Study on Separation and Purification Process of Cyclotron-produced Nuclide ⁶⁸Ge

Germanium-68 (⁶⁸Ge) is a critical precursor for the ⁶⁸Ge/⁶⁸Ga generator, which produces the positron-emitting radionuclide gallium-68 (⁶⁸Ga). The large-scale production of ⁶⁸Ge is of great significance for the clinical application of ⁶⁸Ga-labeled radiopharmaceuticals. A primary production route involves the proton irradiation of solid Ga-Ni alloy target. However, the subsequent target dissolution solution contains not only the desired ⁶⁸Ge but also high concentrations of stable metal impurities (e.g., Ga, Ni, Co, Fe, Cu, Zn) from the target matrix and co-produced radionuclidic impurities (e.g., ⁶⁵Zn, ^56,57,58Co, ⁶⁷Ga), necessitating highly efficient and selective separation processes to meet application requirements. This study developed and validated a novel double-column chromatographic separation method that combines hydroxamate resin and Sephadex G-25 resin for the efficient separation and purification of ⁶⁸Ge from cyclotron-irradiated Ga-Ni alloy target. First, the Ga-Ni alloy target was dissolved using a sulfuric acid-hydrogen peroxide mixture system at 95 ℃. The resulting solution was then processed through the primary hydroxamate resin. Under optimized high-acidity conditions, the resin exhibited exceptional selectivity, strongly adsorbing ⁶⁸Ge while allowing the bulk of co-existing metal impurities (Ga, Ni, Co, Zn, Fe, Cu) to be washed away. The adsorbed ⁶⁸Ge was efficiently recovered by elution with a sodium citrate solution. This intermediate product was subsequently transferred to a secondary Sephadex G-25 column for final purification. Under an alkaline sodium citrate system (pH=12.5), residual cationic impurities were effectively removed, and the purified ⁶⁸Ge was ultimately recovered in a low-concentration hydrochloric acid solution. The entire chemical workflow, from target dissolution through the double-column chromatographic separation to final product collection, was integrated into a self-designed and custom-built automatic separation apparatus, ensuring reproducibility and operational safety. The adsorption characteristics of germanium on hydroxamate resin and Sephadex G-25 resin were systematically investigated, and the washing and desorption conditions were optimized. The optimized process was then validated through the automated separation tests of ⁶⁸Ge from irradiated Ga-Ni alloy target. The results of the double-column separation experiments show that under optimized elution conditions, the majority of impurities, including Ga, Ni, Co, Zn, Fe, and Cu, could be effectively removed during the hydroxamate resin separation step, while the residual trace impurities were further purified during the Sephadex G-25 purification step. The results of the ⁶⁸Ge separation validation tests demonstrate that the process can achieve a ⁶⁸Ge separation recovery rate exceeding 90%, with a radionuclide purity above 99.9%. Crucially, the contents of key elemental impurities in the high-activity product are all below 5.5 μg/GBq. The developed double-column separation process is stable and efficient, making it suitable for the large-scale purification and preparation of ⁶⁸Ge.