Automated astatination of biomolecules--a stepping stone towards multicenter clinical trials.
Automated astatination of biomolecules--a stepping stone towards multicenter clinical trials.
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DOI：
10.1038/srep12025
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发表时间：
2015-07-14
影响因子：
4.6
通讯作者：
Lindegren S
中科院分区：
文献类型：
--
作者：
Aneheim E;Albertsson P;Bäck T;Jensen H;Palm S;Lindegren S
为了促进靶向α治疗的多中心临床研究，有必要开发一种自动化的现场程序，用于将罕见的、短寿命的α发射放射性核素与生物分子缀合。Astatine-211是少数几种具有适当化学和物理性质的α放射性核素之一，可用于癌症的靶向治疗。由于发射的α粒子的射程非常短，这种疗法特别适合治疗隐匿性、播散性癌症。Astatin本身不是肿瘤特异性的;因此，它需要适当的肿瘤特异性靶向载体，其可以将辐射引导到癌细胞。因此，需要一种合适的方法将核素偶联到载体上。为了增加用于靶向α治疗的<$211放射性药物的可用性，它们的生产应该自动化。在这里，我们提出了一种方法，该方法将<$-211的干馏和用于生产放射性药物的合成模块结合到工艺平台中。该平台将标准化含锶放射性药物的生产，因此，它将促进专注于这种有前途但具有化学挑战性的α发射放射性核素的大型临床研究。在这项工作中，我们描述了工艺平台，我们证明了生产的两个astaine-211，临床前使用，和astatin-211标记的抗体。
To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies.