Sun Xilin, Yang Lili, Yan Xuefeng, Sun Yingying, Zhao Dongliang, Ji Yang, Wang Kai, Chen Xiaoyuan, Shen Baozhong
Department of Radiology, the Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Molecular Imaging Research Center of Harbin Medical University, Harbin, Heilongjiang, China.
PLoS One. 2016 Sep 15;11(9):e0162601. doi: 10.1371/journal.pone.0162601. eCollection 2016.
Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Thirty MDA-MB-435 tumor mice were randomized into three groups: PBS control (C group), Abraxane only (A group), and sequential treatment with Abraxane followed by cisplatin (A-P group). Tumor volume was monitored based on caliper measurements. A DCE-MRI protocol was performed at baseline and day 3. The Ktrans, Kep and Ve were calculated and compared with CD31, α-SMA, and Ki67 histology data. Sequential treatment with Abraxane followed by cisplatin produced a significantly greater inhibition of tumor growth during the three weeks of the observation period. Decreases in Ktrans and Kep for the A and A-P groups were observed on day 3. Immunohistological staining suggested vascular remodeling during the Abraxane therapy. The changes in Ktrans and Kep values were correlated with alterations in the permeability of the tumor vasculature induced by the Abraxane treatment. In conclusion, Abraxane-mediated permeability variations in tumor vasculature can be quantitatively visualized by DCE-MRI, making this a useful method for studying the effects of early cancer treatment, especially the early vascular response. Vascular remodeling by Abraxane improves the efficiency of cisplatin delivery and thus results in a favorable treatment outcome.
我们之前的研究揭示了纳米白蛋白紫杉醇导致的肿瘤血管分子改变，从不成熟到成熟的改变不等，并证明整合素特异性PET示踪剂18F-FPPRGD2可用于无创监测此类变化。然而，肿瘤血管在灌注和通透性等功能水平上的变化对于监测癌症患者的纳米白蛋白紫杉醇治疗效果也很重要。本研究的目的是使用动态对比增强磁共振成像（DCE-MRI）进一步研究纳米白蛋白紫杉醇治疗期间的血管反应及其与顺铂协同相互作用的有效性。30只MDA-MB-435肿瘤小鼠被随机分为三组：PBS对照组（C组）、仅纳米白蛋白紫杉醇组（A组）和纳米白蛋白紫杉醇后序贯顺铂治疗组（A-P组）。基于卡尺测量监测肿瘤体积。在基线和第3天进行DCE-MRI方案。计算Ktrans、Kep和Ve，并与CD31、α-SMA和Ki67组织学数据进行比较。纳米白蛋白紫杉醇后序贯顺铂治疗在观察期的三周内对肿瘤生长产生了显著更大的抑制作用。在第3天观察到A组和A-P组的Ktrans和Kep降低。免疫组织化学染色表明纳米白蛋白紫杉醇治疗期间血管重塑。Ktrans和Kep值的变化与纳米白蛋白紫杉醇治疗诱导的肿瘤血管通透性改变相关。总之，纳米白蛋白紫杉醇介导的肿瘤血管通透性变化可通过DCE-MRI进行定量可视化，使其成为研究早期癌症治疗效果，尤其是早期血管反应的有用方法。纳米白蛋白紫杉醇引起的血管重塑提高了顺铂递送的效率，从而产生了良好的治疗效果。
