Ceelen Wim, Smeets Peter, Backes Walter, Van Damme Nancy, Boterberg Tom, Demetter Pieter, Bouckenooghe Isabel, De Visschere Marieke, Peeters Marc, Pattyn Piet
Department of Surgery, Ghent University Hospital, Ghent, Belgium.
Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1188-96. doi: 10.1016/j.ijrobp.2005.10.026. Epub 2006 Feb 2.
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.
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 (Ve) according to the Tofts model. Tissue pO2 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.
Mean K(trans) and v(e) were significantly reduced after RT in all tumor regions. Mean pO2 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 pO2 and K(trans) (r = -0.57, p = 0.08) and between pO2 and v(e) (r = -0.65, p = 0.04).
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 pO2, but not to MVD or VEGF expression.
使用大分子造影剂（P792）进行动态对比增强磁共振成像（DCE-MRI），以观察放疗（RT）对结直肠癌模型中微血管渗漏的影响。
在WAG/Rij大鼠中诱导产生CC531肿瘤。在5×5 Gy放疗前和放疗后5天进行DCE-MRI，并根据Tofts模型生成内皮转运常数（K(trans)）和组织间隙分数（Ve）的参数图。在放疗前后对每个肿瘤核心和边缘进行组织pO2映射。将微血管密度（MVD）、血管内皮生长因子（VEGF）表达和匹莫硝唑缺氧染色与荷瘤大鼠对照组进行比较。
放疗后所有肿瘤区域的平均K(trans)和v(e)均显著降低。肿瘤边缘放疗前平均pO2为6.8 mmHg，放疗后为7.7 mmHg（p < 0.001）；肿瘤核心放疗前平均pO2为3.5 mmHg，放疗后为4.4 mmHg（p < 0.001）。放疗组肿瘤边缘的平均MVD为10.4，对照组为16.9（p = 0.061）。放疗大鼠的VEGF表达明显更高。放疗后，DCE-MRI参数与组织学参数之间未发现相关性。放疗后pO2与K(trans)之间存在相关性（r = -0.57，p = 0.08），pO2与v(e)之间也存在相关性（r = -0.65，p = 0.04）。
使用P792进行动态对比增强MRI可对该结直肠癌模型中的微血管变化进行量化。放疗可显著减少新生血管渗漏，增强组织氧合和VEGF表达。放疗后，DCE-MRI参数与肿瘤pO2相关，但与MVD或VEGF表达无关。
