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. 2017 Apr 17;22(4):641.
doi: 10.3390/molecules22040641.

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

Qinghua Xie  1   2 , Hua Zhu  3 , Feng Wang  4 , Xiangxi Meng  5 , Qiushi Ren  6 , Chuanqin Xia  7 , Zhi Yang  8
Affiliations

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

Qinghua Xie et al. Molecules. .

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.

Keywords: Rituximab; copper-64; positron emission tomography (PET); solid target.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The 64Ni plating vessel. (a) Illustration of new 64Ni plating vessel by scheme; (b) Picture of the actual electric plating unit.
Figure 2
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
Figure 3
Gamma spectra of 64CuCl2 solution after purification.
Figure 4
Figure 4
The radioactivity of the produced 64Cu measured at different time points vs. time, with fitted equation, on a logarithmic scale.
Figure 5
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
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
Figure 7
Schematic representation of the automated 64Cu separation system.
See this image and copyright information in PMC

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