He Ting, Smith Nataliya, Saunders Debra, Pittman Benjamin P, Lerner Megan, Lightfoot Stanley, Silasi-Mansat Robert, Lupu Florea, Towner Rheal A
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.
Am J Nucl Med Mol Imaging. 2013 Jul 10;3(4):300-11. Print 2013.
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.
血管内皮生长因子受体2（VEGFR2）是一种在胶质瘤中过度表达的重要血管生成标志物。通过分子磁共振成像（mMRI），可以在体内对血管生成不同的啮齿动物胶质瘤中VEGFR2的不同水平进行表征。通过向携带C6或RG2胶质瘤的大鼠静脉注射抗VEGFR2探针（抗VEGFR2-白蛋白-钆（Gd）-二乙三胺五乙酸（DTPA）-生物素）来评估VEGFR2水平，并用mMRI进行可视化。将非特异性IgG与白蛋白-Gd-DTPA-生物素构建体偶联作为造影剂分子量对照。VEGFR2水平在C6胶质瘤的不同区域是异质性的，而在RG2胶质瘤中VEGFR2分布更均匀。与C6胶质瘤相比，RG2胶质瘤在肿瘤周边和坏死周围区域（p<0.05）的VEGFR2较少，但在肿瘤内部区域（p<0.01）的VEGFR2较多。mMRI结果通过荧光染色和切除的胶质瘤及脑组织中抗VEGFR2探针的平均荧光强度（MFI）定量得到证实，以及在C6和RG2胶质瘤及相应对侧脑组织中检测VEGFR2。发现与RG2肿瘤相比，C6胶质瘤中的离体VEGFR2水平显著更高（p<0.001），这与使用VEGFR2探针的体内检测结果一致。与血管生成相关的缺氧诱导因子1α（HIF-1α）的免疫组织化学染色表明，与C6胶质瘤相比，RG2中的HIF-1α水平更高（p<0.01）。数据表明，与RG2胶质瘤相比，C6胶质瘤的血管生成更多地与肿瘤周边和坏死周围区域的大血管相关，而肿瘤内部的微血管生成较少。
