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Gallium-67 Uptake by Hepatoma: Studies in Cell Cultures, Perfused Livers, and Intact Rats

Divisions of Nuclear Medicine and Radiation Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland
Research Service, Veterans Administration Medical Center, Albany, New York

Correspondence: For reprints contact: Ursula Scheffel, ScD, Div. of Nuclear Medicine, Traylor 301, 720 Rutland Ave., Baltimore, MD 21205.

ABSTRACT

In this investigation, the effect of transferrin on ⁶⁷Ga uptake by rat hepatoma was studied at three levels: (a) at the level of individual tumor cells in culture; (b) at the level of isolated, perfused livers with implanted intrahepatic tumors; and (c) 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) ft 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.