Radioimmunoscintigraphy of tumors autocrine for human met and hepatocyte growth factor/scatter factor.
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.
Hay
Rick V
RV
Van Andel Research Institute, 333 Bostwick N.E., Grand Rapids, MI 49503, USA.
Cao
Brian
B
Skinner
R Scot
RS
Wang
Ling-Mei
LM
Su
Yanli
Y
Resau
James H
JH
Vande Woude
George F
GF
Gross
Milton D
MD
D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D017228:Hepatocyte Growth Factor / Q000032:analysis*; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000000981:diagnostic imaging*; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis*; D016719:Radioimmunodetection / Q000379:methods*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met