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He T, Smith N, Saunders D, et al. Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma models. Am J Nucl Med Mol Imaging. 2013;3(4):300-11
He, T., Smith, N., Saunders, D., Pittman, B. P., Lerner, M., Lightfoot, S., Silasi-Mansat, R., Lupu, F., & Towner, R. A. (2013). Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma models. American journal of nuclear medicine and molecular imaging, 3(4), 300-11.
He, Ting, et al. "Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma models." American journal of nuclear medicine and molecular imaging vol. 3,4 (2013): 300-11.
He T, Smith N, Saunders D, Pittman BP, Lerner M, Lightfoot S, Silasi-Mansat R, Lupu F, Towner RA. Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma models. Am J Nucl Med Mol Imaging. 2013 Jul 10;3(4):300-11. Print 2013. PMID: 23901356; PMCID: PMC3715774.
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Am J Nucl Med Mol Imaging. 2013 Jul 10;3(4):300-11. Print 2013.

Molecular MRI differentiation of VEGF receptor-2 levels in C6 and RG2 glioma models.

American journal of nuclear medicine and molecular imaging

Ting He, Nataliya Smith, Debra Saunders, Benjamin P Pittman, Megan Lerner, Stanley Lightfoot, Robert Silasi-Mansat, Florea Lupu, Rheal A Towner

Affiliations

  1. Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation Oklahoma City, OK 73104 USA ; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center Oklahoma City, OK 73104 USA.

PMID: 23901356 PMCID: PMC3715774

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 (gadolinium)-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.

Keywords: C6 and RG2 rat gliomas; Molecular magnetic resonance imaging (mMRI); fluorescence imaging; in vivo; vascular endothelial growth factor receptor 2 (VEGFR2)

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