TY - JOUR
T1 - HGF/SF increases tumor blood volume
T2 - A novel tool for the in vivo functional molecular imaging of Met
AU - Tsarfaty, Galia
AU - Stein, Gideon Y.
AU - Moshitch-Moshkovitz, Sharon
AU - Kaufman, Dafna W.
AU - Cao, Brain
AU - Resau, James H.
AU - Vande Woude, George F.
AU - Tsarfaty, Ilan
N1 - Funding Information:
Address all correspondence to: Dr. Ilan Tsarfaty, Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. E-mail: [email protected] 1This work was supported, in part, by research grants from the National Institutes of Health (P50CA93990), the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (MAMC 085P1000815), and the Breast Cancer Research Foundation.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - Contrast medium ultrasound
KW - Functional molecular imaging
KW - Hepatocyte growth factor/scatter factor
KW - Met
KW - Receptor tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=33744819163&partnerID=8YFLogxK
U2 - 10.1593/neo.05685
DO - 10.1593/neo.05685
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AN - SCOPUS:33744819163
SN - 1522-8002
VL - 8
SP - 344
EP - 352
JO - Neoplasia
JF - Neoplasia
IS - 5
ER -
