Production and purification of research scale 161Tb using cation-exchange semi-preparative HPLC for radiopharmaceutical applications

Patrick Bokolo; Madhushan Serasinghe; Marina Kuchuk; Jim Guthrie; Mary Embree; Stacy Wilder; Dmitri G. Medvedev; Cathy S. Cutler; D. Scott Wilbur; Yawen Li; Carolyn J. Anderson; Silvia S. Jurisson; Heather M. Hennkens

doi:10.1515/ract-2024-0363

Article

Production and purification of research scale ¹⁶¹Tb using cation-exchange semi-preparative HPLC for radiopharmaceutical applications

Patrick Bokolo , Madhushan Serasinghe , Marina Kuchuk , Jim Guthrie , Mary Embree , Stacy Wilder , Dmitri G. Medvedev , Cathy S. Cutler , D. Scott Wilbur , Yawen Li , Carolyn J. Anderson , Silvia S. Jurisson and Heather M. Hennkens

Published/Copyright: April 22, 2025

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From the journal Radiochimica Acta Volume 113 Issue 6

Abstract

Terbium-161 (¹⁶¹Tb) is emerging as a promising radionuclide for cancer therapy due to its favorable nuclear properties that are similar to clinically established lutetium-177 (¹⁷⁷Lu) along with its therapeutic edge arising from the higher number of Auger and conversion electrons per decay. These low energy electrons result in higher cytotoxicity within a short range of the decaying nuclei to enhance therapeutic efficacy. Despite these promising characteristics, a significant challenge remains in the lack of a domestic ¹⁶¹Tb supply in the United States, which poses an obstacle to the advancement of ¹⁶¹Tb-based radiopharmaceutical research and development. This study developed a reliable cation-exchange high-performance liquid chromatography-based method for purification of reactor-produced ¹⁶¹Tb at quantities suitable to support research and preclinical studies. The purified ¹⁶¹Tb product showed high radionuclidic purity with excellent radiochemical purity, and the successful labeling studies with the DOTA chelator and DOTA-TATE peptide demonstrated the effective incorporation of the purified ¹⁶¹Tb into radiopharmaceuticals designed for targeted cancer therapy.

Keywords: alpha-hydroxyisobutyric acid; cation-exchange resin; high-performance liquid chromatography; lanthanide separation; nuclear medicine; terbium-161

Corresponding author: Heather M. Hennkens, Department of Chemistry, University of Missouri, 601 South College Avenue, Columbia, 65211, MO, USA; and Research Reactor Center (MURR), University of Missouri, Columbia, 65211, MO, USA, E-mail: HennkensH@missouri.edu

Research ethics: Not applicable.
Informed consent: Not applicable.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: This material is based upon work supported by the U.S. Department of Energy, Office of Science, Office of Isotope R&D and Production program under Award Number DE-SC0022235. Additional support was provided by the University of Missouri-Columbia (MU Research Reactor and Department of Chemistry). We acknowledge the National Science Foundation for the award BCS-0922374 to the University of Missouri, which funded the ICP-MS equipment used in this research.
Data availability: Not applicable.
Disclaimer: This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/ract-2024-0363).

Received: 2024-11-09

Accepted: 2025-04-05

Published Online: 2025-04-22

Published in Print: 2025-06-26

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Supplementary Material

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Keywords for this article

alpha-hydroxyisobutyric acid; cation-exchange resin; high-performance liquid chromatography; lanthanide separation; nuclear medicine; terbium-161