Enhancement of hepatic gallium-67 uptake by asialo-transferrin

A significant fraction of intravenously injected 67Ga localizes in the liver. The mechanism of 67Ga uptake by the liver is not clear. Hepatocyte membranes contain galactose-specific receptors which selectively remove asialo-glycoproteins from the circulation by way of endocytosis. In this investigation, we examined whether endocytic uptake of asialo-transferrin would involve 67Ga transport into hepatocytes. We demonstrated that asialo-transferrin bound 67Ga as effectively as apotransferrin. Human asialo-transferrin markedly enhanced 67Ga uptake by isolated, perfused rat livers. Human asialo-orosomucoid, but not orosomucoid competitively inhibited hepatic uptake of the 67Ga asialo-transferrin complex, indicating that hepatic 67Ga uptake in the presence of asialo-transferrin occurred by way of galactose-specific receptors. Our results point to a novel pathway for metal ion transport into hepatocytes by way of galactose receptor mediated endocytosis.