Localization of radioiodinated antibody to alpha-fetoprotein in hepatoma transplanted in rats and a case report of alpha-fetoprotein antibody treatment of a hepatoma patient.

The localization of radioactive iodine-labeled anti-a-fetoprotein (AFP) antibody in transplanted rat hepatomas was exam ined by total body scintigraphy, subcellular distribution of ra dioactivity, 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')? 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 spe cific localization of radioactivity in the tumor but not in noncancerous tissues. Normal immunoglobulin G did not show signifi cant localization in the tumor. These experimental results indi cated 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.