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分子影像学在预测肾癌靶向治疗反应中的应用。

Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma.

机构信息

IR4M, UMR 8081, Paris-Sud University, CNRS, Bâtiment 220, rue Ampère, 91405 Orsay Cedex, France.

Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France.

出版信息

Contrast Media Mol Imaging. 2017 Apr 9;2017:7498538. doi: 10.1155/2017/7498538. eCollection 2017.

Abstract

Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting v3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations Δ2, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular v3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI ( = 0.87, = 0.0003) and AUC ( = 0.81, = 0.0013). The percentage of vessel tissue area was significantly reduced ( < 0.01) in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or v3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.

摘要

针对参与新生血管形成的内皮整合素的分子磁共振成像与 DCE-US 和免疫化学进行了比较,以评估三种不同治疗药物在肾细胞癌中的早期反应。将人 A498 肾癌细胞皮下接种到 24 只裸鼠中。在 4 天内,小鼠接受磷酸盐缓冲液、舒尼替尼、依维莫司或贝伐珠单抗治疗。在治疗开始后 4 天进行基线和 DCE-US 以及靶向 v3 的分子 MRI。比较 PI、AUC、弛豫率变化 Δ2 和 CD31 染色微血管量化的血管面积百分比。DCE-US 测量的 PI 和 AUC 参数在贝伐珠单抗组中观察到明显降低,而分子 v3 靶向 MRI 能够检测到贝伐珠单抗和依维莫司组的明显变化。CD31 染色微血管的百分比与 DCE-US 参数 PI( = 0.87, = 0.0003)和 AUC( = 0.81, = 0.0013)显著相关。在舒尼替尼和贝伐珠单抗组中,血管组织面积的百分比均显著降低( < 0.01)。我们报告了使用 DCE-US 或 v3 靶向 MRI 诱导靶向治疗后新生血管形成修饰的早期检测。我们认为这些结果应该鼓励临床试验的发展,以进一步评估这种分子 MRI 技术的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1528/5612742/56ed2d182e97/CMMI2017-7498538.001.jpg

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