INSERM U836, Grenoble, France.
Radiology. 2010 Nov;257(2):342-52. doi: 10.1148/radiol.10092343. Epub 2010 Sep 9.
To evaluate the sequential injection of a low-molecular-weight (gadoterate meglumine [Gd-DOTA], 0.5 kDa) and a macromolecular (P846, 3.5 kDa) contrast media in monitoring the effect of antitumor therapies (antiangiogenic therapy and/or microbeam radiation therapy [MRT]) on healthy brain tissue and implanted tumors.
Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Eighty male rats bearing 9L gliosarcoma were randomized into four groups: untreated, antiangiogenic (sorafenib) therapy, MRT, and both treatments. Magnetic resonance (MR) imaging was performed 1 day before and 1, 5, and 8 days after the start of the treatment. At all time points, vascular integrity to a macromolecular contrast medium (P846) and, 11 minutes 30 seconds later, to low-molecular-weight contrast medium (Gd-DOTA) was evaluated by using a dynamic contrast material-enhanced MR imaging approach. To quantify vessel wall integrity, areas under the signal intensity curves were computed for each contrast medium. Unpaired t tests and one-way analysis of variance were used for statistical analyses.
Tumor vessels receiving antiangiogenic therapy became less permeable to the macromolecular contrast medium, but their permeability to the low-molecular-weight contrast medium remained unchanged. Healthy double-irradiated vessels became permeable to the low-molecular-weight contrast medium but not to the macromolecular contrast medium.
Antiangiogenic therapy and MRT generate different effects on the extravasation of contrast medium in tumoral and healthy tissues. This study indicates that the use of a low-molecular-weight contrast medium and a macromolecular contrast medium provides complementary information and suggests that the use of two contrast media within the same MR imaging session is feasible.
评估低分子量（钆喷酸葡胺[Gd-DOTA]，0.5 kDa）和大分子（P846，3.5 kDa）对比剂的顺序注射，以监测抗肿瘤治疗（抗血管生成治疗和/或微束放射治疗[MRT]）对健康脑组织和植入肿瘤的影响。
动物使用符合法国官方指南，并由当地动物福利和权益内部评估委员会进行评估。80 只携带 9L 神经胶质瘤肉瘤的雄性大鼠随机分为 4 组：未治疗组、抗血管生成（索拉非尼）治疗组、MRT 组和两种治疗组。在治疗开始前 1 天和开始后 1、5 和 8 天进行磁共振成像（MR）检查。在所有时间点，通过动态对比剂增强磁共振成像方法评估大分子对比剂（P846）和 11 分 30 秒后低分子量对比剂（Gd-DOTA）的血管完整性。为了量化血管壁完整性，计算了每种对比剂的信号强度曲线下面积。使用未配对 t 检验和单因素方差分析进行统计分析。
接受抗血管生成治疗的肿瘤血管对大分子对比剂的通透性降低，但对低分子量对比剂的通透性保持不变。健康的双重照射血管对低分子量对比剂具有通透性，但对大分子对比剂没有通透性。
抗血管生成治疗和 MRT 对肿瘤和健康组织中对比剂外渗产生不同的影响。这项研究表明，使用低分子量对比剂和大分子对比剂提供了互补的信息，并表明在同一磁共振成像检查中使用两种对比剂是可行的。
