Johns Hopkins University, School of Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, 1550 Orleans Street, Baltimore, MD 21287-0014.
Health Phys. 2019 Feb;116(2):175-178. doi: 10.1097/HP.0000000000001000.
Radiopharmaceutical therapy involves the use of radionuclides that are either conjugated to tumor-targeting agents (e.g., nanoscale constructs, antibodies, peptides, and small molecules) or that concentrate in tumors through natural physiological mechanisms that occur predominantly in neoplastic cells. In the latter category, radioiodine therapy of thyroid cancer is the prototypical and most widely implemented radiopharmaceutical therapy. In the category of radionuclide-ligand conjugates, antibody and peptide conjugates have been studied extensively. The efficacy of radiopharmaceutical therapy relies on the ability to deliver cytotoxic radiation to tumor cells without causing prohibitive normal tissue toxicity. After some 30 y of preclinical and clinical research, a number of recent developments suggest that radiopharmaceutical therapy is poised to emerge as an important and widely recognized therapeutic modality. These developments include the substantial investment in antibodies by the pharmaceutical industry and the compelling rationale to build upon this already existing and widely tested platform. In addition, the growing recognition that the signaling pathways responsible for tumor cell survival and proliferation are less easily and durably inhibited than originally envisioned has also provided a rationale for identifying agents that are cytotoxic rather than inhibitory. A number of radiopharmaceutical agents are currently undergoing clinical trial investigation; these include beta-particle emitters, such as Lu, that are being used to label antisomatostatin receptor peptides for neuroendocrine cancers and also prostate-specific membrane antigen targeting small molecules for prostate cancer. Alpha-particle-emitting radionuclides have also been studied for radiopharmaceutical therapy; these include At for glioblastoma, Ac for leukemias and prostate cancer, Pb for breast cancer, and Ra for prostate cancer. The alpha emitters have tended to show particular promise, and there is substantial interest in further developing these agents for therapy of cancers that are particularly difficult to treat.
放射性药物治疗涉及使用放射性核素，这些核素要么与肿瘤靶向剂结合（例如，纳米结构、抗体、肽和小分子），要么通过主要发生在肿瘤细胞中的自然生理机制在肿瘤中积聚。在后一类中，放射性碘治疗甲状腺癌是典型的、应用最广泛的放射性药物治疗方法。在放射性核素-配体结合物类别中，抗体和肽结合物已得到广泛研究。放射性药物治疗的疗效取决于将细胞毒性辐射递送到肿瘤细胞而不会引起不可接受的正常组织毒性的能力。经过大约 30 年的临床前和临床研究，一些最近的发展表明放射性药物治疗即将成为一种重要且广泛认可的治疗方式。这些发展包括制药行业对抗体的大量投资，以及建立在这个已经存在和广泛测试的平台上的强烈理由。此外，越来越认识到负责肿瘤细胞存活和增殖的信号通路比最初想象的更难和更持久地抑制，这也为确定具有细胞毒性而不是抑制性的药物提供了理由。目前有许多放射性药物正在进行临床试验研究；这些包括β粒子发射体，如用于标记神经内分泌癌的抗生长抑素受体肽的 Lu，以及用于前列腺癌的前列腺特异性膜抗原靶向小分子的 Lu。α粒子发射体也被研究用于放射性药物治疗；这些包括用于胶质母细胞瘤的 At，用于白血病和前列腺癌的 Ac，用于乳腺癌的 Pb，以及用于前列腺癌的 Ra。α发射器一直显示出特别有希望的前景，并且人们对进一步开发这些用于治疗特别难以治疗的癌症的药物有很大的兴趣。
