Permeability to macromolecular contrast media quantified by dynamic MRI correlates with tumor tissue assays of vascular endothelial growth factor (VEGF)

Purpose: To correlate dynamic MRI assays of macromolecular endothelial permeability with microscopic area-density measurements of vascular endothelial growth factor (VEGF) in tumors. Methods and material: 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; mu l/min x 100 cm(3)), obtained using a two-compartment kinetic model, were correlated with immunohistochemical measurements of VEGF in each tumor. Results: Mean K-PS was 2.4 times greater in MDA-MB-231 tumors (K-PS = 58 +/- 30.9 mu l/min x 100 cm(3)) than in MDA-MB-435 tumors (K-PS = 24 +/- 8.4 mu l/min x 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. Conclusion: 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.