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

Journal Article · · Nuclear Medicine and Biology
 [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)
+ Show Author Affiliations

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.

Research Organization:
Univ. of Wisconsin-Madison, WI (United States); Univ. of Alabama at Birmingham, AL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Nuclear Physics (NP)
Grant/Contract Number:
SC0017919; SC0017912
OSTI ID:
1804870
Alternate ID(s):
OSTI ID: 1602292
Journal Information:
Nuclear Medicine and Biology, Vol. 80-81; ISSN 0969-8051
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 10 works
Citation information provided by
Web of Science

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Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
Bromine-77
Bromine-76
Bromine-80 m
Auger radionuclide therapy
Positron emission tomography
PARP-1 inhibitor