title: HGF/SF increases tumor blood volume: a novel tool for the in vivo functional molecular imaging of Met.
abstract: Molecular functional and metabolic imaging allows visualization of disease-causing processes in living organisms. Here we present a new approach for the functional molecular imaging (FMI) of endogenous tyrosine kinase receptor activity using Met and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), as a model. HGF/SF and Met play significant roles in the biology and pathogenesis of a wide variety of cancers and, therefore, may serve as potential targets for cancer prognosis and therapy. We have previously shown that Met activation by HGF/SF increases oxygen consumption in vitro and results in substantial alteration of blood oxygenation levels in vivo, as measured by blood oxygenation level-dependent magnetic resonance imaging. Using contrast medium (CM) ultrasound imaging, we demonstrate here that HGF/SF induces an increase in tumor blood volume. This increase is evident in small vessels, including vessels that were not detected before HGF/SF treatment. The specificity of the effect was validated by its inhibition using anti-HGF/SF antibodies. This change in tumor hemodynamics, induced by HGF/SF and measured by CM ultrasound, is further used as a tool for Met FMI in tumors. This novel noninvasive molecular imaging technique may be applied for the in vivo diagnosis, prognosis, and therapy of Met-expressing tumors.
authors.affiliation: Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Galia
authors.initials: G
authors.lastname: Tsarfaty
authors.forename: Gideon Y
authors.initials: GY
authors.lastname: Stein
authors.forename: Sharon
authors.initials: S
authors.lastname: Moshitch-Moshkovitz
authors.forename: Dafna W
authors.initials: DW
authors.lastname: Kaufman
authors.forename: Brain
authors.initials: B
authors.lastname: Cao
authors.forename: James H
authors.initials: JH
authors.lastname: Resau
authors.forename: George F
authors.initials: GF
authors.lastname: Vande Woude
authors.forename: Ilan
authors.initials: I
authors.lastname: Tsarfaty
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D010100:Oxygen