Background Bromine-76, a positron emitting radionuclide for positron emission tomography (PET) imaging, and bromine-77, an Auger electron (Ae) emitting radionuclide, make a unique halogen theranostic pair. These isotopes have previously been used to synthesize a rucaparib-derived, poly-ADP-ribose polymerase inhibitor ([76/77Br]RD1). As [77Br]bromide activity in [76/77Br]RD1 radiosyntheses increased, coincident with solid target hardware changes in our facility, radiopharmaceutical yield became less reproducible. This work describes the modifications to this hardware, distillation procedures, and [76/77Br]bromide solution chemistry to enable reproducible production of preclinical quantities of [76/77Br]RD1. Results Isotopically enriched cobalt selenide targets had production yields of 50.7 ± 8.7 MBq/µAh for bromine-76 and 14.5 ± 3.3 MBq/µAh for bromine-77, consistent with previous reports. Adoption of the GE PETtrace Solid Target Platform (STP) increased target backing diameter to 22 mm. Increasing dry distillation duration from 5 to 6 min to 8–9 min and furnace temperature from 1050 to 1055 °C released 94 ± 5% (n = 17) of activity, in agreement with previous smaller targets (92 ± 13%, n = 35). Rinsing glassware and loading the quaternary methyl ammonium (QMA) anion exchange cartridge in 1 mM sodium bicarbonate reduced [76/77Br]bromide elution volume from 2.9 to 0.9 mL. Across all distillations, when [77Br]bromide was isolated in less than 1 mL of QMA eluant, copper-mediated bromodeborylation of a BPin precursor molecule formed [76/77Br]RD1 with a radiochemical conversion of 98 ± 3% (n = 17) and overall radiopharmaceutical yield of 70 ± 10% (n = 15) following purification and final formulation. Up to 580 MBq of purified [77Br]RD1 have been produced with this system. Conclusion The new target production technique made targets suitable for long-term use with the GE PETtrace STP. Following modifications to the distillation process, [76/77Br]bromide production yields from GE PETtrace STP targets agreed with those previously published. The changes described in this work not only aimed to maximize [76/77Br]bromide recovery after distillation, but also chemical reactivity in large-scale [76/77Br]RD1 radiopharmaceutical syntheses. This balancing act resulted in a slightly lower [76/77Br]bromide recovery yield but more consistently [76/77Br]RD1 product yield.

Scaling the production of bromine-76 and bromine-77 labeled poly-ADP-ribose-polymerase-targeted theranostics for preclinical use

期刊论文
出版模式：

开放获取
发表日期：

2026年6月1日

查看全文

Taylor R. Johnson,
Hong Beom Lee,
Yngve Guttormsen,
Jason C. Mixdorf,
Todd E. Barnhart,
Jonathan W. Engle,
Paul A. Ellison

摘要

Background

Bromine-76, a positron emitting radionuclide for positron emission tomography (PET) imaging, and bromine-77, an Auger electron (Ae) emitting radionuclide, make a unique halogen theranostic pair. These isotopes have previously been used to synthesize a rucaparib-derived, poly-ADP-ribose polymerase inhibitor ([^76/77Br]RD1). As [⁷⁷Br]bromide activity in [^76/77Br]RD1 radiosyntheses increased, coincident with solid target hardware changes in our facility, radiopharmaceutical yield became less reproducible. This work describes the modifications to this hardware, distillation procedures, and [^76/77Br]bromide solution chemistry to enable reproducible production of preclinical quantities of [^76/77Br]RD1.

Results

Isotopically enriched cobalt selenide targets had production yields of 50.7 ± 8.7 MBq/µAh for bromine-76 and 14.5 ± 3.3 MBq/µAh for bromine-77, consistent with previous reports. Adoption of the GE PETtrace Solid Target Platform (STP) increased target backing diameter to 22 mm. Increasing dry distillation duration from 5 to 6 min to 8–9 min and furnace temperature from 1050 to 1055 °C released 94 ± 5% (n = 17) of activity, in agreement with previous smaller targets (92 ± 13%, n = 35). Rinsing glassware and loading the quaternary methyl ammonium (QMA) anion exchange cartridge in 1 mM sodium bicarbonate reduced [^76/77Br]bromide elution volume from 2.9 to 0.9 mL. Across all distillations, when [⁷⁷Br]bromide was isolated in less than 1 mL of QMA eluant, copper-mediated bromodeborylation of a BPin precursor molecule formed [^76/77Br]RD1 with a radiochemical conversion of 98 ± 3% (n = 17) and overall radiopharmaceutical yield of 70 ± 10% (n = 15) following purification and final formulation. Up to 580 MBq of purified [⁷⁷Br]RD1 have been produced with this system.

Conclusion

The new target production technique made targets suitable for long-term use with the GE PETtrace STP. Following modifications to the distillation process, [^76/77Br]bromide production yields from GE PETtrace STP targets agreed with those previously published. The changes described in this work not only aimed to maximize [^76/77Br]bromide recovery after distillation, but also chemical reactivity in large-scale [^76/77Br]RD1 radiopharmaceutical syntheses. This balancing act resulted in a slightly lower [^76/77Br]bromide recovery yield but more consistently [^76/77Br]RD1 product yield.