In vivo detection of c-Met expression in a rat C6 glioma model.
The tyrosine kinase receptor, c-Met, and its substrate, the hepatocyte growth factor (HGF), are implicated in the malignant progression of glioblastomas. In vivo detection of c-Met expression may be helpful in the diagnosis of malignant tumours. The C6 rat glioma model is a widely used intracranial brain tumour model used to study gliomas experimentally. We used a magnetic resonance imaging (MRI) molecular targeting agent to specifically tag the cell surface receptor, c-Met, with an anti-c-Met antibody (Ab) linked to biotinylated Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-albumin in rat gliomas to detect overexpression of this antigen in vivo. The anti-c-Met probe (anti-c-Met-Gd-DTPA-albumin) was administered intravenously, and as determined by an increase in MRI signal intensity and a corresponding decrease in regional T(1) relaxation values, this probe was found to detect increased expression of c-Met protein levels in C6 gliomas. In addition, specificity for the binding of the anti-c-Met contrast agent was determined by using fluorescence microscopic imaging of the biotinylated portion of the targeting agent within neoplastic and 'normal'brain tissues following in vivo administration of the anti-c-Met probe. Controls with no Ab or with a normal rat IgG attached to the contrast agent component indicated no non-specific binding to glioma tissue. This is the first successful visualization of in vivo overexpression of c-Met in gliomas.
Towner
R A
RA
Small Animal MRI Core Facility, Oklahoma City, OK, USA. Rheal-Towner@omrf.org
Smith
N
N
Doblas
S
S
Tesiram
Y
Y
Garteiser
P
P
Saunders
D
D
Cranford
R
R
Silasi-Mansat
R
R
Herlea
O
O
Ivanciu
L
L
Wu
D
D
Lupu
F
F
D000418:Albumins; D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D003287:Contrast Media; D004195:Disease Models, Animal; D019786:Gadolinium DTPA; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D019809:Streptavidin / Q000378:metabolism
D000418:Albumins; D000911:Antibodies, Monoclonal; D003287:Contrast Media; C058946:albumin-(gadolinium-DTPA); D019809:Streptavidin; D019859:Proto-Oncogene Proteins c-met; D019786:Gadolinium DTPA