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

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). Int. J. Cancer80:559–563, 1999. Published 1999 Wiley‐Liss, Inc.