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

Int J Cancer. 1999 Feb 9;80(4):559-63. doi: 10.1002/(sici)1097-0215(19990209)80:4<559::aid-ijc13>3.0.co;2-y.

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).

MeSH terms

  • Animals
  • Antibodies, Monoclonal / isolation & purification
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / metabolism
  • Female
  • Fluorescent Antibody Technique, Indirect
  • GPI-Linked Proteins
  • Humans
  • Immunoglobulin G / isolation & purification
  • Immunoglobulin G / metabolism*
  • Indium Radioisotopes / pharmacokinetics
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy
  • Tissue Distribution
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • Immunoglobulin G
  • Indium Radioisotopes
  • Membrane Glycoproteins
  • mesothelin