Center for Pharmaceutical and Molecular Imaging, Department of Radiology, University of California San Francisco, Box 0628, 505 Parnassus Ave, San Francisco, CA 94143-0628, United States.
Eur J Radiol. 2012 May;81(5):891-6. doi: 10.1016/j.ejrad.2011.07.016. Epub 2011 Sep 1.
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 (K(PS); μl/min × 100 cm(3)), obtained using a two-compartment kinetic model, were correlated with immunohistochemical measurements of VEGF in each tumor.
Mean K(PS) was 2.4 times greater in MDA-MB-231 tumors (K(PS)=58 ± 30.9 μl/min × 100 cm(3)) than in MDA-MB-435 tumors (K(PS)=24 ± 8.4 μl/min × 100 cm(3)) (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.
将大分子内皮通透性的动态 MRI 检测与肿瘤中血管内皮生长因子（VEGF）的微观面积密度测量相关联。
本研究比较了两种不同的人源癌细胞系的肿瘤异种移植物，MDA-MB-231 肿瘤（n=5）和 MDA-MB-435（n=8），前者报告表达更高水平的 VEGF，后者报告表达更低水平的 VEGF。通过原型大分子对比剂（MMCM）白蛋白-（Gd-DTPA）35 增强动态 MRI。使用双室动力学模型获得的肿瘤微血管通透性（K（PS）；μl/min×100 cm3）定量估计值与每个肿瘤中的 VEGF 的免疫组织化学测量相关联。
在 MDA-MB-231 肿瘤（K（PS）=58±30.9μl/min×100 cm3）中，平均 K（PS）比 MDA-MB-435 肿瘤（K（PS）=24±8.4μl/min×100 cm3）高 2.4 倍（p<0.05）。相应地，在 MDA-MB-231 肿瘤中 VEGF 的面积密度高 2.6 倍（27.3±2.2%，p<0.05），而在 MDA-MB-435 癌症中则低 0.5%（10.5±0.5%，p<0.05）。考虑到所有肿瘤而不考虑细胞类型，MRI 估计的内皮通透性与 VEGF 免疫反应性之间观察到显著的正相关（r=0.67，p<0.05）。
将内皮通透性的 MRI 检测与 MMCM 和肿瘤 VEGF 免疫反应性相关联，支持 VEGF 是癌症中大分子通透性增加的主要贡献者的假说。当应用于临床时，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。
