Establishing Reliable Cu-64 Production Process: From Target Plating to Molecular Specific Tumor Micro-PET Imaging

Copper-64 is a useful radioisotope for positron emission tomography (PET). Due to the wide range of applications, the demand of ⁶⁴Cu with low metallic impurities is increasing. Here we report a simple method for the efficient production of high specific activity ⁶⁴Cu using a cyclotron for biomedical application. We designed new equipment based on the plating of enriched ⁶⁴Ni as the target, and used automated ion exchange chromatography to purify copper-64 efficiently after irradiation and dissolution of the target in good radiochemical and chemical yield and purity. The ⁶⁴Cu radionuclide produced using 99.32% enriched ⁶⁴Ni with a density of 61.4 ± 5.0 mg/cm², reaching a total radioactivity greater than 200 mCi, with specific activity up to 5.6 GBq/μmoL. It was further incorporated into modified monoclonal antibody DOTA-rituximab to synthesize ⁶⁴Cu-DOTA-rituximab, which was used successfully for micro-PET imaging.