Production and quality control of no-carrier-added 161Tb from enriched 160Gd target material

The therapeutic radionuclide terbium-161 ( 161 Tb) is a promising alternative to lutetium-177 ( 177 Lu) for targeted radionuclide therapy, particularly for treating micrometastases. However, its clinical development is constrained by limited production capacity and the need for efficient separation from irradiated targets. This study developed a scalable, two-stage chromatographic process for producing no-carrier-added (n.c.a.) 161 Tb, aiming to provide high-activity, high-purity material suitable for radiopharmaceutical development. High-purity n.c.a. [ 161 Tb]TbCl₃ was obtained via sequential chromatography using a self-synthesized lanthanide (LN) resin and a commercial diglycolamide (DGA) resin. A single production batch yielded 42.38 ± 0.05% GBq with a radioactive concentration of 83.7 ± 0.12% GBq/mL. The product met stringent quality specifications: radionuclidic purity ≥ 99.9%, radiochemical purity ≥ 99%, and a specific activity of 6.04 × 10 17 ±0.08% Bq/mol. Concentrations of metallic impurities (gadolinium, dysprosium, iron, copper, zinc, lead) were all below the required limits. The utility of the 161 Tb was demonstrated by successful preparation of [ 161 Tb]Tb-DOTATATE, which maintained a radiochemical purity > 95.8% after 72 h in saline at ambient temperature. A reliable and efficient method for the large-scale production of high-purity n.c.a. 161 Tb has been established. The two-stage LN/DGA resin process effectively separates 161 Tb from the target material and decay daughter, yielding a product with quality attributes suitable for clinical research. This work provides a crucial and accessible nuclide source to advance the development of ¹⁶¹Tb-based radiopharmaceuticals.