Nuclear Engineering Program, Department of Civil and Environmental Engineering, University of Utah, 110 Central Campus Dr. Rm 2000, Salt Lake City, UT, 84112, United States.
The Graduate Center of the City University of New York, New York, NY, 10016, United States; Department of Chemistry, Hunter College of the City University of New York, New York, NY, 10065, United States.
Appl Radiat Isot. 2024 Dec;214:111530. doi: 10.1016/j.apradiso.2024.111530. Epub 2024 Sep 25.
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.
放射性靶向治疗（TRT）是核医学中一个日益重要的研究领域，特别是在治疗癌性肿瘤方面。一种备受关注的用于 TRT 的放射性核素是铽-161（t = 6.95 天），它通过β发射，具有与镥（FDA 批准的 LUTATHERA®和 PLUVICTO®）相似的衰变特性。除了β发射外，Tb 还会发射大量的内转换和俄歇电子，进一步增强了其治疗潜力。铽-161 可以通过核反应堆通过间接中子俘获反应 G64160dn，γG64161d→3.66min，βT65161b，从 Gd 靶材中产生。然而，在将 Tb 用于 TRT 方面的一个关键挑战在于有效分离靶材和产物材料，以获得高比活度进行放射性标记。在这里，我们详细介绍了使用像犹他大学 TRIGA 反应堆这样的低通量研究反应堆（平均热（<0.625 eV）中子通量：1.356×10n·cm·s）生产无载体添加 Tb 的方法，使用富 GdO 靶材（每毫克 Gd 靶材每小时辐照产生 1.5 ± 0.3 μCi 的 Tb）。我们还开发了一种基于阳离子交换和萃取色谱的分离技术，适用于 mCi 级辐照，靶材超过 200 mg。在模拟的全规模辐照中，我们成功地使用阳离子交换（AG 50W-X8，使用 2-羟基异丁酸，pH 值为 4.75）和萃取色谱（LN 树脂，0.5-0.75 M HNO）方法从大量靶材中分离出 Tb。这导致了 [Tb]Tb-DOTA 的高表观摩尔活度（113 ± 3 MBq/nmol），表明 Tb 的纯度很高，适用于未来的临床前应用。
