A simple and automated method for 161Tb purification and ICP-MS analysis of 161Tb

Abstract

Background 161Tb is a radiolanthanide with the potential to replace 177Lu in targeted radionuclide therapy. 161Tb is produced via the neutron irradiation of [160Gd]Gd2O3 targets, and must be purified from 160Gd and the decay product 161Dy 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 161Tb 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 161Tb, 159Tb, 160Gd, and 161Dy was developed with the application of mass-shift by ammonia gas. Last, 161Tb produced from the small SPE column method was used to assess the biodistribution of [161Tb]Tb-crown-αMSH, and the results were comparable to the HPIC produced 161Tb. Conclusions 161Tb 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 160Gd 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 161Tb being assessed before the decay of the product, providing a useful tool for quality control.

Preclinical Evaluation of [155/161Tb]Tb-Crown-TATE—A Novel SPECT Imaging Theranostic Agent Targeting Neuroendocrine Tumours

“…161 Tb was produced via the neutron bombardment of enriched [ 160 Gd][Gd 2 O 3 (98.2%) targets using the high thermal neutron flux (3 × 10 14 neutrons/cm 2 /s) BR2 reactor at SCK-CEN (Belgium) [ 26 ] and subsequently purified at TRIUMF using a semi-automated TRASIS system with solid phase extraction (SPE) resins (TK211, TK 212, TK221) [ 27 ].…”

“…161 Tb was produced via the neutron bombardment of enriched [ 160 Gd][Gd 2 O 3 (98.2%) targets using the high thermal neutron flux (3 × 10 14 neutrons/cm 2 /s) BR2 reactor at SCK-CEN (Belgium) [ 26 ]. After cooling, the 161 Tb activity was purified using a semi-automated TRASIS system equipped with TrisKem solid phase extraction (SPE) resins (TK211, TK212, TK221 (Triskem, Bruz, France) at TRIUMF (Canada) as described by McNeil et al [ 27 ]. A radionuclidic purity of > 99% was determined using ICPMS for 161 Tb purified using this approach.…”

Terbium radionuclides for theranostic applications in nuclear medicine: from atom to bedside

“…Alternatively, Aziz and Artha reported the quantitative separation of terbium-161 from gadolinium targets using extraction chromatography on an LN resin column and sequential elution of gadolinium in 0.8 M HNO 3 solution and terbium in 3 M HNO 3 52 . More recently an automated lab-scale method was developed that relies on small solid-phase extraction using a combination of LN-type extraction resins, making it more compatible with automation using commercially available systems like the Trasis All-in-One system 53 . Using this technique, terbium-161 could be successfully purified from smaller scale targets with high radionuclide and chemical purity.…”

“…Using this technique, terbium-161 could be successfully purified from smaller scale targets with high radionuclide and chemical purity. Though the researchers have suggested that there is room for further improvements to minimize the presence of the gadolinium-160 target material and the dysprosium-161 decay product in the final terbium-161 sample, it remains evident that full automation of the purification process holds immense potential when it comes to upscaling production and managing larger quantities of target material 53 . These small modular systems could be interesting for final refinement of terbium-161 after bulk separation on a different location or system, or could be used for fast reprocessing of terbium-161 after several days of decay to remove the dysprosium-161 daughter reducing its interference during radiolabeling.…”

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

“…It is increasingly accepted that 161 Tb has therapeutic advantages compared to 177 Lu (vide supra), as well as similar production potential. A recent article by McNeil recognizes a confounding limitation of 161 Tb production, which has been spearheaded by groups at the Paul Scherrer Institute in Switzerland for the past several years, namely, that the highest quality productions of 161 Tb reported so far are constrained by the availability of uniquely small meshed ion exchange resin materials (McNeil et al 2022). While other high performance ion chromatography-(HPIC-) based separation methods are being developed elsewhere, high-pressure processes present particular challenges to scale-up and are substantially more challenging to implement than the cartridge-based method reported here using materials that are readily commercially available at reasonable cost.…”