The production and separation of Tb with high specific activity at the University of Utah.

Targeted radiotherapy (TRT) is an increasingly prominent area of research in nuclear medicine, particularly in the context of treating cancerous tumors. One radionuclide of considerable interest for TRT is terbium-161 (t = 6.95 days), which undergoes beta emission and shares similar decay properties as Lu (FDA-approved as LUTATHERA® and PLUVICTO®). Besides beta emission, Tb also emits a significant number of conversion and Auger electrons further enhancing its therapeutic potential. Terbium-161 can be produced using nuclear reactors through an indirect neutron capture reaction, G64160dn,γG64161d→3.66min,βT65161b, from Gd targets. However, a key challenge in utilizing Tb for TRT lies in effectively separating target and product materials to attain high specific activity for radiolabeling. Here, we detail the production of no-carrier added Tb using low flux research reactors (mean thermal (<0.625 eV) neutron flux: 1.356×10n∙cm∙s) like the University of Utah TRIGA Reactor, using enriched GdO targets (1.5 ± 0.3 μCi of Tb per mg of Gd target per hour of irradiation). We also developed a separation technique based on cation exchange and extraction chromatography, suitable for mCi level irradiations with targets exceeding 200 mg. In a simulated full-scale irradiation, Tb was successfully isolated from large mass targets using cation exchange (AG 50W-X8, with 2-hydroxyisobutyric acid at 70 mM, pH 4.75) and extraction chromatography (LN Resin, 0.5-0.75 M HNO) methods. This resulted in high apparent molar activities of [Tb]Tb-DOTA (113 ± 3 MBq/nmol), demonstrating high purity Tb relevant for potential future preclinical applications.