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

Journal of Nuclear Medicine

Geoffrey L. Curran¹  Val J. Lowe¹  Huailei Jiang¹  Hendrik P. Engelbrecht¹  Mark S. Jacobson¹  Kevin A. Thomas¹  Mukesh K. Pandey¹  Alan B. Packard¹  Timothy R. DeGrado¹  John F. Byrne¹ 

关键词: ⁶³Zn;    PET;    radioisotope production;    solution target;   

DOI  :  10.2967/jnumed.114.141218

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown