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

Journal Article · · Applied Radiation and Isotopes
 [1];  [2];  [3];  [4];  [5];  [2];  [2];  [2]
  1. University of Utah, Salt Lake City, UT (United States); University of Utah
  2. University of Utah, Salt Lake City, UT (United States)
  3. The Graduate Center of the City University of New York, NY (United States); Hunter College of the City University of New York, NY (United States)
  4. University of Missouri, Columbia, MO (United States); University of Missouri Research Reactor Center (MURR), Columbia, MO (United States)
  5. University of Missouri Research Reactor Center (MURR), Columbia, MO (United States)

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 (t1/2 = 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, $$^{160}_{64}$$Gd(n,γ) $$^{161}_{64}$$Gd → (3.7 min, β) $$^{161}_{65}$$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 ×1012 n • cm–2 • 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 milligrams. 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. Here, 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.

Research Organization:
University of Utah, Salt Lake City, UT (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Office of Isotope R&D and Production (IRP)
Grant/Contract Number:
SC0020955
OSTI ID:
2475657
Journal Information:
Applied Radiation and Isotopes, Journal Name: Applied Radiation and Isotopes Vol. 214; ISSN 0969-8043
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Opportunities and potential challenges of using terbium-161 for targeted radionuclide therapy in clinics journal July 2023
First-in-human administration of terbium-161-labelled somatostatin receptor subtype 2 antagonist ([161Tb]Tb-DOTA-LM3) in a patient with a metastatic neuroendocrine tumour of the ileum journal March 2024
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Extension of the energy range of the experimental activation cross-sections data of longer-lived products of proton induced nuclear reactions on dysprosium up to 65MeV journal April 2015
Photonuclear production of medical radioisotopes 161Tb and 155Tb journal August 2023
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Production and characterization of no-carrier-added 161Tb as an alternative to the clinically-applied 177Lu for radionuclide therapy journal July 2019
Radiochemical Separation of 161Tb from Gd/Tb Matrix Using Ln Resin Column journal November 2016
Matched Pair Theranostics journal November 2019
161Tb-DOTATOC Production Using a Fully Automated Disposable Cassette System: A First Step Toward the Introduction of161Tb into the Clinic journal May 2023
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Terbium radionuclides for theranostic applications in nuclear medicine: from atom to bedside journal January 2024

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