Development of a nano-zirconia based 68Ge/68Ga generator for biomedical applications

Introduction: Most of the commercially available Ge-68/Ga-68 generator systems are not optimally designed for direct applications in a clinical context. We have developed a nano-zirconia based Ge-68/Ga-68 generator system for accessing Ga-68 amenable for the preparation of radiopharmaceuticals. Methods: Nano-zirconia was synthesized by the in situ reaction of zirconyl chloride with ammonium hydroxide in alkaline medium. The physical characteristics of the material were studied by various analytical techniques. A 740 MBq (20 mCi) Ge-68/Ga-68 generator was developed using this sorbent and its performance was evaluated for a period of 1 year. The suitability of Ga-68 for labeling biomolecules was ascertained by labeling DOTA-TATE with Ga-68. Results: The material synthesized was nanocrystalline with average particle size of similar to 7 nm, pore-size of similar to 4 angstrom and a high surface area of 340+/-10 m(2) g(-1). Ga-68 could be regularly eluted from this generator in 0.01N HCl medium with an overall radiochemical yield >80% and with high radionuclidic (<10(-5)% of Ge-68 impurity) and chemical purity (<0.1 ppm of Zr, Fe and Mn ions). The compatibility of the product for preparation of Ga-68-labeled DOTA-TATE under the optimized reaction conditions was found to be satisfactory in terms of high labeling yields (>99%). The generator gave a consistent performance with respect to the elution yield and purity of Ga-68 over a period of 1 year. Conclusions: The feasibility of preparing an efficient Ge-68/Ga-68 generator which can directly be used for biomedical applications has been demonstrated. (C) 2011 Elsevier Inc. All rights reserved.