Abstract
BackgroundWith increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([68Ge]Ge/[68Ga]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 [68Ga]GaCl3 from solid zinc-68 targets and subsequent labelling to produce clinical-grade [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTATATE.ResultsEnriched 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 [68Ga]GaCl3 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 [68Ga]GaCl3 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 [68Ga]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.ConclusionsWe have developed a high-yielding, automated method for the production of very high amounts of [68Ga]GaCl3, 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 [68Ga]GaCl3 for radiolabelling and [68Ga]Ga-PSMA-11 are promising for clinical use.
Highlights
With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([68Ge]Ge/[68Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope
Targetry and [68Ga]GaCl3 productions During beam current ramping experiments, we determined that the zinc targets were capable of withstanding beam currents of at least 80 μA of 13 MeV protons for 2 h, which is equivalent to approximately 1 kW of power deposited in the zinc target material
Irradiations performed under these conditions (80 μA for 120 min) produced up to 194 GBq (5.24 Ci) of purified [68Ga]GaCl3 at the end of purification (EOP) from an expected > 370 GBq (> 10 Ci) gallium-68 at end of bombardment (EOB)
Summary
With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([68Ge]Ge/[68Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. We demonstrate a high-yield, automated method for producing multi-Curie levels of [68Ga]GaCl3 from solid zinc-68 targets and subsequent labelling to produce clinical-grade [68Ga]GaPSMA-11 and [68Ga]Ga-DOTATATE. Generators remained as a reliable method for supplying this PET radionuclide for the development of novel radiotracers and imaging techniques. Direct cyclotron production of gallium-68 using the 68Zn(p,n)68Ga transformation on small medical cyclotrons provides access to clinically relevant quantities of the gallium-68 isotope. Solid targets are more reliable and provide much higher yields, but until recently commercial systems capable of transporting solid targets by remote operation were limited and were not compatible with many selfshielded medical cyclotrons currently installed
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