| 熊青青,段玉梅,杨朝炳,王云玲,贾文霄.动态增强MR定量监测血管靶向药物治疗结肠癌移植瘤[J].中国医学影像技术,2016,32(6):849~853 |
| 动态增强MR定量监测血管靶向药物治疗结肠癌移植瘤 |
| Dynamic contrast-enhanced MRI in evaluation on early effects of vascular-targeted agents in treatment of colon cancer xenografts |
| 投稿时间：2015-10-21 修订日期：2016-01-12 |
| DOI：10.13929/j.1003-3289.2016.06.009 |
| 中文关键词: 磁共振成像 结肠肿瘤 微血管密度 肿瘤种植 |
| 英文关键词:Magnetic resonance imaging Colonic neoplasms Microvessel density Neoplasms seeding |
| 基金项目: |
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| 摘要点击次数: 2077 |
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| 中文摘要: |
| 目的 应用动态增强MR(DCE-MRI)参数定量监测血管靶向类药物治疗结肠癌移植瘤的早期效果。方法 将36只接种人结肠癌HT-29细胞的裸鼠按随机数字法等分为3组,并分别腹腔注射贝伐单抗(抗血管生成药物组,10 mg/kg体质量)、考布他汀(血管破坏剂组,100 mg/kg体质量)和0.9%氯化钠溶液(对照组,100 mg/kg体质量)。分别于给药前和给药后1、24、48 h对实验动物行DCE-MRI扫描,分析传输常数(Ktrans)、回流常量(Kep)、血管外细胞外容积分数(Ve)和增强曲线下初始面积(iAUC)。每次扫描完成后各组随机处死2只裸鼠,行HE染色及免疫组织化学染色检测瘤体微血管密度(MVD)。DCE-MRI参数组间及组内不同时间的比较行方差分析;DCE-MRI参数与MVD间的关系行Pearson相关性分析。结果 裸鼠皮下结肠癌移植瘤瘤体边缘区域DCE-MRI呈显著的渐进性强化,呈高灌注,中心区域强化幅度较低,呈现低灌注改变;抗血管生成药物组和血管破坏剂组不同时间点Ktrans及Kep值差异均有统计学意义(P均<0.05);对照组肿瘤的Ktrans值差异无统计学意义(P=0.60),Kep值差异均有统计学意义(P=0.01);Ktrans和Kep值治疗前组间比较差异均无统计学意义(P均>0.05)。治疗后1、24、48 h,相同时间Ktrans和Kep值3组间比较差异均有统计学意义(P均<0.05);不同时间点抗血管生成药物组Ve值差异有统计学意义(P=0.03),治疗后24 h组间比较Ve和iAUC值差异均有统计学意义(P均<0.05);抗血管生成药物组和血管破坏剂组坏死较对照组明显,血管内皮较对照组稀疏。MVD计数与Ktrans和Kep值呈正相关(r=0.66、0.71, P均<0.05)。结论 DCE-MRI参数Ktrans和Kep能及时准确地监测到肿瘤血管靶向药物治疗后的效果,或可指导临床方案的制定。 |
| 英文摘要: |
| Objective To monitor early response of colon cancer xenografts in nude mice using dynamic contrast-enhanced MRI (DCE-MRI). Methods Thirty six nude mice were injected subcutaneously with human colon cancer cells HT-29 to the right hind leg. The nude mice were evenly divided into anti-angiogenesis drug group (n=12, treating with bevacizumab 10 mg/kg), tumor vascular-disrupting agent group (n=12, treating with combretastatin 100 mg/kg) and control group (n=12, treating with the normal saline 100 mg/kg). DCE-MRI was performed before medication and 1, 24 and 48 h after medication. The transfer constant (Ktrans),rate constant (Kep), tumor extravascular extracellular space volume (Ve) and initial area under enhancement curve (iAUC) of DCE-MRI were analyzed. Then every two tumors were harvested and underwent pathology examination each time, including HE staining and microvessel density (MVD). The DCE-MRI parameters were analyzed using repeated measures analysis of variance (RMANOVA). The Pearson correlation coefficient was used to analyze the correlation between parameters of DCE-MRI and MVD. Results Under DCE-MRI, the edge of subcutaneous colon cancer xenografts was obviously gradually enhanced, high perfusion, and the strength degree of the central region was low and low perfusion. The differences in Ktrans and Kep values of different time in anti-angiogenesis drug group and tumor vascular-disrupting agent group were statistically significant (all P<0.05). The Ktrans had no significant difference (P=0.60) and the Kep had significant difference in control group (P=0.01). There was no significant difference in Ktrans and Kep before medication in different groups (all P>0.05). There were significant difference in Ktrans and Kep at 1 h, 24 h, 48 h after medication among different groups (all P<0.05). The Ve value of anti-angiogenesis drug group had significant difference in different times (P=0.03). There were significant difference of the Ve and iAUC at 24 h after medication among different groups (all P<0.05). MVD of anti-angiogenesis drug group and tumor vascular-disrupting agent group were lower than of control group. Ktrans and Kep were positively correlated with MVD (r=0.64, 0.71, both P<0.05). Conclusion Ktrans and Kep of DCE-MRI are sensitive to monitor the change of microcirculation perfusion and capillary permeability. Ktrans and Kep are positively correlation with the MVD, may be used in monitoring the earlier effects of vascular-targeted agents in targeted therapy for colon cancer. |
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