Frantellizzi Viviana, Cosma Laura, Brunotti Gabriele, Pani Arianna, Spanu Angela, Nuvoli Susanna, De Cristofaro Flaminia, Civitelli Liana, De Vincentis Giuseppe
Department of Molecular Medicine and Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
Cancer Biother Radiopharm. 2020 Aug;35(6):437-445. doi: 10.1089/cbr.2019.3105. Epub 2020 Jan 20.
Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (Ra), the first-in-class α-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike Ra, the parent radionuclide Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of Th TAT in the treatment of several solid as well as hematologic malignancies.
靶向α治疗（TAT）能够将高剂量的局部辐射选择性地传递至癌细胞以及肿瘤微环境，同时将对周围正常细胞的毒性降至最低。镭-223（Ra）是首个被批准用于治疗骨转移去势抵抗性前列腺癌的α发射体，已显示出延长患者生存期的能力。靶向钍-227（Th）偶联物代表了一类用于TAT的新型治疗性放射性药物。它们由与螯合剂络合的α发射体Th组成，该螯合剂与肿瘤靶向单克隆抗体偶联。在这篇综述中，作者将重点关注这种治疗剂。在最近的研究中，钍标记的放射免疫偶联物在血清和体内条件下均表现出相关稳定性，并对细胞生长具有显著的抗原依赖性抑制作用。与镭不同，母体放射性核素钍可以形成高度稳定的螯合物，因此适用于靶向放射免疫治疗。作者讨论了钍TAT在治疗几种实体恶性肿瘤和血液系统恶性肿瘤方面未来的潜在作用。
