Introduction: The commissioning of the Royal Darwin Hospital (RDH) Cyclotron Facility in 2022 provided Northern Territorians with greater access to clinical PET radiopharmaceuticals. Producing [18F]FDG since inception, the facility has the onsite capability to manufacture a suite of PET radiopharmaceuticals, including those including cyclotron-produced radionuclides other than [18F]F-. Given emerging trends in PET radionuclide production, constraints in the supply of key starting materials (e.g 68Ge) and evolving cyclotron target technologies (68Ga solid and liquid targetry), the production of radionuclides such as [68Ga]Ga3+ by cyclotron bombardment at RDH has the potential to leverage the facility’s capabilities efficiently for the broad and dispersed population of the Northern Territory. This study describes the investigation and validation of [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTA-TATE, prepared using accelerator-produced [68Ga]Ga3+. In this study, [68Ga]Ga3+ was manufactured using an IBA Kiube 100 18 MeV cyclotron, with target purification and radiosynthesis performed using IBA Synthera Extension and Synthera+ modules respectively.
Methods: Production and purification of [68Ga]Ga3+ was performed using 68Zn(NO3)2) target solution (0.5 M - 1.0 M; Fluidomica) and the IBA Nirta liquid target system on the IBA Kiube 100 cyclotron (with beam degradation), with beam time, target current and target volume evaluated. Using the Fluidomica [68Ga]Ga3+ purification kit, conditions were optimised and evaluated for purified [68Ga]GaCl3 with respect to radioactivity distribution, separation of metal impurities and radionuclidic purity. Radiosynthesis conditions were optimised for the manufacture of [68Ga]GaPSMA-11 for the reaction buffer (HEPES, NaOAc) and radiolabelling, stabilizer concentration and process efficiency. Radiosynthesis conditions were also confirmed for the manufacture of [68Ga]GaDOTA-TATE, and validation of both [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTA-TATE were performed.
Results: Optimised bombardment of 68Zn(NO3)2) target solution, and liquid target purification of [68Ga]Ga3+ produced [68Ga]GaCl3 in activities ranging from 1.8 – 2.0 GBq (0.5 M) and 3.6 – 4.4 GBq (1.0 M) at End of Purification (EOP). Key metrics for metal impurities (Fe/Zn <3 μg/GBq @ EOP) and Radionuclidic Purity (98% 68Ga content 3hrs after EOP; <0.1% impurities) were in line with CQA’s for accelerator-produced [68Ga]GaCl3 defined in Ph. Eur. Monograph 3109. [68Ga]GaPSMA-11 and [68Ga]GaDOTA-TATE prepared from accelerator-produced [68Ga]GaCl3 (from 0.5 M 68Zn(NO3)2 target solution), yielded activities ranging from 1.09 – 1.45 GBq (PSMA) and 1.06 – 1.36 GBq (DOTA-TATE) at End of Synthesis (EOS). Subsequent scale up (to 1.0 M 68Zn(NO3)2) furnished 2.31 – 2.37 GBq (PSMA) and 2.00 – 2.40 GBq (DOTA-TATE) at EOS. All validation batches conformed with Quality Control testing performed (including for [68Ga]Ga-PSMA-11; to Ph. Eur. Monograph 3044), and were suitably stable by TLC and HPLC (RCP >96% at >3h after EOP).
Conclusions: Evaluation of the production of [68Ga]Ga-PSMA-11 and [68Ga]GaDOTA-TATE using accelerator-produced [68Ga]GaCl3 resulted in finished products that met key quality requirements for clinical use. This methodology is currently being used clinically to support patients being evaluated for prostate cancer and neuroendocrine cancers in the Northern Territory.