来发展方向进行了展望,期望能为我国放射性药物的创新发展提供参考。Radiopharmaceutical is an essential component of nuclear medicine and have demonstrated significant potential in disease diagnosis and treatment.In recent years,several tumor-targeted theranostic radiopharmaceuticals have been approved for market launch,ushering in a new era of targeted radionuclide therapy and theranostics.The global radiopharmaceutical industry is experiencing vigorous growth,and the research and development of tumor-targeted radiopharmaceuticals in China is transitioning from generic drugs to innovative drugs.The innovation of tumor-targeted radiopharmaceuticals is a complex systematic engineering task which requires comprehensive consideration and synergistic optimization of multiple aspects,including target,radionuclide,chelator,linker,and targeting ligand.In this paper,the above five aspects were reviewed to provide insights for the innovative development of radiopharmaceuticals.First,the strategies for selecting target and radionuclide were summarized and the development strategies of chelator for novel radionuclides were analyzed.Subsequently,taking PSMA-targeted radiopharmaceuticals based on small molecules as examples,the development strategies for targeting ligand and linker were discussed.Additionally,the emerging novel technologies and strategies for the development of theranostic radiopharmaceuticals,including radiohybrid strategies,dual-target strategies and covalent strategies were described.Finally,the challenges faced by the innovative development of tumor targeted radiopharmaceuticals were summarized and analyzed,and the future direction was prospected,with the hope of providing reference for the innovative development of radiopharmaceuticals in China.

关 键 词：肿瘤靶向 放射性诊疗药物 创新策略 

分 类 号：TL92.3[核科学技术—核燃料循环与材料] R817[医药卫生—影像医学与核医学]