Improved production and processing of Zr-89 using a solution target

Objective: The objectives of the present work were to improve the cyclotron production yield of Zr-89 using a solution target, develop a practical synthesis of the hydroxamate resin used to process the target, and develop a biocompatible medium for Zr-89 elution from the hydroxamate resin. Methods: A new solution target (BMLT-2) with enhanced heat dissipation capabilities was designed by using helium-cooled dual foils (0.2 mm Al and 25 mu Havar) and an enhanced water-cooled, elongated solution cavity in the target insert. Irradiations were performed with 14 MeV protons on a 2 M solution of yttrium nitrate in 125 M nitric acid at 40-mu A beam current for 2 h in a closed system. Zirconium-89 was separated from Y by use of a hydroxamate resin. A one-pot synthesis of hydroxamate resin was accomplished by activating the carboxylate groups on a carboxymethyl cation exchange resin using methyl chloroformate followed by reaction with hydroxylamine hydrochloride. After trapping of 89Zr on hydroxamate resin and rinsing the resin with HCl and water to release Y, Zr-89 was eluted with 12 M K2HPO4/KH2PO4 buffer (pH 3.5). ICP-MS was used to measure metal contaminants in the final Zr-89 solution. Results: The BMLT-2 target produced 349 +/- 49 MBq (9.4 +/- 12 mCi) of Zr-89 at the end of irradiation with a specific activity of 1.18 +/- 0.79 GBq/mu g. The hydroxamate resin prepared using the new synthesis method showed a trapping efficiency of 93% with a 75 mg resin bed and 96-97% with a 100-120 mg resin bed. The elution efficiency of Zr-89 with 1.2 M K2HPO4/KH2PO4 solution was found to be 91.7 +/- 3.7%, compared to >95% for 1 M oxalic acid. Elution with phosphate buffer gave very small levels of metal contaminants: Al = 0.40-0.86 mu g (n = 2), Fe = 1.22 +/- 0.71 mu g (n = 3), Y = 0.29 mu g (n = 1). Conclusions: The BMLT-2 target allowed doubling of the beam current for production of 89Zr, resulting in a greater than 2-fold increase in production yield in comparison with a conventional liquid target. The new one-pot synthesis of hydroxamate resin provides a simpler synthesis method for the Zr-89 trapping resin. Finally, phosphate buffer elutes the (89)Zrfrom the hydroxamate resin in high efficiency while at the same time providing a more biocompatible medium for subsequent use of Zr-89. (C) 2015 Elsevier Inc. All rights reserved.