Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE

Helge Thisgaard; Joel Kumlin; Niels Langkjær; Jansen Chua; Brian Hook; Mikael Jensen; Amir Kassaian; Stefan Zeisler; Sogol Borjian; Michael Cross; Paul Schaffer; Johan Hygum Dam

doi:10.1186/s41181-020-00114-9

Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE

EJNMMI Radiopharm Chem. 2021 Jan 7;6(1):1. doi: 10.1186/s41181-020-00114-9.

Authors

Helge Thisgaard^{1

2}, Joel Kumlin³, Niels Langkjær⁴, Jansen Chua³, Brian Hook³, Mikael Jensen⁵, Amir Kassaian³, Stefan Zeisler³, Sogol Borjian³, Michael Cross³, Paul Schaffer^{3

6}, Johan Hygum Dam^{4

7}

Affiliations

¹ Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, 5000, Odense, Denmark. helge.thisgaard@rsyd.dk.
² Department of Clinical Research, University of Southern Denmark, Odense, Denmark. helge.thisgaard@rsyd.dk.
³ ARTMS, Vancouver, BC, Canada.
⁴ Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, 5000, Odense, Denmark.
⁵ The Hevesy Laboratory, Health Technology, Technical University of Denmark, Roskilde, Denmark.
⁶ Life Sciences, TRIUMF, Vancouver, BC, Canada.
⁷ Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Abstract

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 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 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.

Keywords: Accelerator; Cyclotron; DOTATATE; Gallium-68; PSMA-11; Solid target; Targetry.