In vivo detection of c-MET expression in a rat hepatocarcinogenesis model using molecularly targeted magnetic resonance imaging.
The multifunctional growth factor scatter factor/hepatocyte growth factor and its tyrosine kinase receptor, c-MET, have been implicated in the genesis and malignant progression of numerous human malignancies, including hepatocellular carcinomas. The incidence of hepatocellular carcinomas in the United States has increased noticeably over the past two decades and is listed as the fifth major cancer in men worldwide. In this study, we used a choline-deficient l-amino acid (CDAA)-defined rat hepatocarcinogenesis model to visualize increased in vivo expression of the c-MET antigen in neoplastic lesion formation with the use of a super paramagnetic iron oxide (SPIO)-anti-c-MET molecularly targeted magnetic resonance imaging (MRI) contrast agent. SPIO-anti-c-MET was used for the first time to detect overexpression of c-MET in neoplastic nodules and tumors within the livers of CDAA-treated rats, as determined by a decrease in MRI signal intensity and a decrease in regional T(2) values. Specificity for the binding of the molecularly targeted anti-c-MET contrast agent was determined using rat hepatoma (H4-II-E-C3) cell cultures and immunofluorescence microscopic imaging of the targeting agents within neoplastic liver tissue 1 to 2 hours following intravenous administration of SPIO-anti-c-MET and MRI investigation. This method has the ability to visualize in vivo the overexpression of c-MET at early developmental stages of tumor formation.
Towner
Rheal A
RA
Small Animal MRI Core Facility, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Rheal-Towner@omrf.ouhsc.edu
Smith
Nataliya
N
Tesiram
Yasvir A
YA
Abbott
Andrew
A
Saunders
Debbie
D
Blindauer
Rebecca
R
Herlea
Oana
O
Silasi-Mansat
Robert
R
Lupu
Florea
F
D000818:Animals; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002796:Choline Deficiency / Q000150:complications; D004195:Disease Models, Animal; D042241:Early Diagnosis; D007501:Iron; D008113:Liver Neoplasms / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010087:Oxides; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D019809:Streptavidin
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D010087:Oxides; D011518:Proto-Oncogene Proteins; D019809:Streptavidin; D007501:Iron; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases