Permeability to macromolecular contrast media quantified by dynamic MRI correlates with tumor tissue assays of vascular endothelial growth factor (VEGF).
Permeability to macromolecular contrast media quantified by dynamic MRI correlates with tumor tissue assays of vascular endothelial growth factor (VEGF).
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DOI：
10.1016/j.ejrad.2011.07.016
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发表时间：
2012-05
影响因子：
3.3
通讯作者：
Raatschen, Hans-Juergen
中科院分区：
文献类型：
--
作者：
Cyran, Clemens C.;Sennino, Barbara;Fu, Yanjun;Rogut, Victor;Shames, David M.;Chaopathomkul, Bundit;Wendland, Michael F.;McDonald, Donald M.;Brasch, Robert C.;Raatschen, Hans-Juergen
关键词：
将肿瘤中大分子内皮通透性的动态MRI测定与血管内皮生长因子（VEGF）的显微镜面密度测量相关联。该研究比较了来自两种不同的人癌细胞系MDA-MB-231肿瘤（n=5）和MDA-MB-435（n=8）的肿瘤异种移植物，据报道，这两种肿瘤分别表达较高和较低水平的VEGF。动态MRI增强的原型大分子造影剂（MMCM），白蛋白-（Gd-DTPA）35。采用二室动力学模型定量估计肿瘤微血管通透性（KPS; μl/min·100cm 3），并与每个肿瘤中VEGF的免疫组化测量结果相关联。MDA-MB-231肿瘤的平均KPS（KPS=58±30.9μl/min·100cm 3）是MDA-MB-435肿瘤（KPS=24±8.4μl/min·100cm 3）的2.4倍（p<0.05）。相应地，MDA-MB-231肿瘤中VEGF的面积密度（27.3± 2.2%，p<0.05）比MDA-MB-435癌症（10.5± 0.5%，p<0.05）大2.6倍。考虑所有肿瘤而不考虑细胞类型，在MRI估计的内皮渗透性和VEGF免疫反应性之间观察到显著的正相关性（r=0.67，p<0.05）。MRI检测内皮细胞对MMCM的通透性和肿瘤VEGF免疫反应性的相关性支持VEGF是癌症中大分子通透性增加的主要贡献者的假设。当临床应用时，MMCM增强MRI方法可以帮助优化VEGF抑制治疗在个体患者基础上的适当应用。
To correlate dynamic MRI assays of macromolecular endothelial permeability with microscopic area-density measurements of vascular endothelial growth factor (VEGF) in tumors. This study compared tumor xenografts from two different human cancer cell lines, MDA-MB-231 tumors (n=5), and MDA-MB-435 (n=8), reported to express respectively higher and lower levels of VEGF. Dynamic MRI was enhanced by a prototype macromolecular contrast medium (MMCM), albumin-(Gd-DTPA)35. Quantitative estimates of tumor microvascular permeability (KPS; μl/min·100cm3), obtained using a two-compartment kinetic model, were correlated with immunohistochemical measurements of VEGF in each tumor. Mean KPS was 2.4 times greater in MDA-MB-231 tumors (KPS=58±30.9μl/min·100cm3) than in MDA-MB-435 tumors (KPS=24±8.4μl/min·100cm) (p<0.05). Correspondingly, the area-density of VEGF in MDA-MB-231 tumors was 2.6 times greater (27.3±2.2%, p<0.05) than in MDA-MB-435 cancers (10.5±0.5%, p<0.05). Considering all tumors without regard to cell type, a significant positive correlation (r=0.67, p<0.05) was observed between MRI-estimated endothelial permeability and VEGF immunoreactivity. Correlation of MRI assays of endothelial permeability to a MMCM and VEGF immunoreactivity of tumors support the hypothesis that VEGF is a major contributor to increased macromolecular permeability in cancers. When applied clinically, the MMCM-enhanced MRI approach could help to optimize the appropriate application of VEGF-inhibiting therapy on an individual patient basis.
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