Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Tissue Eng Part A. 2010 Feb;16(2):357-64. doi: 10.1089/ten.TEA.2009.0233.
In tissue engineering it is often necessary to assess angiogenesis associated with engineered tissue grafts. The levels of vascular endothelial growth factor receptor 2 (VEGF-R2) is elevated during angiogenesis. The goal of this study was to develop and assess a novel magnetic resonance imaging (MRI) molecular probe for the in vivo detection of VEGF-R2 in an experimental rodent model of disease. The possible use of the probe in tissue engineering applications is discussed. The molecular targeting agent we used in our study incorporated a magnetite-based dextran-coated nanoparticle backbone covalently bound to an anti-VEGF-R2 antibody. We used molecular MRI with an anti-VEGF-R2 probe to detect in vivo VEGF-R2 levels as a molecular marker for gliomas (primary brain tumors). Tumor regions were compared with normal tissue. Nonimmune nonspecific normal rat immunoglobulin G coupled to the dextran-coated nanoparticles was used as a control. Prussian blue staining for iron-based nanoprobes was used to confirm the specificity of the probe for VEGF-R2 in glioma tissue. VEGF-R2 levels in tumor tissues were also confirmed in western blots and via immunohistochemistry. Based on our results, in vivo evaluation of tissue angiogenesis using molecular MRI is possible in tissue engineering applications.
在组织工程中，经常需要评估与工程组织移植物相关的血管生成。血管内皮生长因子受体 2（VEGF-R2）的水平在血管生成过程中升高。本研究的目的是开发和评估一种新型的磁共振成像（MRI）分子探针，用于在疾病的实验性啮齿动物模型中体内检测 VEGF-R2。讨论了该探针在组织工程应用中的可能用途。我们在研究中使用的分子靶向剂包含一个基于磁铁矿的葡聚糖涂层纳米颗粒骨干，通过共价键与抗 VEGF-R2 抗体结合。我们使用抗 VEGF-R2 探针进行分子 MRI，以检测作为脑胶质瘤（原发性脑肿瘤）分子标志物的体内 VEGF-R2 水平。将肿瘤区域与正常组织进行比较。将与葡聚糖涂层纳米颗粒偶联的非免疫非特异性正常大鼠免疫球蛋白 G 用作对照。普鲁士蓝染色用于铁基纳米探针，以确认探针在胶质瘤组织中对 VEGF-R2 的特异性。还通过 Western blot 和免疫组织化学证实了肿瘤组织中的 VEGF-R2 水平。基于我们的结果，使用分子 MRI 对组织血管生成进行体内评估在组织工程应用中是可行的。
