Efficient preparation of 64Cu and radiolabeling of Nectin-4 antibody for esophageal cancer imaging

Copper-64( ⁶⁴ Cu) is a radioactive isotope used in positron emission tomography (PET) imaging, with promising applications in theranostics. However, the supply of ⁶⁴ Cu is limited and requires significant personnel involvement. To enhance ⁶⁴ Cu yield and minimize personnel exposure, we presented an automated method for producing high-specific-activity ⁶⁴ Cu. Our approach involved the design of a novel electroplating device that employed ⁶⁴Ni as the target material, coupled with an automated system for target dissolution and transfer. Automated ion exchange chromatography was utilized to efficiently purify the dissolved ⁶⁴ Cu, achieving a radionuclide purity of 99.9%. We utilized enriched ⁶⁴ Ni (99.32%) and achieved an electroplating thickness of 60.2–62.2 mg/cm², resulting in a radioactive yield of over 300 mCi. Further synthesis of ⁶⁴ Cu-NOTA-Nectin-4 was carried out, and it was applied to the imaging and biological distribution studies of esophageal squamous cell carcinoma, effectively targeting the tumor site. Leveraging the moderate half-life of ⁶⁴ Cu and its production via medical cyclotrons, this approach enables extended imaging windows, precise tumor localization, providing new insights for the early diagnosis of esophageal cancer in clinical practice.