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 ([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.
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 [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 draft 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.
Conclusions: We have developed a high-yielding, automated method for the production of very high amounts of [68Ga]GaCl3, sufficient for 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.
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Posted 22 Sep, 2020
On 07 Jan, 2021
On 18 Oct, 2020
Received 02 Oct, 2020
Received 02 Oct, 2020
Invitations sent on 30 Sep, 2020
On 30 Sep, 2020
On 30 Sep, 2020
On 29 Sep, 2020
On 28 Sep, 2020
On 17 Sep, 2020
On 16 Sep, 2020
Multi-curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE
Posted 22 Sep, 2020
On 07 Jan, 2021
On 18 Oct, 2020
Received 02 Oct, 2020
Received 02 Oct, 2020
Invitations sent on 30 Sep, 2020
On 30 Sep, 2020
On 30 Sep, 2020
On 29 Sep, 2020
On 28 Sep, 2020
On 17 Sep, 2020
On 16 Sep, 2020
Background: 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. 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.
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 [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 draft 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.
Conclusions: We have developed a high-yielding, automated method for the production of very high amounts of [68Ga]GaCl3, sufficient for 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.
Figure 1
Figure 2
Figure 3