Höink Anna, Persigehl Thorsten, Kwiecien Robert, Balthasar Martin, Mesters Rolf, Berdel Wolfgang, Heindel Walter, Bremer Christoph, Schwöppe Christian
Department of Clinical Radiology, University Hospital Münster, D-48149 Münster, Germany.
Department of Diagnostic and Interventional Radiology, University Hospital Cologne, D-50937 Cologne, Germany.
Oncol Lett. 2019 Jan;17(1):270-280. doi: 10.3892/ol.2018.9638. Epub 2018 Oct 29.
Truncated tissue factor (tTF)-NGR consists of the extracellular domain of the human TF and the binding motif NGR. tTF-NGR activates blood coagulation within the tumour vasculature following binding to CD13, and is overexpressed in the endothelial cells of tumour vessels, resulting in tumour vessel infarction and subsequent retardation/regression of tumour growth. The aim of the present study was to investigate gadofosveset-based real-time dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in evaluating the initial therapeutic effects of the anti-vascular tTF-NGR approach. DCE-MRI (3.0 T) was performed in human U87-glioblastoma tumour-bearing nude mice. During a dynamic T1w GE-sequence, a gadolinium-based blood pool contrast agent (gadofosveset) was injected via a tail vein catheter. Following the maximum contrast intensity inside the tumour being obtained, tTF-NGR was injected (controls received NaCl) and the contrast behaviour of the tumour was monitored by ROI analysis. The slope difference of signal intensities between controls and the tTF-NGR group was investigated, as well as the differences between the average area under the curve (AUC) of the two groups. The association between intensity, group (control vs. tTF-NGR group) and time was analysed by fitting a linear mixed model. Following the injection of tTF-NGR, the signal intensity inside the tumours exhibited a statistically significantly stronger average slope decrease compared with the signal intensity of the tumours in the NaCl group. Furthermore, the initial average AUC values of mice treated with tTF-NGR were 5.7% lower than the average AUC of the control animals (P<0.05). Gadofosveset-enhanced MRI enables the visualization of the initial tumour response to anti-vascular treatment in real-time. Considering the clinical application of tTF-NGR, this method may provide a simple alternative parameter for monitoring the tumour response to vascular disrupting agents and certain vascular targeting agents in humans.
截短型组织因子（tTF）-NGR由人组织因子的细胞外结构域和结合基序NGR组成。tTF-NGR与CD13结合后可激活肿瘤脉管系统内的血液凝固，且在肿瘤血管的内皮细胞中过表达，导致肿瘤血管梗死以及随后肿瘤生长的延缓/消退。本研究的目的是探讨基于钆弗塞特的实时动态对比增强磁共振成像（DCE-MRI）在评估抗血管tTF-NGR治疗方法的初始治疗效果中的应用。在荷人U87胶质母细胞瘤的裸鼠中进行了DCE-MRI（3.0 T）检查。在动态T1加权梯度回波序列期间，通过尾静脉导管注射一种基于钆的血池对比剂（钆弗塞特）。在获得肿瘤内的最大对比强度后，注射tTF-NGR（对照组注射氯化钠），并通过感兴趣区分析监测肿瘤的对比行为。研究了对照组和tTF-NGR组之间信号强度的斜率差异，以及两组曲线下平均面积（AUC）之间的差异。通过拟合线性混合模型分析强度、组（对照组与tTF-NGR组）和时间之间的关联。注射tTF-NGR后，与氯化钠组肿瘤的信号强度相比，肿瘤内的信号强度平均斜率下降在统计学上显著更强。此外，用tTF-NGR治疗的小鼠的初始平均AUC值比对照动物的平均AUC低5.7%（P<0.05）。钆弗塞特增强MRI能够实时观察到肿瘤对抗血管治疗的初始反应。考虑到tTF-NGR的临床应用，该方法可能为监测人类肿瘤对血管破坏剂和某些血管靶向剂的反应提供一个简单的替代参数。
