Preparation and Preliminary Evaluation of 63Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc

Abnormalities of zinc homeostasis are indicated in many human diseases. A noninvasive imaging method for monitoring zinc in the body would be useful to understand zinc dynamics in health and disease. To provide a PET imaging agent for zinc, we have investigated production of Zn-63 (half-life, 38.5 min) via the Cu-63(p,n)Zn-63 reaction using isotopically enriched solutions of Cu-63-copper nitrate. A solution target was used for rapid isolation of the Zn-63 radioisotope from the parent Cu-63 ions. Initial biologic evaluation was performed by biodistribution and PET imaging in normal mice. Methods: To produce Zn-63, solutions of Cu-63-copper nitrate in dilute nitric acid were irradiated by 14-MeV protons in a low-energy cyclotron. An automated module was used to purify Zn-63 from Cu-63 in the target solution. The Cu-63-Zn-63 mixture was trapped on a cation-exchange resin and rinsed with water, and the Zn-63 was eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized with NaHCO3, and the Zn-63 was then trapped on a carboxymethyl cartridge, washed with water, and eluted with isotonic 4% sodium citrate. Standard quality control tests were performed on the product according to current good manufacturing practice, including radionuclidic identity and purity, and measurement of nonradioactive Zn+2, Cu+2, Fe+3, and Ni+2 by ion-chromatography high-performance liquid chromatography. Biodistribution and PET imaging studies Were performed in B6.SJL mice after intravenous administration of Zn-63-zinc citrate. Cu-63 target material was recycled by eluting the initial resin with 4N HNO3. Results: Yields of 1.07 +/- 0.22 GBq (uncorrected at 30-36 min after end of bombardment) of Zn-63-zinc citrate were obtained with a 1.23 M Cu-63-copper nitrate solution. Radionuclidic purity was greater than 99.9%, with copper content lower than 3 mu g/batch. Specific activities were 41.2 +/- 18.1 MBq/mu g (uncorrected) for the Zn-63 product. PET and biodistribution studies in mice at 60 min showed expected high uptake in the pancreas (standard uptake value, 8.8 +/- 3.2), liver (6.0 +/- 1.9), upper intestine (4.7 +/- 2.1), and kidney (4.2 +/- 1.3). Conclusion: A practical and current good manufacturing practice-compliant preparation of radionuclidically pure Zn-63-zinc citrate has been developed that will enable PET imaging studies in animal and human studies. 63Zn-zinc citrate showed the expected biodistribution in mice.