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Title: Improved production of 76Br, 77Br and 80mBr via CoSe cyclotron targets and vertical dry distillation

Abstract

The radioisotopes of bromine are uniquely suitable radiolabels for small molecule theranostic radiopharmaceuticals but are of limited availability due to production challenges. Significantly improved methods were developed for the production and radiochemical isolation of clinical quality 76Br, 77Br, and 80mBr. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel 77Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein. 76Br, 77Br, and 80mBr were produced in high radionuclidic purity via the proton irradiation of novel isotopically-enriched Co76Se, Co77Se, and Co80Se intermetallic targets, respectively. Radiobromine was isolated through thermal chromatographic distillation in a vertical furnace assembly. The 77Br-labeled PARP inhibitor was synthesized via copper-mediated aryl boronic ester radiobromination. Cyclotron production yields were 103 ± 10 MBq∙μA–1∙h–1 for 76Br, 88 ± 10 MBq∙μA–1∙h–1 for 80mBr at 16 MeV and 17 ± 1 MBq∙μA–1∙h–1 for 77Br at 13 MeV. Radiobromide isolation yields were 76 ± 11% in a small volume of aqueous solution. The synthesized 77Br-labeled PARP-1 inhibitor had a measured apparent molar activity up to 700 GBq/μmol at end of synthesis. A novel selenium alloy target enabled clinical-scale production of 76Br, 77Br, and 80mBr with high apparent molar activities, which wasmore » used to for the production of a new 77Br-labeled inhibitor of PARP-1. Here, new methods for the cyclotron production and isolation of radiobromine improved the production capacity of 77Br by a factor of three and 76Br by a factor of six compared with previous methods. Preclinical translational research of 77Br-based Auger electron radiotherapeutics, such as those targeting PARP-1, will require the production of GBq-scale 77Br, which necessitates next-generation, high-yielding, isotopically-enriched cyclotron targets, such as the novel intermetallic Co77Se.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [2];  [3];  [1];  [1];  [3];  [1];  [1];  [2];  [1]
  1. Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States)
  2. Univ. of Pennsylvania, Philadelphia, PA (United States)
  3. Univ. of Alabama at Birmingham, AL (United States)
Publication Date:
Research Org.:
Univ. of Wisconsin-Madison, WI (United States); Univ. of Alabama at Birmingham, AL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Nuclear Physics (NP)
OSTI Identifier:
1804870
Alternate Identifier(s):
OSTI ID: 1602292
Grant/Contract Number:  
SC0017919; SC0017912
Resource Type:
Accepted Manuscript
Journal Name:
Nuclear Medicine and Biology
Additional Journal Information:
Journal Volume: 80-81; Journal ID: ISSN 0969-8051
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; Bromine-77; Bromine-76; Bromine-80 m; Auger radionuclide therapy; Positron emission tomography; PARP-1 inhibitor

Citation Formats

Ellison, Paul A., Olson, Aeli P., Barnhart, Todd E., Hoffman, Sabrina L. V., Reilly, Sean W., Makvandi, Mehran, Bartels, Jennifer L., Murali, Dhanabalan, DeJesus, Onofre T., Lapi, Suzanne E., Bednarz, Bryan, Nickles, Robert J., Mach, Robert H., and Engle, Jonathan W. Improved production of 76Br, 77Br and 80mBr via CoSe cyclotron targets and vertical dry distillation. United States: N. p., 2019. Web. doi:10.1016/j.nucmedbio.2019.09.001.
Ellison, Paul A., Olson, Aeli P., Barnhart, Todd E., Hoffman, Sabrina L. V., Reilly, Sean W., Makvandi, Mehran, Bartels, Jennifer L., Murali, Dhanabalan, DeJesus, Onofre T., Lapi, Suzanne E., Bednarz, Bryan, Nickles, Robert J., Mach, Robert H., & Engle, Jonathan W. Improved production of 76Br, 77Br and 80mBr via CoSe cyclotron targets and vertical dry distillation. United States. https://doi.org/10.1016/j.nucmedbio.2019.09.001
Ellison, Paul A., Olson, Aeli P., Barnhart, Todd E., Hoffman, Sabrina L. V., Reilly, Sean W., Makvandi, Mehran, Bartels, Jennifer L., Murali, Dhanabalan, DeJesus, Onofre T., Lapi, Suzanne E., Bednarz, Bryan, Nickles, Robert J., Mach, Robert H., and Engle, Jonathan W. Thu . "Improved production of 76Br, 77Br and 80mBr via CoSe cyclotron targets and vertical dry distillation". United States. https://doi.org/10.1016/j.nucmedbio.2019.09.001. https://www.osti.gov/servlets/purl/1804870.
@article{osti_1804870,
title = {Improved production of 76Br, 77Br and 80mBr via CoSe cyclotron targets and vertical dry distillation},
author = {Ellison, Paul A. and Olson, Aeli P. and Barnhart, Todd E. and Hoffman, Sabrina L. V. and Reilly, Sean W. and Makvandi, Mehran and Bartels, Jennifer L. and Murali, Dhanabalan and DeJesus, Onofre T. and Lapi, Suzanne E. and Bednarz, Bryan and Nickles, Robert J. and Mach, Robert H. and Engle, Jonathan W.},
abstractNote = {The radioisotopes of bromine are uniquely suitable radiolabels for small molecule theranostic radiopharmaceuticals but are of limited availability due to production challenges. Significantly improved methods were developed for the production and radiochemical isolation of clinical quality 76Br, 77Br, and 80mBr. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel 77Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein. 76Br, 77Br, and 80mBr were produced in high radionuclidic purity via the proton irradiation of novel isotopically-enriched Co76Se, Co77Se, and Co80Se intermetallic targets, respectively. Radiobromine was isolated through thermal chromatographic distillation in a vertical furnace assembly. The 77Br-labeled PARP inhibitor was synthesized via copper-mediated aryl boronic ester radiobromination. Cyclotron production yields were 103 ± 10 MBq∙μA–1∙h–1 for 76Br, 88 ± 10 MBq∙μA–1∙h–1 for 80mBr at 16 MeV and 17 ± 1 MBq∙μA–1∙h–1 for 77Br at 13 MeV. Radiobromide isolation yields were 76 ± 11% in a small volume of aqueous solution. The synthesized 77Br-labeled PARP-1 inhibitor had a measured apparent molar activity up to 700 GBq/μmol at end of synthesis. A novel selenium alloy target enabled clinical-scale production of 76Br, 77Br, and 80mBr with high apparent molar activities, which was used to for the production of a new 77Br-labeled inhibitor of PARP-1. Here, new methods for the cyclotron production and isolation of radiobromine improved the production capacity of 77Br by a factor of three and 76Br by a factor of six compared with previous methods. Preclinical translational research of 77Br-based Auger electron radiotherapeutics, such as those targeting PARP-1, will require the production of GBq-scale 77Br, which necessitates next-generation, high-yielding, isotopically-enriched cyclotron targets, such as the novel intermetallic Co77Se.},
doi = {10.1016/j.nucmedbio.2019.09.001},
journal = {Nuclear Medicine and Biology},
number = ,
volume = 80-81,
place = {United States},
year = {Thu Sep 05 00:00:00 EDT 2019},
month = {Thu Sep 05 00:00:00 EDT 2019}
}

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