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Localization of Radioiodinated Antibody to -Fetoprotein in Hepatoma Transplanted in Rats and a Case Report of -Fetoprotein Antibody Treatment of a Hepatoma Patient¹

The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan [T. K., N. I., T. M., Y. K., S. N., A. T.], and Department of Biochemistry, Hokkaido University, School of Medicine, Sapporo, Hokkaido, Japan [A. H., K. K., Y. T., S. N., H. H.]

The localization of radioactive iodine-labeled anti--fetoprotein (AFP) antibody in transplanted rat hepatomas was examined by total body scintigraphy, subcellular distribution of radioactivity, and microautoradiography of tissues. The specific antibody was isolated from anti-rat AFP horse antiserum by immunoadsorbent that was coupled with rat AFP and radioiodinated with ¹²⁵I. F(ab')₂ was isolated from peptic digests of the specific antibody. Normal horse IgG was taken as control. Scintigrams taken 48 to 168 hr after injection of the radiolabeled antibody or its F(ab')₂ showed a remarkable localization in the tumors. Normal immunoglobulin G was also taken up in the tumor to some extent.

The tumor/blood radioactivity ratio determined 7 days after the injection was about 4 times higher in the experimental group than was that in the control group, and the ratio on Day 7 was over 1.0. This indicated the active accumulation of the radiolabeled specific antibody in the tumor.

Tumor tissues were homogenized and fractionated into subcellular fractions. About 30 to 60% of the total radioactivity in the homogenate was found in a fraction which contained cell membrane and nucleus.

Microautoradiograms of the tissue sections showed the specific localization of radioactivity in the tumor but not in noncancerous tissues. Normal immunoglobulin G did not show significant localization in the tumor. These experimental results indicated the specific uptake of the radiolabeled antibody to AFP into AFP-producing tumor cells.

A patient with an inoperable hepatoma was given 450 mg of purified anti-human AFP horse antibody i.v. Serum AFP level decreased in 2 days to the normal level (< 10 ng/ml), and this low level has been maintained continuously for over 4 months. To date, the clinical effect of the antibody to tumor has not been exhibited. No side effect of the horse antibody was observed.

¹ Presented at the UICC Workshop on Radioimmunodetection of Cancer, July 19 to 21, 1979, Lexington, Ky.