Canadian Nuclear Laboratories, 286 Plant Road, Chalk River, Ontario, K0J 1J0, Canada.
Canadian Nuclear Laboratories, 286 Plant Road, Chalk River, Ontario, K0J 1J0, Canada.
Appl Radiat Isot. 2020 Oct;164:109262. doi: 10.1016/j.apradiso.2020.109262. Epub 2020 Jun 15.
Targeted Alpha Therapy (TAT) has demonstrated considerable promise in the treatment of a range of cancers in both preclinical and, more recently clinical research. In particular, work with the alpha-emitting radionuclide Ac has been effectively employed due to the relatively rapid decay cascade that leads to 4 alpha and 2 beta emissions. One limitation for TAT has been caused by access to the vital radionuclide. Traditionally, Ac has been sourced from thorium/actinium generators based on the alpha decay of stockpiles of Th. Th is itself the alpha-decay product from U. Due to proliferation issues associated with U, only three thorium/actinium generators have been reported in the literature, capable of supporting clinical research. This paper describes the construction and operation of a thorium/actinium radionuclide generator at the Canadian Nuclear Laboratories, capable of supporting preclinical and limited clinical research in the area of TAT. Thorium was recovered and purified by a combination of anion exchange and extraction chromatography from aged U stockpiles. A separation scheme for Ra and Ac has been developed, based upon the chemical composition of the thorium material to allow for regular, routine milkings capable of supplying up to 3.7 GBq (100 mCi) of radiochemically pure Ac annually. This routine separation is accomplished using a combination of anion exchange chromatography to separate Ac and Ra isotopes from Th and extraction chromatography employing TEVA and DGA-N resins to separate actinium from radium and breakthrough thorium.
靶向阿尔法治疗(TAT)在临床前和最近的临床研究中已经在治疗多种癌症方面显示出了巨大的潜力。特别是,由于相对较快的衰变级联,导致 4 个阿尔法和 2 个贝塔发射,使用发射阿尔法粒子的放射性核素 Ac 进行的工作已经得到了有效的应用。TAT 的一个限制因素是获取重要的放射性核素。传统上,Ac 是从基于 Th 中储备的 Th/Ac 阿尔法衰变的 thorium/actinium 发生器中获得的。Th 本身就是 U 的阿尔法衰变产物。由于与 U 相关的增殖问题,文献中仅报道了三个能够支持临床研究的 thorium/actinium 发生器。本文介绍了加拿大核实验室 thorium/actinium 放射性核素发生器的构建和运行情况,该发生器能够支持 TAT 领域的临床前和有限的临床研究。Th 通过从老化的 U 储备中使用阴离子交换和萃取色谱法的组合进行回收和纯化。已经开发出了一种 Ra 和 Ac 的分离方案,该方案基于 thorium 材料的化学成分,允许定期进行常规的“挤奶”操作,每年能够供应高达 3.7GBq(100mCi)的放射化学纯 Ac。这种常规分离是通过阴离子交换色谱法来分离 Ac 和 Ra 同位素与 Th,以及使用 TEVA 和 DGA-N 树脂的萃取色谱法来分离 actinium 与 radium 和穿透性 thorium 来完成的。