Raatschen Hans-Juergen, Fischer Susanne, Zsivcsec Benjamin, Schoenfeld Christian-Olaf, Hotz Birgit, Buhr Heinz J, Hotz Hubert G
Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
Acta Radiol. 2014 Mar;55(2):131-9. doi: 10.1177/0284185113493776. Epub 2013 Jul 26.
Currently, early changes of tumor vasculature after angiogenesis inhibition can only be evaluated by histopathology, a method not suitable in a clinical setting.
To quantify effects of different angiogenesis inhibitors on the microvasculature of orthotopically implanted pancreatic cancers by contrast-enhanced magnetic resonance imaging (MRI) in order to establish a non-invasive technique for monitoring antiangiogenic cancer treatment.
DSL-6A/C1 pancreatic cancers were implanted in the pancreas of 109 Lewis rats. Three weeks later, antiangiogenic treatment was initiated by administration of Bevacizumab (n = 38) or Suramin (n = 27) while the control group (n = 44) remained untreated. Dynamic MRI was performed 24 h, 1 week, and 4 weeks after treatment initiation. Fractional tumor plasma volume (fPV, %) and vascular permeability (K(PS), mL/min/100 cc) were calculated based on the MRI data by using a pharmacokinetic model.
Twenty-four hours after the initial dose, a significant decline in K(PS) was observed in the Bevacizumab group compared to the control and Suramin group (0.002 ± 0.008; 0.057 ± 0.046 and 0.064 ± 0.062 (mean ± SD); P < 0.05). At 1 week, fPV was significantly smaller in Bevacizumab and Suramin treated tumors compared to control tumors (6.25 ± 2.74, 7.47 ± 3.44, and 15.10 ± 9.97, respectively; P < 0.05). Differences in tumor volumes were first observed after 4 weeks of treatment with significantly larger control tumors (4380.3 ± 1590.6 vs. 869.6 ± 717.2 and 1676.5 ± 2524.1 mm(3); P < 0.05).
Dynamic MRI can quantify antiangiogenic effects on tumor microvasculature before changes in tumor volumes are detectable. Thus, this technique is a reasonable addition to morphological MRI and may be applied as an alternative to histopathology.
目前，血管生成抑制后肿瘤血管的早期变化只能通过组织病理学评估，而该方法不适用于临床环境。
通过对比增强磁共振成像（MRI）量化不同血管生成抑制剂对原位植入胰腺癌微血管的影响，以建立一种监测抗血管生成癌症治疗的非侵入性技术。
将DSL-6A/C1胰腺癌植入109只Lewis大鼠的胰腺中。三周后，通过给予贝伐单抗（n = 38）或苏拉明（n = 27）开始抗血管生成治疗，而对照组（n = 44）未接受治疗。在开始治疗后24小时、1周和4周进行动态MRI检查。使用药代动力学模型根据MRI数据计算肿瘤血浆分数体积（fPV，%）和血管通透性（K(PS)，mL/min/100 cc）。
初始剂量后24小时，与对照组和苏拉明组相比，贝伐单抗组的K(PS)显著下降（0.002±0.008；0.057±0.046和0.064±0.062（平均值±标准差）；P < 0.05）。在1周时，与对照肿瘤相比，贝伐单抗和苏拉明治疗的肿瘤中的fPV显著更小（分别为6.25±2.74、7.47±3.44和15.10±9.97；P < 0.05）。在治疗4周后首次观察到肿瘤体积的差异，对照肿瘤明显更大（4380.3±1590.6 vs. 869.6±717.2和1676.5±2524.1 mm(3)；P < 0.05）。
动态MRI可以在肿瘤体积变化可检测之前量化对肿瘤微血管的抗血管生成作用。因此，该技术是形态学MRI的合理补充，可作为组织病理学的替代方法应用。
