Relevance of anti-.ALPHA.-fetoprotein antibody for radioimmunodetection: Analysis with .ALPHA.-fetoprotein-secreting rat hepatoma and antigen-bound acrylic beads.

Abstract

Using AFP-secreting AH66 rat hepatoma cells and AFP-bound acrylic beads (AFP-B), artificial cells expressing surface antigen, the effect of blood AFP level on the accumulation of radiolabeled rabbit anti-AFP antibody in the site of tumor and beads implanted in rats was examined. Scintigrams of hepatoma-bearing rats with implanted AFP-B showed a marked localization in AFP-B site, but not in the tumor site on day 5 after the injection of radiolabeled antibody. The imaging of AFP-B was most satisfactory in normal rats with extremely low blood AFP. Tissue/blood radioactivity ratio in AFP-B on day 5 was found to be significantly higher in normal rats (17.43±5.55), compared with 6.66+ 1.67 in the tumor-bearing rats (p <0.01), while the ratio of AFP-B in tumor-bearing rats remarkably recovered to 11.20+0.25 (p <0.01) after whole blood exchange to reduce an elevated serum AFP level. The accumulation of anti-AFP antibody in the tumor was not observed irrespective of AFP-B. Microautoradiography of tissue sections showed the specific localization of radioactivity on the surface of AFP-B but not on the surface or the inside of the tumor cells. Immune complexes were detected in plasma of tumor-bearing rats 1 min to 7 days after the administration of the radiolabeled antibody. In conclusion, the application of anti-AFP antibody for the diagnosis and treatment of tumors is limited to the case of the expression of AFP on the surface of tumor cells and lower AFP level in circulation.radioimmunodetection ; AFP ; anti-AFP antibody ; whole blood exchange

The use of a monoclonal antibody against α-fetoprotein for the radioimmunodetection of hepatocellular carcinoma

“…Because AFP is rapidly exported from malignant hepatocytes after synthesis and is not expressed on the cell membrane, it is unlikely that AFP antibody would localize to these cells to an appreciable extent, an observation confirmed by Tanno et al (5). In the study of Koji and his colleagues (2), 30 to 60% of total AFP antibody radioactivity in a tumor homogenate was present in the fraction which contained nuclei and cell membranes (2), which would not have been expected with an export protein.…”

“…Unlike carcinoembryonic antigen, which is expressed on the cell membrane and has been successfully imaged in tumor tissue, AFP is actively secreted by malignant hepatocytes and is found in the cytosol of these cells. Using an experimental model, Tanno et al (5) have recently shown poor localization of AFP antibody to malignant hepatocytes containing cytosolic AFP, but good localization to beads which had been coated with AFP and then embedded in rat tissues. Furthermore, the extremely high serum AFP concentrations which may be encountered in patients with HCC (greater than lo6 ng per ml in some instances) may, because of extensive immune complex formation in the plasma, prevent the AFP antibody from reaching the tumor.…”