The role of ferritin in the intracellular distribution of gallium 67

The binding of gallium 67 or iron 59 to ferritin in vitro was investigated using equilibrium dialysis. Gallium 67 did not bind to apo-ferritin until the protein was transformed into ferritin in the presence of iron citrate. Apotransferrin inhibited the binding of ⁶⁷Ga to ferritin, especially in the presence of sodium bicarbonate and citrate, thus indicating that ⁶⁷Ga has not gained access to ferritin from its complex with transferrin. Similar inhibition was observed for ferritin-⁵⁹Fe. The release of ⁵⁹Fe from its transferrin complex was enhanced by ATP, citrate, or ascorbic acid, while these reagents did not stimulate the dissociation of ⁶⁷Ga from its transferrin complex. On the other hand, ⁶⁷Ga injected intravenously in vivo was not found in the ferritin fractions of rat liver, kidney, and tumor. The difference between experimental results in vivo and in vitro supports the hypothesis that ⁶⁷Ga in the cytoplasm is not labile enough to be bound to ferritin. We have indicated a significant role of ferritin in distinguishing between ⁶⁷Ga and ⁵⁹Fe in the cell, and provided some clues to interpret the chemical forms of ⁶⁷Ga in the cytoplasm.