111Indium-labeled monoclonal antibody K1: biodistribution study in nude mice bearing a human carcinoma xenograft expressing mesothelin

Abstract

The monoclonal antibody (MAb) K1 is a murine IgG1 that recognizes mesothelin, a differentiation antigen present on mesothelium which is highly expressed on cancers derived from mesothelium, including most ovarian cancers and epithelioid mesotheliomas. MAb K1 was conjugated to 2-(p-isothiocyanatobenzyl)-cyclohexyl- diethylenetriaminepentaacetic acid and labeled with 111In. The biodistribution of 111In-K1 was studied in athymic nude mice bearing 2 s.c. tumors, one expressing a stably transfected plasmid encoding mesothelin and one composed of the parental untransfected A431 epidermoid carcinoma cells which do not express mesothelin. Tumor-bearing mice were given an i.v. injection of 111In-K1 and killed at different time points to determine the uptake of radiolabeled antibody. Significantly higher uptake was seen in antigen-positive tumors at all time points, with peak values at 72 hr (52.9% vs. 8% of the injected dose/g tissue for antigen-positive and antigen-negative tumors, respectively). Uptake in antigen-positive tumors was higher than the blood level at all time points, and the tumors contained a high level of the radiolabeled MAb even at 7 days (28.6% of the injected dose/g tumor).