Practical Aspects of ¹⁶¹Tb Production

Background/Objectives: Terbium-161 is an interesting and promising theranostic radionuclide, thanks to its decay characteristics (T_1/2 = 6.95 d, E(β)_max = 593 keV, E(β)_av = 154 keV, E(γ) = 74.6 keV (10.2%)). Having similar chemical properties, it is considered as an alternative to currently used ¹⁷⁷Lu. In addition, ¹⁶¹Tb emits a significant amount of conversion and Auger electrons, which contribute to the enhancement of localised therapeutic effect. The aim of this paper is to describe the preparation of ¹⁶¹Tb in quantity and quality relevant for preclinical and early clinical studies and to provide practical notes on the preparation. Methods: No-carrier-added ¹⁶¹Tb has been repeatedly prepared by neutron irradiation of highly enriched ¹⁶⁰Gd targets (up to 98 mg of ¹⁶⁰Gd₂O₃) at nuclear reactor LVR-15 (CV Řež, Czech Republic) in four different irradiation positions. The separation and purification process of ¹⁶¹Tb from the bulk of ¹⁶⁰Gd target was performed by cation exchange chromatography with Dowex 50 W × 8 (H⁺ cycle, 200-400 mesh). Terbium-161 was obtained in ¹⁶¹TbCl₃ form and formulated into 0.1 M HCl solution. The γ-ray spectrometry was used for radionuclide identification and radionuclidic purity and the ICP-MS method for chemical purity measurements and specific activity determination. The DOTA labelling assay was performed, as described by Gracheva et al., providing an assessment of the apparent molar activity of the preparation in terms of its competitive interaction with stable daughter nuclide ¹⁶¹Dy. Results: Irradiations (59.2 h to 421.52 h) of enriched ¹⁶⁰Gd targets with mass ranging from 43.4 to 144.0 mg for ¹⁶⁰Gd(NO₃)₃ and from 12.5 to 98.3 mg for ¹⁶⁰Gd₂O₃ yielded 1.3-23.7 GBq of ¹⁶¹Tb. The separation yields of purified ¹⁶¹Tb varied from 85 to 99%, with the activities of 9.9-22.1 GBq and the highest achieved specific activity of the final product was 4.1 GBq/μg (of Tb). The DOTA chelator was radiolabelled with ¹⁶¹Tb at time points from 2 to 14 days after the end of separation (EOS). Conclusions: Based on our results, we describe practical aspects of terbium production at the laboratory scale with a particular focus on practical aspects and issues arising during the process that may surprise even experienced radiochemists, as lanthanoid separation is not always straightforward, even though it is well-known and has been extensively studied. The preparation of ¹⁶¹Tb in a n.c.a. form proceeds, according to the reported data, with high reproducibility and achieves significant activity levels suitable for both preclinical and clinical investigations by irradiation of highly enriched ¹⁶⁰Gd targets in LVR-15 reactor with subsequent separation and purification of ¹⁶¹Tb on cation exchange resin Dowex 50 W × 8(H⁺). The produced [¹⁶¹Tb]TbCl₃ is employed in subsequent experimental research and development for the labelling of preparations intended for preclinical applications.