Improved production of Br, Br and 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 Br, Br, and Br. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein.

Methods: Br, Br, and Br were produced in high radionuclidic purity via the proton irradiation of novel isotopically-enriched CoSe, CoSe, and CoSe intermetallic targets, respectively. Radiobromine was isolated through thermal chromatographic distillation in a vertical furnace assembly. The Br-labeled PARP inhibitor was synthesized via copper-mediated aryl boronic ester radiobromination.

Results: Cyclotron production yields were 103 ± 10 MBq∙μA∙h for Br, 88 ± 10 MBq∙μA∙h for Br at 16 MeV and 17 ± 1 MBq∙μA∙h for Br at 13 MeV. Radiobromide isolation yields were 76 ± 11% in a small volume of aqueous solution. The synthesized 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 Br, Br, and Br with high apparent molar activities, which was used to for the production of a new Br-labeled inhibitor of PARP-1.

Advances In Knowledge: New methods for the cyclotron production and isolation of radiobromine improved the production capacity of Br by a factor of three and Br by a factor of six compared with previous methods.

Implications For Patient Care: Preclinical translational research of Br-based Auger electron radiotherapeutics, such as those targeting PARP-1, will require the production of GBq-scale Br, which necessitates next-generation, high-yielding, isotopically-enriched cyclotron targets, such as the novel intermetallic CoSe.