177Lu放射性治疗药物研究新进展

分别具有β^-、 α、俄歇电子以及内转换电子衰变的放射性核素，在放射性药物研发以及临床评估中得到广泛应用，其中¹⁷⁷Lu放射性治疗药物的研究在近年来得到了迅猛的发展，文献报道数量持续增长，¹⁷⁷Lu放射性治疗药物引发了放药研究领域的强烈关注。本文对近两年¹⁷⁷Lu标记的抗体、多肽、纳米颗粒，以及小分子放射性治疗药物临床前及临床研究最新进展进行综述。其中处于临床前研究的药物通过药物设计增强了靶向性，改进了药代动力学及生物性质；处于临床研究阶段的药物具有良好的安全性，对肿瘤发挥明显抑制作用，对延长患者生存期及提高患者的生存质量起到积极作用；对已有临床用药方式进行补充，如核素联合治疗、放化免疫联合治疗、诊疗一体化以及分批次用药方式；对临床用药的人体计量学数据进行补充，如¹⁷⁷Lu-RM2在GRPR前列腺癌治疗中的人体剂量学。

The Recent Research Development of 177Lu Radiopharmaceuticals

Various radionuclides emitting β^-, α particles, auger electrons and conversion electrons have been applied in radiopharmaceuticals development and corresponding clinical evaluations. Among these applied radionuclides, lutetium-177 related radiopharmaceuticals have attracted tremendous interest from the scientific field. There were in total less than 20 publications throughout last century. However, there emerged nearly 1000 publications on ¹⁷⁷Lu during the past ten years, indicating more efforts have been focus on ¹⁷⁷Lu. This article will review the development of preclinical and clinical trials of ¹⁷⁷Lu radiolabeled antibodies, peptides, nanoparticles as well as small molecules as therapeutical ¹⁷⁷Lu radiopharmaceuticals dating to the recent two years. In the preclinical part, the targetting property, pharmacokinetics and biological property have been improved by drug design. In the clinical part, the reviewed radiopharmaceuticals displayed excellent safety, obvious inhibitory effect on tumor, obvious effects on prolonging the patient survival as well as improving the patients’ quality of life; qualified supplementary on the current clinical administration ways such as combined radionuclide therapy, chemo-immuno-radiotherapy, radiotheranostics and seperated administrations; supplementary on the human dosimetry data such as first-in-human dosimetry of gastrin-releasing peptide receptor antagonist ［¹⁷⁷Lu］Lu-RM2.