Establishing reliable Cu-64 production process: From target plating to molecular specific tumor micro-PET imaging

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Abstract

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.

Figures

  • Figure 2. The 64Ni target produced in this study. (a) Photo of the 64Ni target; (b) The SEM image of the 64Ni target; (c) The EDS spectrum of the 64Ni target; (d) The thickness measurement of the 64Ni solid target.
  • Figure 2. The 64Ni target produced in this study. (a) Photo of the 64Ni target; (b) The SEM image of the 64Ni target; (c) The EDS spectrum of the 64Ni target; (d) The thickness measurement of the 64Ni solid target. Figure 2. The 64Ni target produced in this study. (a) Photo of the 64Ni target; (b) The SEM image of the 64Ni target; (c) The EDS spectrum of the 64Ni target; (d) The thickness measurement of the 64Ni solid target.
  • Figure 3. Gamma spectra of 64CuCl2 solution after purification. Figure 3. Gamma spectra of 64CuCl2 solution after purification.
  • Figure 5. Radio-synthesis of 64Cu-DOTA-rituximab. (A) Modification of Rituximab and radiolabeling by 64Cu radionuclide; (B) The Radio-HPLC (radioactive high performance liquid chromatography) chromatograph of rituximab; (C) The Radio-HPLC chromatograph of 64Cu-DOTA-rituximab after purification by PD-10 column; (D) The Radio-TLC (radioactive thin-layer chromatography) image of 64CuCl2; (E) The Radio-TLC image of 64Cu-DOTA-rituximab after purification by PD-10 column.
  • Figure 5. Radio-synthesis of 64Cu-DOTA-rituximab. (A) Modification of Rituximab and radiolabeling by 64Cu radionuclide; (B) The Radio-HPLC (radioactive high performance liquid chromatography) chromatograph of rituximab; (C) The Radio-HPLC chromatograph of 64Cu-DOTA-rituximab after purification by PD-10 column; (D) The Radio-TLC (radioactive thin-layer chromatography) image of 64CuCl2; (E) The Radio-TLC image of 64Cu-DOTA-rituximab after purification by PD-10 column.
  • Figure 6. Micro-PET image of 64Cu-DOTA-rituximab in SCID mice bearing Ramos RA1 tumors at 24 h and 60 h post-intravenous injection. The arrows indicate the location of tumor.
  • Figure 7. Schematic representation of the automated 64Cu separation system. Figure 7. Schematic representation of the auto 4Cu sep ration ystem.

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Xie, Q., Zhu, H., Wang, F., Meng, X., Ren, Q., Xia, C., & Yang, Z. (2017). Establishing reliable Cu-64 production process: From target plating to molecular specific tumor micro-PET imaging. Molecules, 22(4). https://doi.org/10.3390/molecules22040641

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