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

ABSTRACT:

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 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.

Methods

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.

Results

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.

Conclusions

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.

Advances in knowledge

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.

Implications for patient care

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.

SUBMITTER: Ellison PA 

PROVIDER: S-EPMC9066421 | biostudies-literature | 2020 Jan - Feb

REPOSITORIES: biostudies-literature