GMP-Automated Purification of Copper-61 Produced in Cyclotron Liquid Targets: Methodological Aspects

Background: Expanding the range of metal-based PET radiopharmaceuticals that can be produced by the widely available network of biomedical cyclotrons is a major priority. Copper- 61 is a positron emitter with very favourable physical (61.5% β+, 1.22 MeV max.) and chemical properties, which emerged as a promising PET imaging agent. Objectives: This work aimed to develop and optimise a GMP-automated purification method for copper-61 produced in a cyclotron using a natural zinc liquid target. Methods: The automated purification process was performed using a commercially available Synthera ® Extension module (IBA, Louvain-la-Neuve, Belgium) using a three-column method: two extraction chromatographic resins and a strong anion exchange resin. The final product was evaluated using HPGe and ICP-MS analysis, to assess the radionuclidic and chemical purity of the final copper- 61 solution. Results: The automated purification process was completed within 1 h of processing time, with an average yield of 63.0 ± 15.0%, in a maximum volume of 5 mL. The radionuclidic purity of copper- 61 in the final solution was over 95% for 7 h after EOB. ICP-MS analysis revealed 4.8 ± 2.4 μg of natural zinc in the final purified sample, and the copper-61 molar activity was 230.5 ± 139.3 GBq/μmol. Conclusion: The described purification process allows for the production of a highly radionuclidically and chemically pure, GMP compliant copper-61 solution, ready to be used for the development of copper-61 based radiopharmaceuticals for routine clinical use.