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Prevention of Hepatic Metastases by Intravenous Radioactive Gold¹

Division of Surgical Oncology [A. E. A., A. H., B. G., S. S., J. P.] and Nuclear Medicine [N. A. S., J. M., J. S.], State University of New York, Downstate Medical Center, Brooklyn, New York 11203

This investigation was designed to determine whether liver tumor growth can be prevented by localized radioactivity through radioactive gold (¹⁹⁸Au) infusion. Colloidal ¹⁹⁸Au is phagocytosed by Kupffer cells and emits ß- and -radiation. Measurement of -radiation showed marked ¹⁹⁸Au liver concentration. Liver chemistries, histology, and isolated hepatocyte function studies that measure [¹⁴C]acetate incorporation into bile acid and cholesterol formation after doses from 200 to 3000 µCi were serially determined. A 400-µCi dose (2944 rads) provided substantial local radiation in the liver for 9 days without toxicity. Three hundred twenty-seven male 150-g Sprague-Dawley rats received either stable ("cold") colloidal gold, ¹⁹⁸Au, intraportally or through a peripheral vein within 10 min following intraportal infusion of 10,000,000 Walker 256 sarcoma cells. In 66 other rats intraportal ¹⁹⁸Au administration was delayed for 2 weeks after tumor implantation. In rat livers that received ¹⁹⁸Au early following tumor injection, significantly fewer tumors were observed than in controls (p < 10^-9). When radiation was delayed for 2 weeks after tumor infusion, the differences were not as significant.

Intraportal or systemic ¹⁹⁸Au given within 10 min following tumor infusion can protect an animal from hepatic tumor growth without significant liver toxicity. That hepatic radiation may prevent tumor growth may have important clinical implications.

¹ Supported in part by Alan Foss Memorial Fund Grant 1779.

² To whom requests for reprints should be addressed at Box 40, 450 Clarkson Avenue, Brooklyn, N. Y. 11203.

³ John and Mary Markle Scholar in Academic Medicine.

Received 1/27/78. Accepted 5/17/78.