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Am J Nucl Med Mol Imaging 2013;3(4):300-311
Original Article
Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma
models
Ting He, Nataliya Smith, Debra Saunders, Benjamin P Pittman, Megan Lerner, Stanley Lightfoot, Robert Silasi-Mansat, Florea Lupu,
Rheal A Towner
Advanced Magnetic Resonance Center, Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104
USA; Oklahoma Center for Neuroscience, Department of Surgery, Department of Pathology, University of Oklahoma Health Sciences
Center, Okla-homa City, OK 73104 USA
Received April 15, 2013; Accepted June 21, 2013; Epub July 10, 2013; Published July 15, 2013
Abstract: Vascular endothelial growth factor receptor 2 (VEGFR2) is an important angiogenic marker over-expressed in gliomas.
With the use of molecular magnetic resonance imaging (mMRI) differing levels of VEGFR2 can be characterized in vivo with in rodent
gliomas varying in angiogenesis. VEGFR2 levels were assessed by intravenous administration of an anti-VEGFR2 probe (anti-
VEGFR2-albumin-Gd (gadolini-um)-DTPA (diethylene triamine penta acetic acid)-biotin) into C6 or RG2 glioma-bearing rats, and
visualized with mMRI. A non-specific IgG was coupled to the albumin-Gd-DTPA-biotin construct as a contrast agent molecular weight
control. VEGFR2 levels are heterogeneous in different regions of C6 gliomas, whereas VEGFR2 was more homogenous or evenly
distributed in RG2 gliomas. RG2 gliomas have less VEGFR2 within tumor periphery and peri-necrotic (p<0.05) regions, but more
VEGFR2 within tumor interior regions (p<0.01), compared to C6 gliomas. mMRI results were confirmed with fluorescence staining
and mean fluorescence intensity (MFI) quantification of the anti-VEGFR2 probe in excised glioma and brain tissues, as well as
detection of VEGFR2 in C6 and RG2 gliomas and corresponding contalateral brain tissues. Ex vivo VEGFR2 levels were found to be
significantly higher in C6 gliomas compared to RG2 tumors (p<0.001), which corresponded with in vivo detection using the VEGFR2
probe. Immunohistochemistry staining for HIF-1α (hypoxia inducible factor 1α), which is associated with angiogenesis, indicated
higher levels in RG2 (p<0.01) compared to C6 gliomas. The data suggests that C6 gliomas have angiogenesis which is associated
more with large blood vessels in tumor periphery and peri-necrotic regions, and less microvascular angiogenesis within the tumor
interior, compared to RG2 gliomas. (ajnmmi1304001).
Keywords: Molecular magnetic resonance imaging (mMRI), vascular endothelial growth factor receptor 2 (VEGFR2), C6 and RG2 rat
gliomas, in vivo, fluorescence imaging
Address correspondence to: Rheal A Towner, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation,
Oklahoma City, OK 73104 USA. Phone: 1-405-271-7383; E-mail: Rheal-Towner@omrf.org
Original Article
Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma
models
Ting He, Nataliya Smith, Debra Saunders, Benjamin P Pittman, Megan Lerner, Stanley Lightfoot, Robert Silasi-Mansat, Florea Lupu,
Rheal A Towner
Advanced Magnetic Resonance Center, Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104
USA; Oklahoma Center for Neuroscience, Department of Surgery, Department of Pathology, University of Oklahoma Health Sciences
Center, Okla-homa City, OK 73104 USA
Received April 15, 2013; Accepted June 21, 2013; Epub July 10, 2013; Published July 15, 2013
Abstract: Vascular endothelial growth factor receptor 2 (VEGFR2) is an important angiogenic marker over-expressed in gliomas.
With the use of molecular magnetic resonance imaging (mMRI) differing levels of VEGFR2 can be characterized in vivo with in rodent
gliomas varying in angiogenesis. VEGFR2 levels were assessed by intravenous administration of an anti-VEGFR2 probe (anti-
VEGFR2-albumin-Gd (gadolini-um)-DTPA (diethylene triamine penta acetic acid)-biotin) into C6 or RG2 glioma-bearing rats, and
visualized with mMRI. A non-specific IgG was coupled to the albumin-Gd-DTPA-biotin construct as a contrast agent molecular weight
control. VEGFR2 levels are heterogeneous in different regions of C6 gliomas, whereas VEGFR2 was more homogenous or evenly
distributed in RG2 gliomas. RG2 gliomas have less VEGFR2 within tumor periphery and peri-necrotic (p<0.05) regions, but more
VEGFR2 within tumor interior regions (p<0.01), compared to C6 gliomas. mMRI results were confirmed with fluorescence staining
and mean fluorescence intensity (MFI) quantification of the anti-VEGFR2 probe in excised glioma and brain tissues, as well as
detection of VEGFR2 in C6 and RG2 gliomas and corresponding contalateral brain tissues. Ex vivo VEGFR2 levels were found to be
significantly higher in C6 gliomas compared to RG2 tumors (p<0.001), which corresponded with in vivo detection using the VEGFR2
probe. Immunohistochemistry staining for HIF-1α (hypoxia inducible factor 1α), which is associated with angiogenesis, indicated
higher levels in RG2 (p<0.01) compared to C6 gliomas. The data suggests that C6 gliomas have angiogenesis which is associated
more with large blood vessels in tumor periphery and peri-necrotic regions, and less microvascular angiogenesis within the tumor
interior, compared to RG2 gliomas. (ajnmmi1304001).
Keywords: Molecular magnetic resonance imaging (mMRI), vascular endothelial growth factor receptor 2 (VEGFR2), C6 and RG2 rat
gliomas, in vivo, fluorescence imaging
Address correspondence to: Rheal A Towner, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation,
Oklahoma City, OK 73104 USA. Phone: 1-405-271-7383; E-mail: Rheal-Towner@omrf.org
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