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.