Improved production of 76 Br, 77 Br and 80m Br via CoSe cyclotron targets and vertical dry distillation.

Introduction: 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 ⁷⁶ Br, ⁷⁷ Br, and ^80m Br. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel ⁷⁷ Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein.
Methods: ⁷⁶ Br, ⁷⁷ Br, and ^80m Br were produced in high radionuclidic purity via the proton irradiation of novel isotopically-enriched Co ⁷⁶ Se, Co ⁷⁷ Se, and Co ⁸⁰ Se intermetallic targets, respectively. Radiobromine was isolated through thermal chromatographic distillation in a vertical furnace assembly. The ⁷⁷ Br-labeled PARP inhibitor was synthesized via copper-mediated aryl boronic ester radiobromination.
Results: Cyclotron production yields were 103 ± 10 MBq∙μA ^-1 ∙h ^-1 for ⁷⁶ Br, 88 ± 10 MBq∙μA ^-1 ∙h ^-1 for ^80m Br at 16 MeV and 17 ± 1 MBq∙μA ^-1 ∙h ^-1 for ⁷⁷ Br at 13 MeV. Radiobromide isolation yields were 76 ± 11% in a small volume of aqueous solution. The synthesized ⁷⁷ Br-labeled PARP-1 inhibitor had a measured apparent molar activity up to 700 GBq/μmol at end of synthesis.
Conclusions: A novel selenium alloy target enabled clinical-scale production of ⁷⁶ Br, ⁷⁷ Br, and ^80m Br with high apparent molar activities, which was used to for the production of a new ⁷⁷ Br-labeled inhibitor of PARP-1.
Advances in Knowledge: New methods for the cyclotron production and isolation of radiobromine improved the production capacity of ⁷⁷ Br by a factor of three and ⁷⁶ Br by a factor of six compared with previous methods.
Implications for Patient Care: Preclinical translational research of ⁷⁷ Br-based Auger electron radiotherapeutics, such as those targeting PARP-1, will require the production of GBq-scale ⁷⁷ Br, which necessitates next-generation, high-yielding, isotopically-enriched cyclotron targets, such as the novel intermetallic Co ⁷⁷ Se.
Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article exist.
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