PMID- 11406565
OWN - NLM
STAT- MEDLINE
DCOM- 20010712
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 61
IP  - 12
DP  - 2001 Jun 15
TI  - In vivo molecular imaging of met tyrosine kinase growth factor receptor activity 
      in normal organs and breast tumors.
PG  - 4873-8
AB  - Molecular imaging techniques allow visualization of specific gene products and 
      their physiological processes in living tissues. In this study, we present a new 
      approach for molecular imaging of endogenous tyrosine kinase receptor activity. 
      Met and its ligand hepatocyte growth factor scatter factor (HGF/SF), which 
      mediate mitogenicity, tumorigenicity, and angiogenesis, were used as a model. 
      HGF/SF and Met play a significant role in the pathogenesis and biology of a wide 
      variety of human epithelial cancers and, therefore, may serve as potential 
      targets for cancer prognosis and therapy. We have shown previously that in vitro 
      activation of Met by HGF/SF increases oxygen consumption. In this study, we 
      demonstrate that Met activation in vivo by HGF/SF alters the hemodynamics of 
      normal and malignant Met-expressing tissues. Tumor-bearing BALB/C mice were i.v. 
      injected with HGF/SF and imaged using magnetic resonance imaging (MRI) and 
      Doppler ultrasound. Organs and tumors expressing high levels of Met showed the 
      most substantial alteration in blood oxygenation levels as measured by blood 
      oxygenation level depended (BOLD)-MRI. No significant alteration was observed in 
      tumors or organs that does not express Met. In the liver, which expresses high 
      levels of Met, MRI signal alteration of about 60% was observed. In the kidneys, 
      signal alteration was approximately 30%, and no change was observed in muscles. 
      The extent of MRI signal alteration was also in correlation with HGF/SF doses. 
      Injection of 7 and 170 ng/g body weight resulted in signal alteration of 5% and 
      30%, respectively, in tumors. Doppler ultrasound measurements demonstrated that 
      these MRI changes are at least partially attributable to altered blood flow. 
      These hemodynamic alterations, measured by MRI and Doppler ultrasound, were used 
      in this study for the molecular imaging of Met activity in vivo. This novel 
      molecular imaging technique may be used for in vivo diagnosis, prognosis, and 
      therapy of Met-expressing tumors.
FAU - Shaharabany, M
AU  - Shaharabany M
AD  - fBIT LTD, Rad Ramot Bio-Medical Incubator, Tel-Hashomer 52656.
FAU - Abramovitch, R
AU  - Abramovitch R
FAU - Kushnir, T
AU  - Kushnir T
FAU - Tsarfaty, G
AU  - Tsarfaty G
FAU - Ravid-Megido, M
AU  - Ravid-Megido M
FAU - Horev, J
AU  - Horev J
FAU - Ron, R
AU  - Ron R
FAU - Itzchak, Y
AU  - Itzchak Y
FAU - Tsarfaty, I
AU  - Tsarfaty I
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adenocarcinoma/blood supply/*enzymology
MH  - Animals
MH  - Enzyme Activation
MH  - Female
MH  - Hemodynamics/drug effects
MH  - Hepatocyte Growth Factor/pharmacology
MH  - Magnetic Resonance Imaging
MH  - Mammary Neoplasms, Experimental/blood supply/*enzymology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oxygen/blood
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - Ultrasonography, Doppler, Color
EDAT- 2001/06/19 10:00
MHDA- 2001/07/13 10:01
CRDT- 2001/06/19 10:00
PHST- 2001/06/19 10:00 [pubmed]
PHST- 2001/07/13 10:01 [medline]
PHST- 2001/06/19 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2001 Jun 15;61(12):4873-8.