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.
Highlights
Many different radiopharmaceuticals are available for imaging neoplasms
We present our early results of imaging tumors autocrine for human HGF/hepatocyte growth factor / scatter factor (SF) and met-protooncogene product (Met) with a radiolabeled mixture of monoclonal antibody (MAb) reactive against the ligand – receptor pair
S-114 cells fixed in acetone/methanol were stained with both MAb 2F6
Summary
Many different radiopharmaceuticals are available for imaging neoplasms. They range from classical agents such as [I131]sodium iodide, [Tl-201]thallous chloride, and [Ga-67]gallium citrate to highly selective positron-emitting reporter gene detection systems [1,2]. A protein tyrosine kinase receptor, is a transmembrane protein expressed in a wide variety of tissues, but mostly on the surface of epithelial cells. The binding of ligand by Met effects important events in cellular development, including induction of cell proliferation, differentiation, invasion, and motility [3,4]. The aberrant expression of Met and HGF/SF leads to the emergence of an invasive/metastatic phenotype. This conclusion is supported both by transfection experiments and by retrospective analysis of many types of human solid tumors, including cancers of the breast, prostate, brain, colon, bone and soft tissues, kidney, pancreas, liver, and thyroid [3,4]
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