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Heavy-ion production of ⁷⁷Br and ⁷⁶Br.

ABSTRACT: Many radioisotopes with potential medical applications are difficult to produce routinely, especially those on the proton-rich side of the valley of stability. Current production methods typically use light-ion (protons or deuteron) reactions on materials of similar mass to the target radioisotope, which limits the elemental target material available and may require the use of targets with poor thermal properties (as is the case for the production of radiobromine). These reactions may also create significant amounts of proton-rich decay products which require chemical separation from the desired product in a highly radioactive environment. A promising alternative method using heavy-ion fusion-evaporation reactions for the production of the medically relevant bromine radioisotopes ⁷⁶Br (t_1/2 = 16.2 h) and ⁷⁷Br (t_1/2 = 57.0 h) is presented. Heavy-ion beams of ²⁸Si and ¹⁶O were used to bombard natural chromium and copper targets just above the Coulomb barrier at the University of Notre Dame's Nuclear Science Laboratory to produce these bromine and precursor radioisotopes by fusion-evaporation reactions. Production yields for these reactions were measured and compared to PACE4 calculations. In addition to using more robust targets for irradiation, a simple physical-chemical separation method is proposed that will lead to very high radiopurity yields. A summary of accelerator facility requirements needed for routine production of these radioisotopes is also presented.

SUBMITTER: McGuinness SR

PROVIDER: S-EPMC8333326 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThe 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.Methods76Br, 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.ResultsCyclotron 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.ConclusionsA 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 knowledgeNew 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 carePreclinical 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.

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Heavy-ion production of ⁷⁷Br and ⁷⁶Br.

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Heavy-ion production of 77Br and 76Br.

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Heavy-ion production of ⁷⁷Br and ⁷⁶Br.