McNeil Scott W, Van de Voorde Michiel, Zhang Chengcheng, Ooms Maarten, Bénard François, Radchenko Valery, Yang Hua
Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3, Canada.
NURA Research Group, Belgian Nuclear Research Center (SCK CEN), Boeretang 200, 2400, Mol, Belgium.
EJNMMI Radiopharm Chem. 2022 Dec 2;7(1):31. doi: 10.1186/s41181-022-00183-y.
Tb is a radiolanthanide with the potential to replace Lu in targeted radionuclide therapy. Tb is produced via the neutron irradiation of [Gd]GdO targets, and must be purified from Gd and the decay product Dy prior to use. Established purification methods require complex conditions or high-pressure ion chromatography (HPIC) which are inconvenient to introduce in a broad user community. This study aims to find a simpler small solid-phase extraction (SPE) column method for Tb purification that is more suitable for automation with commercially available systems like TRASIS.
We first tested the distribution coefficients on TK211 and TK212 resins for the separation of Gd, Tb, and Dy, and subsequently developed a method to separate these metal ions, with an additional TK221 resin to concentrate the final product. A side-by-side comparison of the products purified using this new method with the HPIC method was undertaken, assessing the radionuclidic purity, chemical purity regarding Gd and Dy, and labeling efficiency with a standard chelate (DOTA) and a novel chelate (crown). The two methods have comparable radionuclidic purity and labeling efficiency. The small SPE column method reduced Gd content to nanogram level, although still higher than the HPIC method. An ICP-MS method to quantify Tb, Tb, Gd, and Dy was developed with the application of mass-shift by ammonia gas. Last, Tb produced from the small SPE column method was used to assess the biodistribution of [Tb]Tb-crown-αMSH, and the results were comparable to the HPIC produced Tb.
Tb was successfully purified by a semi-automated TRASIS system using a combination of TrisKem extraction resins. The resulting product performed well in radiolabelling and in vivo experiments. However, improvement can be made in the form of further reduction of Gd target material in the final product. An ICP-MS method to analyze the radioactive product was developed. Combined with gamma spectroscopy, this method allows the purity of Tb being assessed before the decay of the product, providing a useful tool for quality control.
铽是一种放射性镧系元素，有潜力在靶向放射性核素治疗中替代镥。铽通过对[钆]钆氧靶进行中子辐照产生，在使用前必须从钆及其衰变产物镝中纯化出来。既定的纯化方法需要复杂的条件或高压离子色谱法（HPIC），而在广大用户群体中引入这些方法并不方便。本研究旨在找到一种更简单的用于铽纯化的小型固相萃取（SPE）柱方法，该方法更适合与TRASIS等市售系统实现自动化。
我们首先测试了TK211和TK212树脂对钆、铽和镝分离的分配系数，随后开发了一种分离这些金属离子的方法，并用额外的TK221树脂浓缩最终产物。对使用这种新方法纯化的产物与HPIC方法纯化的产物进行了并行比较，评估了放射性核素纯度、关于钆和镝的化学纯度以及与标准螯合剂（DOTA）和新型螯合剂（冠醚）的标记效率。这两种方法具有可比的放射性核素纯度和标记效率。小型SPE柱方法将钆含量降低到纳克水平，尽管仍高于HPIC方法。通过应用氨气质量转移开发了一种用于定量铽、钆、铽和镝的电感耦合等离子体质谱法（ICP-MS）。最后，用小型SPE柱方法产生的铽用于评估[铽]铽-冠醚-α促黑素的生物分布，结果与HPIC产生的铽相当。
铽通过使用TrisKem萃取树脂组合的半自动TRASIS系统成功纯化。所得产物在放射性标记和体内实验中表现良好。然而，最终产物中钆靶材料的进一步减少形式仍可改进。开发了一种用于分析放射性产物的ICP-MS方法。结合伽马能谱法，该方法允许在产物衰变前评估铽的纯度，为质量控制提供了有用的工具。
