An automated method for regular productions of copper-64 for PET radiopharmaceuticals

To facilitate the development of PET radiopharmaceuticals labelled with the positron-emitting radioisotope copper-64 (t_1/2 = 12.7 h) we have developed a fully automated method for its regular productions. Using the ⁶⁴Ni(p,n)⁶⁴Cu nuclear reaction applied on a 16.5 MeV PETtrace cyclotron the radioisotope is generated in good yields (up to 2 GBq at end-of-synthesis) within 4 h irradiations on nickel-64 (99.6% enrichment) plated onto a gold disk. Based on ion exchange chromatography an automated method has been devised for efficient extraction of the copper-64 in good radionuclide and chemical purity, with ICP-OES analysis determining the concentration of the copper to be 0.14-1.5 ppm. The specific radioactivities of the copper-64 at end-of-synthesis were calculated to be 9.62-77 GB/μmol. The copper-64 radioisotope obtained from this method was then applied to the radiosynthesis of the hypoxia markers, ⁶⁴Cu-ATSM and ⁶⁴Cu-ATSE, which were obtained in good radiochemical yields of >95%.