The production and separation of 161Tb with high specific activity at the University of Utah

Abstract

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_1/2 = 6.95 days), which undergoes beta emission and shares similar decay properties as ¹⁷⁷Lu (FDA-approved as LUTATHERA® and PLUVICTO®). Besides beta emission, ¹⁶¹Tb 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, ${}_{64}{}^{160}Gd\left(n,\gamma \right){}_{64}{}^{161}Gd\to \left(3.66\min ,{\beta }^{-}\right){}_{65}{}^{161}Tb$, from ¹⁶⁰Gd targets. However, a key challenge in utilizing ¹⁶¹Tb 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 ¹⁶¹Tb using low flux research reactors (mean thermal (<0.625 eV) neutron flux: $1.356\times {10}^{12}n\bullet {\text{cm}}^{-2}\bullet s^{-1}$) like the University of Utah TRIGA Reactor, using enriched ¹⁶⁰Gd₂O₃ targets (1.5 ± 0.3 μCi of ¹⁶¹Tb per mg of ¹⁶⁰Gd 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, ¹⁶¹Tb 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 HNO₃) methods. This resulted in high apparent molar activities of [¹⁶¹Tb]Tb-DOTA (113 ± 3 MBq/nmol), demonstrating high purity ¹⁶¹Tb relevant for potential future preclinical applications.