Tumor microvascular changes in antiangiogenic treatment: Assessment by magnetic resonance contrast media of different molecular weights
Tumor microvascular changes in antiangiogenic treatment: Assessment by magnetic resonance contrast media of different molecular weights
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DOI：
10.1002/jmri.20049
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发表时间：
2004-07-01
影响因子：
4.4
通讯作者：
Roberts, TPL
中科院分区：
文献类型：
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作者：
Turetschek, K;Preda, A;Roberts, TPL
目的：在实验性肿瘤治疗模型中，测试不同分子量(MWs)磁共振造影剂对非侵袭性微血管改变的表征能力。材料和方法：将分化较差的人乳腺癌细胞系MD-MBA-435植入31只雌性纯合裸鼠体内。动物被随机分配到对照组(生理盐水)或药物处理组(单抗血管内皮生长因子(MabVEGF)抗体)。在两组动物中，每只动物在基线和后续检查中连续几天使用多达三种不同的造影剂进行动态磁共振成像(MRI)。所用造影剂的相对分子质量为557~92 kDa。使用双向动力学模型，评估每种造影剂的肿瘤微血管特征，包括血浆体积分数(FPV)和跨内皮细胞渗透性K-PS。结果：药物治疗组肿瘤生长明显慢于对照组(P<；0.0005)。与使用中间或大分子造影剂(MMCM)的基础值相比，单抗-血管内皮生长因子抗体治疗组的平均K-PS和FPV值显著降低(P<；0.05)，但使用小分子造影剂(SMCM)时，K-PS和FPV值没有显著变化。在对照组中，任何造影剂的平均K-PS和平均FPV值均未达到统计学意义。结论：动态MRI可以监测单抗-血管内皮生长因子抗体对肿瘤微血管特征的治疗效果。中等大小的药物，如Gadmer-17，提供了相当大的动态范围，并且较少受到成像精度的限制，因此应该被认为是临床上监测抗血管生成治疗效果的实用替代方案。
Purpose: To test magnetic resonance (MR) contrast media of different molecular weights (MWs) for their potential to characterize noninvasively microvascular changes in an experimental tumor treatment model.Materials and Methods: MD-MBA-435, a poorly differentiated human breast cancer cell line, was implanted into 31 female homozygous athymic rats. Animals were assigned randomly to a control (saline) or drug treatment (monoclonal antibody vascular endothelial growth factor (MabVEGF) antibody) group. In both groups, dynamic MR imaging (MRI) was performed in each animal using up to three different contrast media on sequential days at baseline and follow-up examination. The MWs of the contrast media used ranged from 557 Da to 92 kDa. Using a bidirectional kinetic model, tumor microvessel characteristics, including the fractional plasma volume (fPV) and transendothelial permeability K-PS, were estimated for each contrast medium. These microvascular characteristics were compared between drug and control groups and between contrast media of different MWs.Results: Tumors grew significantly slower (P < 0.0005) in the drug treatment group than in the control group. Mean K-PS and fPV values decreased significantly (P < 0.05) in the Mab-VEGF antibody-treated group compared to baseline values using intermediate or macromolecular contrast media (MMCM), but did not change significantly using small molecular contrast media (SMCM). In the control groups, mean K-PS and mean fPV values did not reach statistical significance for any of the contrast media used.Conclusion: Therapeutic effects of a Mab-VEGF antibody on tumor microvessel characteristics can be monitored by dynamic MRI. Intermediate-size agents, such as Gadomer-17, offer a substantial dynamic range and are less limited by imaging precision and therefore should be considered a practical alternative to monitor antiangiogenesis treatment effects in a clinical setting.