Center for Advanced Imaging Innovation and Research (CAI2R), Department of Radiology, New York University School of Medicine, New York, New York, United States of America.
Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, New York, United States of America.
PLoS One. 2020 Nov 25;15(11):e0241916. doi: 10.1371/journal.pone.0241916. eCollection 2020.
To investigate the feasibility of using diffusion MRI (dMRI) and dynamic contrast-enhanced (DCE) MRI to evaluate the treatment response of metronomic chemotherapy (MCT) in the 4T1 mammary tumor model of locally advanced breast cancer.
Twelve Balb/c mice with metastatic breast cancer were divided into treated and untreated (control) groups. The treated group (n = 6) received five treatments of anti-metabolite agent 5-Fluorouracil (5FU) in the span of two weeks. dMRI and DCE-MRI were acquired for both treated and control groups before and after MCT. Immunohistochemically staining and measurements were performed after the post-MRI measurements for comparison.
The control mice had significantly (p<0.005) larger tumors than the MCT treated mice. The DCE-MRI analysis showed a decrease in contrast enhancement for the control group, whereas the MCT mice had a more stable enhancement between the pre-chemo and post-chemo time points. This confirms the antiangiogenic effects of 5FU treatment. Comparing amplitude of enhancement revealed a significantly (p<0.05) higher enhancement in the MCT tumors than in the controls. Moreover, the MCT uptake rate was significantly (p<0.001) slower than the controls. dMRI analysis showed the MCT ADC values were significantly larger than the control group at the post-scan time point.
dMRI and DCE-MRI can be used as potential biomarkers for assessing the treatment response of MCT. The MRI and pathology observations suggested that in addition to the cytotoxic effect of cell kills, the MCT with a cytotoxic drug, 5FU, induced changes in the tumor vasculature similar to the anti-angiogenic effect.
探讨扩散磁共振成像（dMRI）和动态对比增强磁共振成像（DCE-MRI）用于评估节拍化疗（MCT）治疗局部晚期乳腺癌 4T1 乳腺肿瘤模型的治疗反应的可行性。
将 12 只患有转移性乳腺癌的 Balb/c 小鼠分为治疗组和未治疗组（对照组）。治疗组（n=6）在两周内接受 5 次抗代谢药物氟尿嘧啶（5FU）治疗。在 MCT 前后，对治疗组和对照组进行 dMRI 和 DCE-MRI 采集。在 MRI 后测量后进行免疫组化染色和测量，以进行比较。
对照组的肿瘤明显大于 MCT 治疗组（p<0.005）。DCE-MRI 分析显示对照组的对比增强明显降低，而 MCT 小鼠在化疗前和化疗后的时间点之间的增强更稳定。这证实了 5FU 治疗的抗血管生成作用。比较增强幅度显示，MCT 肿瘤的增强明显高于对照组（p<0.05）。此外，MCT 的摄取率明显慢于对照组（p<0.001）。dMRI 分析显示，在扫描后时间点，MCT 的 ADC 值明显大于对照组。
dMRI 和 DCE-MRI 可作为评估 MCT 治疗反应的潜在生物标志物。MRI 和病理学观察表明，除了细胞杀伤的细胞毒性作用外，MCT 联合细胞毒性药物 5FU 还可诱导肿瘤血管发生变化，类似于抗血管生成作用。
