Abstract 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 ( 76/77 BrRD1). As 77 Brbromide activity in 76/77 BrRD1 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 76/77 Brbromide solution chemistry to enable reproducible production of preclinical quantities of 76/77 BrRD1. 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 76/77 Brbromide elution volume from 2.9 to 0.9 mL. Across all distillations, when 77 Brbromide was isolated in less than 1 mL of QMA eluant, copper-mediated bromodeborylation of a BPin precursor molecule formed 76/77 BrRD1 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 77 BrRD1 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, 76/77 Brbromide production yields from GE PETtrace STP targets agreed with those previously published. The changes described in this work not only aimed to maximize 76/77 Brbromide recovery after distillation, but also chemical reactivity in large-scale 76/77 BrRD1 radiopharmaceutical syntheses. This balancing act resulted in a slightly lower 76/77 Brbromide recovery yield but more consistently 76/77 BrRD1 product yield.
Johnson et al. (Mon,) studied this question.