Gallium-67 uptake by hepatoma: studies in cell cultures, perfused livers, and intact rats

In this investigation, the effect of transferrin on 67Ga uptake by rat hepatoma was studied at three levels: at the level of individual tumor cells in culture; at the level of isolated, perfused livers with implanted intrahepatic tumors; and in intact animals bearing intrahepatic tumors. This approach was possible using H-4-II-E hepatoma cells which grew into discrete tumors when implanted intrahepatically. Transferrin at low concentrations (0.05-0.5 mg/ml) stimulated, while at a higher concentration (1.0 mg/ml) it inhibited 67Ga uptake by tumor cells in culture. In contrast, in isolated, perfused livers with intrahepatic tumors, transferrin at concentration levels of 0.05 and 0.1 mg/ml had no effect, while at 0.25-1.0 mg/ml transferrin inhibited 67Ga uptake by intact tumors. Administration of transferrin which markedly enhanced the serum unsaturated iron binding capacity, had no effect on 67Ga accumulation in the intrahepatic tumors in vivo. These results indicate that, although transferrin at low concentration promotes the uptake of 67Ga by individual tumor cells in culture, it does not do so in intact tumors in isolated rat liver preparations or in tumor bearing rats. We conclude that the mechanism of 67Ga uptake by intact tumors is different from that of tumor cells growing in culture.