PMID- 16790083 OWN - NLM STAT- MEDLINE DCOM- 20060831 LR - 20240413 IS - 1476-5586 (Electronic) IS - 1522-8002 (Print) IS - 1476-5586 (Linking) VI - 8 IP - 5 DP - 2006 May TI - HGF/SF increases tumor blood volume: a novel tool for the in vivo functional molecular imaging of Met. PG - 344-52 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. FAU - Tsarfaty, Galia AU - Tsarfaty G AD - Van Andel Research Institute, Grand Rapids, MI 49503, USA. FAU - Stein, Gideon Y AU - Stein GY FAU - Moshitch-Moshkovitz, Sharon AU - Moshitch-Moshkovitz S FAU - Kaufman, Dafna W AU - Kaufman DW FAU - Cao, Brain AU - Cao B FAU - Resau, James H AU - Resau JH FAU - Vande Woude, George F AU - Vande Woude GF FAU - Tsarfaty, Ilan AU - Tsarfaty I LA - eng GR - P50 CA093990/CA/NCI NIH HHS/United States GR - P50CA93990/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (Contrast Media) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Cell Line, Tumor MH - Contrast Media/pharmacology MH - Diagnostic Imaging/*methods MH - Female MH - Hepatocyte Growth Factor/*metabolism MH - Humans MH - Mice MH - Mice, Nude MH - Neoplasm Transplantation MH - Neoplasms/blood supply/*pathology MH - *Neovascularization, Pathologic MH - Oxygen/metabolism MH - Oxygen Consumption MH - Prognosis MH - Proto-Oncogene Proteins c-met/*metabolism PMC - PMC1592450 EDAT- 2006/06/23 09:00 MHDA- 2006/09/01 09:00 PMCR- 2006/05/01 CRDT- 2006/06/23 09:00 PHST- 2006/06/23 09:00 [pubmed] PHST- 2006/09/01 09:00 [medline] PHST- 2006/06/23 09:00 [entrez] PHST- 2006/05/01 00:00 [pmc-release] AID - 05685 [pii] AID - 10.1593/neo.05685 [doi] PST - ppublish SO - Neoplasia. 2006 May;8(5):344-52. doi: 10.1593/neo.05685.