Multi-curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Background: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([Ge]Ge/[Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [Ga]GaCl from solid zinc-68 targets and subsequent labelling to produce clinical-grade [Ga]Ga-PSMA-11 and [Ga]Ga-DOTATATE.

Results: Enriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.24 Ci) of purified gallium-68 in the form of [Ga]GaCl at the end of purification (EOP) from an expected > 370 GBq (> 10 Ci) at end of bombardment. A fully automated dissolution/separation process was completed in 35 min. Isolated product was analysed according to the Ph. Eur. monograph for accelerator produced [Ga]GaCl and found to comply with all specifications. In every instance, the radiochemical purity exceeded 99.9% and importantly, the radionuclidic purity was sufficient to allow for a shelf-life of up to 7 h based on this metric alone. Fully automated production of up to 72.2 GBq [Ga]Ga-PSMA-11 was performed, providing a product with high radiochemical purity (> 98.2%) and very high apparent molar activities of up to 722 MBq/nmol. Further, manual radiolabelling of up to 3.2 GBq DOTATATE was performed in high yields (> 95%) and with apparent molar activities (9-25 MBq/nmol) sufficient for clinical use.

Conclusions: We have developed a high-yielding, automated method for the production of very high amounts of [Ga]GaCl, sufficient to supply proximal radiopharmacies. The reported method led to record-high purified gallium-68 activities (194 GBq at end of purification) and subsequent labelling of PSMA-11 and DOTATATE. The process was highly automated from irradiation through to formulation of the product, and as such comprised a high level of radiation protection. The quality control results obtained for both [Ga]GaCl for radiolabelling and [Ga]Ga-PSMA-11 are promising for clinical use.