Technical note A semi-automated system for the routine production of copper-64 Maiko Kume, Paul C. Carey, Gregory Gaehle, Evelyn Madrid, Thomas Voller, William Margenau, Michael J. Welch, Suzanne E. Lapi n Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO 63110, USA article info Article history: Received 19 July 2011 Received in revised form 28 February 2012 Accepted 5 March 2012 Available online 15 March 2012 Keywords: Copper-64 Isotope production PET Automation abstract An automated system for the production of high specific activity 64 Cu via the irradiation of electroplated enriched 64 Ni targets has been developed. We have been operating this system continually on a biweekly or weekly basis for more than two years. Since the inception of this automated production system, (October 1, 2008), we have had 145 productions, produced 53562 mCi and shipped out 25629 mCi of this isotope to external users. We routinely produce over 400 mCi of this isotope per batch with a specific activity of 14,000 77600 mCi/mmol for distribution to some 12–15 centers each production. & 2012 Elsevier Ltd. All rights reserved. 1. 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 (b max ¼ 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 [ 64 Cu]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 accel- erator 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 produc- tion 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 radio- activity while minimizing dose to the operator. 2. Methods 2.1. Reagents and Materials Analytical grade materials (Concentrated HCl 99.999999% pure (metals basis), concentrated HNO 3 99.9999% pure (metals basis), Alfa Aesar, and 18 mOhm (MilliQ) water) were used throughout the process. 2.2. 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. Targets are typically plated with 60–80 mg of Ni-64. 2.3. Module design A safe, robust, reliable and user friendly system was desired for automated production. A flow chart of the purification process is Contents lists available at SciVerse ScienceDirect journal homepage: www.elsevier.com/locate/apradiso Applied Radiation and Isotopes 0969-8043/$ - see front matter & 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.apradiso.2012.03.009 n Corresponding author. Tel.: þ1 314 362 4696. E-mail address: lapis@mir.wustl.edu (S.E. Lapi). Applied Radiation and Isotopes 70 (2012) 1803–1806