Technical noteA semi-automated system for the routine production of copper-64
Highlights
► 64Cu is an isotope of interest for Positron Emission Tomography (PET) and radiotherapy. ► A semi-automated system for the production of 64Cu is reported. ► This system has the capability to produce large amounts of this isotope reliably on a weekly basis. ► This includes dissolution of the nickel target material and separation using ion chromatography.
Introduction
Copper-64 is of interest as a isotope for positron emission tomography (PET). It has a relatively long half-life (compared to oxygen-15, nitrogen-13, and fluoring-18, commonly used in PET) of 12.74 h, and a relatively low positron energy (β max=0.655 MeV) which are both desirable imaging characteristics for imaging timepoints of up to 48 hours. These characteristics make Cu-64 a suitable radioisotope for molecular imaging of small molecules as well as peptides and antibodies (Anderson and Welch, 1999, Smith, 2004, Anderson et al., 2007, Wadas et al., 2007, Anderson and Ferdani, 2009, Shokeen and Anderson, 2009). This isotope is also currently being used in a multi center trial for hypoxia imaging with the radiopharmaceutical [64Cu]ATSM (Dehdashti, 2008). Other clinical trials involving radiolabeled antibodies are also in progress (Carrasquillo, 2010).
No-carrier added Cu-64 has been produced on a particle accelerator via the (p,n) reaction (Szelecsenyi et al., 1993) at many centers. Washington University has been producing Cu-64 since 1995 on a biomedical cyclotron using this reaction (McCarthy et al., 1997). The 12.7 h half-life allows the radioisotope to be shipped to other research sites within the United States, providing researchers the ability to work with the radioisotope without having direct access to a cyclotron. The amount of activity shipped from our institution to other centers has increased from less than 2 Ci in 2000 to nearly 10 Ci in 2010, reflecting an increased interest in using Cu-64 for both basic research and clinical studies. This increased demand for Cu-64 has necessitated the routine automated production of this isotope. In 2010, our group conducted 48 production runs, totaling over 22 Ci of produced activity. Automation is now an integral part of our reliable production of large amounts of Cu-64. Our automation system allows us to effectively purify the Cu-64 from the target with high amounts (∼500 mCi) of starting radioactivity while minimizing dose to the operator.
Section snippets
Reagents and Materials
Analytical grade materials (Concentrated HCl 99.999999% pure (metals basis), concentrated HNO3 99.9999% pure (metals basis), Alfa Aesar, and 18 mOhm (MilliQ) water) were used throughout the process.
Electroplating
The target for Cu-64 production is a gold disk (19 mm diameter x 1.5 mm thickness) that is electroplated with highly enriched nickel-64 (Isoflex USA, San Francisco, CA) as reported previously (McCarthy et al., 1997). Typical enrichment levels of batches of the initial Ni-64 are summarized in Table 1.
Results and discussion
Since introducing the first iteration of the automated module in October 2008, 145 productions have been completed, producing over 53 Ci of 64Cu. Using TETA titrations we've measured the ESA to be on average 14,000±7600 mCi/μmol or approximately 10–20 atoms of carrier metal per one atom of 64Cu. When analyzed 4 h after end of irradiation, 61Co (T1/2=1.65 h) is observed as 2.84±1.70% of Cu-64 activity and is the only significant contaminant. As the half-life of this isotope is considerable shorter
Conclusions
We have succeeded in developing a module that is capable of handling weekly productions of 64Cu and recover the radioactivity from the target at high yields. Automating the separation process has enabled Washington University to scale up our production in order to meet the increased demand from both on-site and off-site researchers for this relevant medical radioisotope, while providing increased shielding for the operator. We are continuing to investigate ways of reducing the introduction of
Acknowledgments
The authors would like to acknowledge Patricia Margenau, and David Ficke for operation of the CS15 cyclotron and Paul Eisenbeis for target preparation. This work was supported in part by NIH/NCI grant R24 CA086307, “Radionuclide Resource for Cancer Applications.”
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