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.
Highlights
Copper-64 (64 Cu) is an attractive radionuclide of considerable interest for positron emission tomography (PET) imaging and radiotherapy due to its intrinsic physical and chemical properties.It has high spatial resolution comparable to 18 F radionuclide, with comparable average free travel distance for their generated positrons (Rave. (β+ ) = 0.70 and 0.69 mm, respectively), due to their comparable positron energy (0.656 MeV and 0.635 MeV, respectively) [1,2]
64 Cu emits β− and Auger electrons, enabling it to be useful for both PET imaging and radiotherapy
The versatile coordination chemistry of 64 Cu allows for its reaction with a wide variety of chelator systems, such as DOTA, NOTA, TETA and CB-TE2A, that can be linked to antibodies, peptides and nanoparticles [3]
Summary
Copper-64 (64 Cu) is an attractive radionuclide of considerable interest for positron emission tomography (PET) imaging and radiotherapy due to its intrinsic physical and chemical properties. Among the nuclear reactions examined, the 64 Ni (p, n) 64 Cu method is the best and widely used, since high production yield of the 64 Cu can be obtained with low energy protons in this route [20,21]. At Washington University, an effective method was investigated to produce high specific activity 64 Cu on a small biomedical cyclotron using the 64 Ni (p, n) 64 Cu nuclear reaction, and 64 Cu has been produced for more than 17 years by the irradiation of electroplated enriched 64 Ni targets in this center [20,22]. At the University of Wisconsin, 64 Cu and 61 Co radionuclides have been simultaneously produced using the 64 Ni (p, n) 64 Cu nuclear reaction on a low energy proton-only cyclotron [25].
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