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

The interest in ⁶²Cu as a tracer for positron emission tomography (PET) has motivated several designs of a ⁶²Zn/⁶²Cu radionuclide generator, the most common of which is based on anion exchange resin and a mixed HCl/NaCl eluent. Since commercial ⁶²Zn/⁶²Cu generators are currently not available, the continued investigation of ⁶²Cu-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 ⁶²Zn/⁶²Cu generators, including loading methodology, eluent composition, column dimensions, and ⁶²Cu activity quantification.

⁶²Zn and the long-lived tracer ⁶⁵Zn were produced via proton irradiation of Cu targets and used to evaluate ⁶²Zn/⁶²Cu 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 ⁶²Zn. 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 ⁶²Cu elution efficiency and zinc breakthrough. The HCl eluent gave comparable ⁶²Cu 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 ⁶²Cu elution efficiencies to 150 mg columns while decreasing zinc breakthrough. Additionally, an improved methodology for ⁶²Cu activity quantification was developed to support reliable generator performance assessment. The produced ⁶²Cu was used to radiolabel diacetyl bis(N⁴-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 ⁶²Zn/⁶²Cu generator systems. The results highlight how these parameters influence zinc breakthrough, ⁶²Cu elution efficiency, and downstream radiolabeling. This study outlines practical and transferable operating considerations that support the implementation of in-house ⁶²Zn/⁶²Cu generator systems, contributing towards a broader availability of ⁶²Cu for future studies.