A simple and automated method for 161Tb purification and ICP-MS analysis of 161Tb
Scott McNeil, Michiel Van de Voorde, Chengcheng Zhang, Maarten Ooms, François Bénard, Valery Radchenko, Hua Yang
Abstract
Abstract Background 161 Tb is a radiolanthanide with the potential to replace 177 Lu in targeted radionuclide therapy. 161 Tb is produced via the neutron irradiation of [ 160 Gd]Gd 2 O 3 targets, and must be purified from 160 Gd and the decay product 161 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 161 Tb purification that is more suitable for automation with commercially available systems like TRASIS. Results 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 161 Tb, 159 Tb, 160 Gd, and 161 Dy was developed with the application of mass-shift by ammonia gas. Last, 161 Tb produced from the small SPE column method was used to assess the biodistribution of [ 161 Tb]Tb-crown-αMSH, and the results were comparable to the HPIC produced 161 Tb. Conclusions 161 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 160 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 161 Tb being assessed before the decay of the product, providing a useful tool for quality control.