Pharmacokinetic Modeling of Targeted Ultrasound Contrast Agents for Quantitative Assessment of Anti-Angiogenic Therapy: a Longitudinal Case-Control Study in Colon Cancer.
Pharmacokinetic Modeling of Targeted Ultrasound Contrast Agents for Quantitative Assessment of Anti-Angiogenic Therapy: a Longitudinal Case-Control Study in Colon Cancer.
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用于定量评估抗血管生成治疗的靶向超声造影剂的药代动力学模型：结肠癌的纵向病例对照研究。
DOI：
10.1007/s11307-018-1274-z
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发表时间：
2019
影响因子：
3.1
通讯作者：
Mischi,Massimo
中科院分区：
文献类型：
--
作者：
Turco,Simona;ElKaffas,Ahmed;Zhou,Jianhua;Lutz,AmelieM;Wijkstra,Hessel;Willmann,JürgenK;Mischi,Massimo
目的评价定量和半定量超声分子成像（USMI）在人结肠癌小鼠移植瘤抗血管生成治疗监测中的应用。方法通过注射LS 174 T（Nr= 9）或CT 26（Nn= 8）癌细胞分别模拟临床反应者和无反应者，在17只小鼠中建立结肠癌。在第0、3和7天施用抗血管生成治疗（贝伐单抗;Nrt=Nnt= 5）或对照治疗（盐水;Nrc= 4，Nnc= 3）。通过在第0、1、3、7和10天注射靶向血管内皮生长因子受体2（VEGFR 2）的微泡进行三维USMI。每天比较通过首过结合模型拟合估计的微泡结合率（kb）和半定量参数晚期增强（LE）和差异靶向增强（dTE），以评价其评估和预测治疗反应的能力。相关性分析与离体免疫组织化学定量VEGFR 2表达和血管面积的百分比也performed. ResultsUSMI参数在治疗过程中的显着变化，观察只有在与贝伐单抗治疗的反应（P值< 0.05）。通过定量参数kb（p值< 0.01），早在治疗后1天就可以预测对治疗的反应，这比肿瘤体积定量可能的时间要早。USMI参数可以显著区分临床应答者和无应答者（p值< 0.01），并与VEGFR 2表达和血管面积百分比的体外定量相关（p值<< 0.01）。结论USMI（半）定量参数提供了与肿瘤体积相比对治疗反应的早期评估，允许早期预测无反应者，并与离体血管生成生物标志物密切相关。
PurposeTo evaluate quantitative and semi-quantitative ultrasound molecular imaging (USMI) for antiangiogenic therapy monitoring in human colon cancer xenografts in mice.ProceduresColon cancer was established in 17 mice by injection of LS174T (Nr= 9) or CT26 (Nn= 8) cancer cells to simulate clinical responders and non-responders, respectively. Antiangiogenic treatment (bevacizumab;Nrt=Nnt= 5) or control treatment (saline;Nrc= 4,Nnc= 3) was administered at days 0, 3, and 7. Three-dimensional USMI was performed by injection at days 0, 1, 3, 7, and 10 of microbubbles targeted to the vascular endothelial growth factor receptor 2 (VEGFR2). Microbubble binding rate (kb), estimated by first-pass binding model fitting, and semi-quantitative parameters late enhancement (LE) and differential targeted enhancement (dTE) were compared at each day to evaluate their ability to assess and predict the response to therapy. Correlation analysis with theex-vivoimmunohistological quantification of VEGFR2 expression and the percentage blood vessel area was also performed.ResultsSignificant changes in the USMI parameters during treatment were observed only in the responders treated with bevacizumab (p-value < 0.05). Prediction of the response to therapy as early as 1 day after treatment was achieved by the quantitative parameterkb(p-value < 0.01), earlier than possible by tumor volume quantification. USMI parameters could significantly distinguish between clinical responders and non-responders (p-value << 0.01) and correlated well with theex-vivoquantification of VEGFR2 expression and the percentage blood vessels area (p-value << 0.01).ConclusionUSMI (semi)quantitative parameters provide earlier assessment of the response to therapy compared to tumor volume, permit early prediction of non-responders, and correlate well withex-vivoangiogenesis biomarkers.
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10.7326/0003-4819-96-2-263_3
发表时间：
1984
期刊：
Classical Review
影响因子：
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158.5
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1984
期刊：
Classical Review
影响因子：
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W. M. Gordon