Ethanol-Based Post-processing of Generator-Derived 68Ga Toward Kit-Type Preparation of 68Ga-Radiopharmaceuticals

Post-processing by means of a cation-exchanger based protocol is an efficient strategy for purification and concentration of generator-derived Ga-68. It ensures the removal of Ge-68 before Ga-68-radiopharmaceutical preparation and high labeling yields of Ga-68-labeled radiopharmaceuticals for routine medical application. Methods: In an effort to overcome the problem associated with acetone in the currently applied method, we have investigated the feasibility of replacing it with ethanol. The purification of Ga-68 from coeluted metallic impurities (Ge-68(4+), Fe3+, Zn2+, and Ti4+) on various cation-exchange columns has been investigated with a variety of post-processing solutions. As a proof of principle, the post-processed Ga-68 was used to radiolabel DOTATOC in combination with high-purity water and various buffer solutions. Results: An effective protocol for the processing of generator-produced Ga-68 on the basis of cation-exchange chromatography using EtOH/HCl medium has been developed. Up to 95% of the initially eluted 68Ga activity can be collected in a 1-mL fraction of 90% EtOH/0.9N HCl after removal of Ge-68-breakthrough in a washing step. The post-processed eluate has been used to radiolabel DOTATOC in yields of approximately 97% 0.25% at 80 degrees C in 5 min. Conclusion: The described novel protocol improves the radiolabeling efficiency and efficacy of DOTATOC, providing yields of greater than 99% (decay-corrected). As a result, further purification to separate the desired product from uncomplexed Ga-68 is not necessary. The developed post-processing and labeling protocols permit reliable and high-yield preparation of injectable Ga-68-DOTATOC (or other Ga-68-labeled radiopharmaceuticals) that are suitable for routine application. It is possible to incorporate this protocol into existing automated modules.