Radioimmunoscintigraphy of tumors autocrine for human met and hepatocyte growth factor/scatter factor

Mol Imaging. Jan-Mar 2002;1(1):56-62. doi: 10.1162/153535002753395716.

Abstract

Inappropriate expression of the c-met-protooncogene product (Met) and/or of its ligand, hepatocyte growth factor/scatter factor (HGF/SF), has been correlated with poor prognosis in a variety of human solid tumors. We are developing animal models for nuclear imaging of Met and HGF/SF expression in tumors in vivo. We radioiodinated a mixture of monoclonal antibodies (MAbs) that bind to human HGF/SF and to the external ligand-binding domain of human Met, and then injected the I-125-MAb mixture intravenously into mice bearing tumors either autocrine for human HGF/SF and human Met or autocrine-paracrine for murine HGF/SF and murine Met. Serial total body gamma camera images were obtained, and regional activity was determined by quantitative region-of-interest (ROI) analysis. Tumors autocrine for human HGF/SF and Met demonstrated significantly more rapid uptake and more rapid clearance of the I-125-MAb mixture than tumors expressing one or both murine homologues, reaching a mean tumor to total body activity ratio of > 0.3 by 1 day postinjection. We conclude that radioimmunodetection of tumors autocrine for human HGF/SF and Met is feasible with an I-125-MAb mixture reactive against the ligand-receptor pair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Binding Sites
  • Hepatocyte Growth Factor / analysis*
  • Humans
  • Iodine Radioisotopes
  • Mice
  • Mice, Transgenic
  • Neoplasms / diagnostic imaging*
  • Proto-Oncogene Proteins c-met / analysis*
  • Radioimmunodetection / methods*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Iodine Radioisotopes
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met