The production of high specific activity Cu-64 as measured by ion chromatography

Objectives Carrier-free Cu-64 is produced at Washington University via the (p, n) reaction on enriched Ni-64 and is used in several ongoing clinical trials. We describe new techniques for monitoring and improving specific activity using ion chromatography (IC). We also confirm the direct detection of radioactive copper with IC.

Methods We developed a methodology for detecting and quantifying common impurities in Cu-64. We monitored several productions of Cu-64 and examined the steps in which impurities were introduced into the Cu-64 and how these impurities affected overall specific activity. We have also monitored the decay of Cu-64 into Zn-64 and Ni-64. 25 mCi samples of 64CuCl2 in 0.1 M HCl were diluted to 100 microliters with additional 0.1 M HCl. Samples were injected onto a Dionex IonPac CS5A column at 1.2 ml/min. Post column reagent 4-(2-pyridylazo)resorcinol (PAR) 0.25 mM was used to bind to metal ions and allow the measurement of the absorbance of the metal-PAR complex at 530 nm.

Results We were able to detect Cu-64 using an IC system set up for transition metals detection and monitor the decay of Cu-64 into Ni-64 and Zn-64. We were able to show that impurities in solvents used for Cu-64 production can be detected with IC, and we have monitored where impurities are introduced in an automated production system developed on site. We have also determined the specific metal impurities that affect specific activity.

Conclusions Using this technique, we examined steps of our separation process to determine where impurities are being introduced and what further steps can be taken to purify the Cu-64, allowing us to achieve the production of higher specific activity Cu-64. Going forward, we are comparing the effective specific activity determined by IC to that determined by TETA titrations.

Research Support This work was supported by NIH/NCI Grant R24 CA086307 “Radionuclide Resource for Cancer Applications.\#8221;