Scintigraphy and biodistribution of monoclonal adrenocortical antibody in mice grafted with human adrenocortical carcinoma.

Abstract

A murine monoclonal antibody recognizing normal and neoplastic human adrenocortical cells has been evaluated for scintigraphic localization and biodistribution in 53 nude mice grafted subcutaneously with human adrenocortical cell lines SW-13 and T-CAR 1. The immunoglobulin G1 antibody and its Fab'2 fragment were purified and labeled with 125I. The tumor grafts exhibited diameters of 5 to 15 mm at 4 to 6 weeks after transplantation, when mice received a single subcutaneous or intraperitoneal injection of 50 micrograms iodinated intact or fragmented antibody, respectively. Examination up to 8 days after immunoglobulin G administration showed mean radioactivity ratios less than 1.0 for tumor to blood and corresponding ratios in tumor to lung, liver, spleen, and kidney from 0.6 to 5.3 at the time of peak tumor to blood ratio. A high background activity was noted on scintigraphic tumor visualization with the iodinated immunoglobulin G. In contrast, the radiolabeled Fab'2 fragment displayed gradually rising tumor to blood ratios, which, 4 days after injection, averaged 10.5 for T-CAR1 and 5.3 for SW-13. Tumor transplants were scintigraphically visualized without substantial background activity 3 days after Fab'2 injection, when the ratio of radioactivity in the tumor to the investigated murine organs was 0.5 to 7.3. The findings substantiate that immunoscintigraphy with the Fab'2 fragment of the antiadrenocortical Ac5 antibody may become a tool to localize human adrenocortical carcinoma.