RT Journal Article SR Electronic T1 Preparation and Preliminary Evaluation of 63Zn-Zinc Citrate as a Novel PET Imaging Biomarker for Zinc JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1348 OP 1354 DO 10.2967/jnumed.114.141218 VO 55 IS 8 A1 Timothy R. DeGrado A1 Mukesh K. Pandey A1 John F. Byrne A1 Hendrik P. Engelbrecht A1 Huailei Jiang A1 Alan B. Packard A1 Kevin A. Thomas A1 Mark S. Jacobson A1 Geoffrey L. Curran A1 Val J. Lowe YR 2014 UL http://jnm.snmjournals.org/content/55/8/1348.abstract AB 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 63Zn (half-life, 38.5 min) via the 63Cu(p,n)63Zn reaction using isotopically enriched solutions of 63Cu-copper nitrate. A solution target was used for rapid isolation of the 63Zn radioisotope from the parent 63Cu ions. Initial biologic evaluation was performed by biodistribution and PET imaging in normal mice. Methods: To produce 63Zn, solutions of 63Cu-copper nitrate in dilute nitric acid were irradiated by 14-MeV protons in a low-energy cyclotron. An automated module was used to purify 63Zn from 63Cu in the target solution. The 63Cu–63Zn mixture was trapped on a cation-exchange resin and rinsed with water, and the 63Zn was eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized with NaHCO3, and the 63Zn 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 63Zn-zinc citrate. 63Cu 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 63Zn-zinc citrate were obtained with a 1.23 M 63Cu-copper nitrate solution. Radionuclidic purity was greater than 99.9%, with copper content lower than 3 μg/batch. Specific activities were 41.2 ± 18.1 MBq/μg (uncorrected) for the 63Zn 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 63Zn-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.