Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model

Purpose: To examine dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a macromolecular contrast agent (P792) to visualize effects of radiotherapy (RT) on microvascular leakage in a colorectal cancer model. Methods and Materials: CC531 tumors were induced in WAG/Rij rats. DCE-MRI was performed before and 5 days after 5 x 5 Gy of RT and parametric maps generated of the endothelial transfer constant (K-trans) and the fractional interstitial space (V-e) according to the Tofts model. Tissue pO(2) mapping was performed in each tumor core and rim before and after RT. Microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, and pimonidazole hypoxia staining were compared with a control group of tumor-bearing rats. Results: Mean K-trans and v(c) were significantly reduced after RT in all tumor regions. Mean pO(2) was 6.8 mm Hg before-RT vs. 7.7 mm Hg after RT (p<0.001) in the tumor rim and 3.5 mm Hg before RT vs. 4.4 mm Hg after RT (p<0.001) in the tumor core. Mean MVD in the tumor rim was 10.4 in the RT treated group vs. 16.9 in the control group (p=0.061). VEGF expression was significantly higher in RT-treated rats. After RT, no correlation was found between DCE-MRI parameters and histologic parameters. A correlation was seen after RT between pO(2) and K-trans (r=-0.57, p=0.08) and between pO(2) and v, (r=-0.65, p=0.04). Conclusions: Dynamic contrast-enhanced-MRI with P792 allows quantification of microvascular changes in this colorectal model. RT significantly reduces neovascular leakage and enhances tissue oxygenation and VEGF expression. After RT, DCE-MRI parameters are related to tumor pO(2), but not to MVD or VEGF expression. (C) 2006 Elsevier Inc.