A comparative evaluation of chemical processes in anion exchange-based 62Zn/62Cu generator systems

The interest in 62 Cu as a tracer for positron emission tomography (PET) has motivated several designs of a 62 Zn/ 62 Cu radionuclide generator, the most common of which is based on anion exchange resin and a mixed HCl/NaCl eluent. Since commercial 62 Zn/ 62 Cu generators are currently not available, the continued investigation of 62 Cu-based radiopharmaceuticals relies on the implementation of in-house generator systems. This work presents a systematic evaluation of several key parameters relevant to anion exchange-based 62 Zn/ 62 Cu generators, including loading methodology, eluent composition, column dimensions, and 62 Cu activity quantification. 62 Zn and the long-lived tracer 65 Zn were produced via proton irradiation of Cu targets and used to evaluate 62 Zn/ 62 Cu generator performance. A simplified target processing method was developed for generator manufacturing, representing a practical approach for handling irradiated targets given the 9.2 h half-life of 62 Zn. Two generator loading approaches were compared, batch loading and fixed-bed loading. Fixed-bed loading yielded significantly lower zinc breakthrough than batch loading, with 1.1(2) × 10 –3 % compared to 20.6(1)% zinc eluted in the first 20 mL, while maintaining similar loading times. The commonly used 0.2 M HCl/1.8 M NaCl eluent was compared with 2 M HCl to assess the influence of eluent composition on 62 Cu elution efficiency and zinc breakthrough. The HCl eluent gave comparable 62 Cu elution efficiency, achieving an 84(4)% yield in a 1 mL elution, and lower zinc breakthrough. Resin mass was also evaluated, with 200 mg columns providing similar 62 Cu elution efficiencies to 150 mg columns while decreasing zinc breakthrough. Additionally, an improved methodology for 62 Cu activity quantification was developed to support reliable generator performance assessment. The produced 62 Cu was used to radiolabel diacetyl bis(N 4 -methylthiosemicarbazone) (ATSM) at high yield in both eluents and used in a proof-of-principal PET imaging study of a tumor-bearing mouse. This study provides a comparison of loading method, eluent composition, and column configuration in anion exchange-based 62 Zn/ 62 Cu generator systems. The results highlight how these parameters influence zinc breakthrough, 62 Cu elution efficiency, and downstream radiolabeling. This study outlines practical and transferable operating considerations that support the implementation of in-house 62 Zn/ 62 Cu generator systems, contributing towards a broader availability of 62 Cu for future studies.