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Title: Large-Scale Production of 119m Te and 119 Sb for Radiopharmaceutical Applications

Abstract

Radionuclides find widespread use in medical technologies for treating and diagnosing disease. Among successful and emerging radiotherapeutics, 119Sb has unique potential in targeted therapeutic applications for low-energy electron-emitting isotopes. Unfortunately, developing 119Sb-based drugs has been slow in comparison to other radionuclides, primarily due to limited accessibility. Herein is a production method that overcomes this challenge and expands the available time for large-scale distribution and use. Our approach exploits high flux and fluence from high-energy proton sources to produce longer lived 119mTe. This parent isotope slowly decays to 119Sb, which in turn provides access to 119Sb for longer time periods (in comparison to direct 119Sb production routes). We contribute the target design, irradiation conditions, and a rapid procedure for isolating the 119mTe/119Sb pair. To guide process development and to understand why the procedure was successful, we characterized the Te/Sb separation using Te and Sb K-edge X-ray absorption spectroscopy. The procedure provides low-volume aqueous solutions that have high 119mTe and consequently 119Sb specific activity in a chemically pure form. This procedure has been demonstrated at large-scale (production-sized, Ci quantities), and the product has potential to meet stringent Food and Drug Administration requirements for a 119mTe/119Sb active pharmaceutical ingredient.

Authors:
ORCiD logo [1]; ORCiD logo [1];  [1];  [1];  [2];  [1]; ORCiD logo [3];  [4];  [1]; ORCiD logo [1]; ORCiD logo [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States
  2. Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States, University of Iowa, Iowa City, Iowa 52242-1294, United States
  3. University of Iowa, Iowa City, Iowa 52242-1294, United States
  4. Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States, University of Wisconsin, Madison, Wisconsin 53705, United States
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1496496
Alternate Identifier(s):
OSTI ID: 1499362; OSTI ID: 1512781
Report Number(s):
LA-UR-18-31048
Journal ID: ISSN 2374-7943
Grant/Contract Number:  
89233218CNA000001; SC141099; AC02-76SF00515
Resource Type:
Journal Article: Published Article
Journal Name:
ACS Central Science
Additional Journal Information:
Journal Name: ACS Central Science; Journal ID: ISSN 2374-7943
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY

Citation Formats

Bennett, Kevin T., Bone, Sharon E., Akin, Andrew C., Birnbaum, Eva R., Blake, Anastasia V., Brugh, Mark, Daly, Scott R., Engle, Jonathan W., Fassbender, Michael E., Ferrier, Maryline G., Kozimor, Stosh A., Lilley, Laura M., Martinez, Christopher A., Mocko, Veronika, Nortier, Francois M., Stein, Benjamin W., Thiemann, Sara L., and Vermeulen, Christiaan. Large-Scale Production of 119m Te and 119 Sb for Radiopharmaceutical Applications. United States: N. p., 2019. Web. doi:10.1021/acscentsci.8b00869.
Bennett, Kevin T., Bone, Sharon E., Akin, Andrew C., Birnbaum, Eva R., Blake, Anastasia V., Brugh, Mark, Daly, Scott R., Engle, Jonathan W., Fassbender, Michael E., Ferrier, Maryline G., Kozimor, Stosh A., Lilley, Laura M., Martinez, Christopher A., Mocko, Veronika, Nortier, Francois M., Stein, Benjamin W., Thiemann, Sara L., & Vermeulen, Christiaan. Large-Scale Production of 119m Te and 119 Sb for Radiopharmaceutical Applications. United States. https://doi.org/10.1021/acscentsci.8b00869
Bennett, Kevin T., Bone, Sharon E., Akin, Andrew C., Birnbaum, Eva R., Blake, Anastasia V., Brugh, Mark, Daly, Scott R., Engle, Jonathan W., Fassbender, Michael E., Ferrier, Maryline G., Kozimor, Stosh A., Lilley, Laura M., Martinez, Christopher A., Mocko, Veronika, Nortier, Francois M., Stein, Benjamin W., Thiemann, Sara L., and Vermeulen, Christiaan. 2019. "Large-Scale Production of 119m Te and 119 Sb for Radiopharmaceutical Applications". United States. https://doi.org/10.1021/acscentsci.8b00869.
@article{osti_1496496,
title = {Large-Scale Production of 119m Te and 119 Sb for Radiopharmaceutical Applications},
author = {Bennett, Kevin T. and Bone, Sharon E. and Akin, Andrew C. and Birnbaum, Eva R. and Blake, Anastasia V. and Brugh, Mark and Daly, Scott R. and Engle, Jonathan W. and Fassbender, Michael E. and Ferrier, Maryline G. and Kozimor, Stosh A. and Lilley, Laura M. and Martinez, Christopher A. and Mocko, Veronika and Nortier, Francois M. and Stein, Benjamin W. and Thiemann, Sara L. and Vermeulen, Christiaan},
abstractNote = {Radionuclides find widespread use in medical technologies for treating and diagnosing disease. Among successful and emerging radiotherapeutics, 119Sb has unique potential in targeted therapeutic applications for low-energy electron-emitting isotopes. Unfortunately, developing 119Sb-based drugs has been slow in comparison to other radionuclides, primarily due to limited accessibility. Herein is a production method that overcomes this challenge and expands the available time for large-scale distribution and use. Our approach exploits high flux and fluence from high-energy proton sources to produce longer lived 119mTe. This parent isotope slowly decays to 119Sb, which in turn provides access to 119Sb for longer time periods (in comparison to direct 119Sb production routes). We contribute the target design, irradiation conditions, and a rapid procedure for isolating the 119mTe/119Sb pair. To guide process development and to understand why the procedure was successful, we characterized the Te/Sb separation using Te and Sb K-edge X-ray absorption spectroscopy. The procedure provides low-volume aqueous solutions that have high 119mTe and consequently 119Sb specific activity in a chemically pure form. This procedure has been demonstrated at large-scale (production-sized, Ci quantities), and the product has potential to meet stringent Food and Drug Administration requirements for a 119mTe/119Sb active pharmaceutical ingredient.},
doi = {10.1021/acscentsci.8b00869},
url = {https://www.osti.gov/biblio/1496496}, journal = {ACS Central Science},
issn = {2374-7943},
number = ,
volume = ,
place = {United States},
year = {Mon Feb 25 00:00:00 EST 2019},
month = {Mon Feb 25 00:00:00 EST 2019}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at https://doi.org/10.1021/acscentsci.8b00869

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Cited by: 10 works
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