Targeted Alpha Therapy with Thorium-227
Targeted Alpha Therapy with Thorium-227
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DOI：
10.1089/cbr.2019.3105
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发表时间：
2020-08-01
影响因子：
3.4
通讯作者：
De Vincentis, Giuseppe
中科院分区：
文献类型：
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作者：
Frantellizzi, Viviana;Cosma, Laura;De Vincentis, Giuseppe
靶向α治疗（TAT）可以选择性地向癌细胞和肿瘤微环境提供高局部辐射负荷，同时将对正常周围细胞的毒性降到最低。镭-223 (Ra-223)，被批准用于骨转移性去势抵抗性前列腺癌的一流α -发射器，已显示出延长患者生存期的能力。靶向钍-227 （Th-227）缀合物是一类新的治疗TAT的放射性药物。它们由α -发射器（227）Th络合到结合肿瘤靶向单克隆抗体的螯合剂组成。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（227），th标记的放射免疫偶联物在血清和体内条件下都显示出相关的稳定性，并具有显著的抗原依赖性抑制细胞生长。与（223）Ra不同，母体放射性核素（227）Th可以形成高度稳定的螯合剂复合物，因此可用于靶向放射免疫治疗。作者讨论了（227）thtat在治疗几种实体和血液系统恶性肿瘤中的潜在作用。
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-223), the first-in-class alpha-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (Th-227) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the alpha-emitter(227)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(227)Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike(223)Ra, the parent radionuclide(227)Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of(227)Th TAT in the treatment of several solid as well as hematologic malignancies.