Comparative Evaluation of Buffering Systems for Optimizing the Labeling Efficiency of 68 Ga-labeled Radiopharmaceuticals

pH is a critical factor in 68 Ga-labeled radiopharmaceutical synthesis, significantly influencing the radiochemical yield by determining the chemical states of the radioisotope and chelator.Therefore, establishing a buffering system capable of maintaining an optimal pH for coordinate covalent bonding is essential to ensure high labeling efficiency and process reproducibility.In this study, sodium acetate, ammonium acetate, and HEPES were selected as buffering agents to evaluate the impact of the buffer capacity on the labeling efficiency of [ 68 Ga]Ga-DOTA-TOC.The experimental results showed that sodium acetate and ammonium acetate achieved optimal radiochemical purity and yield at approximately pH 4.0.On the other hand, HEPES maintained high radiochemical purity and yield over a broader capacity range even at lower pH compared to the acetate buffers.In conclusion, although HEPES is superior in terms of process reproducibility, strict compliance with residual toxicity standards is required for human administration.Conversely, acetate-based buffers show excellent biocompatibility but require precise dosage design prior to synthesis because of their sensitivity.These findings are expected to serve as fundamental data for minimizing the trial-and-error that may occur when switching 68 Ge/ 68 Ga generator suppliers or introducing new 68 Ga-labeled radiopharmaceuticals.