The importance of pH and citrate concentration on the in vitro and in vivo behavior of Radiogallium

Abstract

The influence of pH and citrate concentration on radio labeled gallium citrate has been investigated in vitro and in vivo as an aid to understanding the behavior of this radiopharmaceutical. Using paper chromatography, we have shown that a competition for gallium exists between hydroxyl and citrate ions in solution such that effective chelation occurs only at low pH or high citrate concentration. The influence of preparation pH has been investigated in tumour-bearing rats; the biodistribution of 67Ga was found to be virtually unaffected by pH in the range of 6–10. The influence of citrate on dog serum-protein binding has been studied using gel filtration and equilibrium dialysis; our results show that a competition for gallium exists in serum environments between serum proteins and citrate such that an increase in citrate concentration will result in dissocation of gallium bound to protein. The results of this study indicate that gallium citrate is unstable in vivo and that gallium exists in serum environments largely bound to serum proteins.