Feng Chen, Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
World J Gastroenterol. 2013 Dec 21;19(47):9092-103. doi: 10.3748/wjg.v19.i47.9092.
To explore whether the antitumor effect of a vascular disrupting agent (VDA) would be enhanced by combining with an antiangiogenic agent, and whether such synergistic effects can be effectively evaluated with separate calculation of diffusion weighted magnetic resonance imaging (DW-MRI).
Thirty-seven rats with implanted liver tumors were randomized into the following three groups: (1) ZD6126, a kind of VDA; (2) ZDTHA, ZD6126 in combination with an antiangiogenic, thalidomide; and (3) control. Morphological DW-MRI were performed and quantified before, 4 h and 2 d after treatment. The apparent diffusion coefficient (ADC) values were calculated separately for low b values (ADC(low)), high b values (ADC(high)) and all b values (ADC(all)). The tissue perfusion contribution, ADC(perf), was calculated as ADC(low)-ADC(high). Imaging findings were finally verified by histopathology.
The combination therapy with ZDTHA significantly delayed tumor growth due to synergistic effects by inducing cumulative tumor necrosis. In addition to delaying tumor growth, ZDTHA caused tumor necrosis in an additive manner, which was verified by HE staining. Although both ADC(high) and ADC(all) in the ZD6126 and ZDTHA groups were significantly higher compared to those in the control group on day 2, the entire tumor ADC(high) of ZDTHA was even higher than that of ZD6126, but the significant difference was not observed for ADC(all) between ZDTHA and ZD6126. This indicated that the perfusion insensitive ADC(high) values calculated from high b value images performed significantly better than ADC(all) for the monitoring of tumor necrosis on day 2. The perfusion sensitive ADC(perf) derived from ADC(low) by excluding high b value effects could better reflect the reduction of blood flow due to the vessel shutdown induced by ZD6126, compared to the ADC(low) at 4 h. The ADC(perf) could provide valuable perfusion information from DW-MRI data.
The separate calculation of ADC is more useful than conventional averaged ADC in evaluating the efficacy of combination therapy with ZD6126 and thalidomide for solid tumors.
探讨血管破坏剂（VDA）与抗血管生成药物联合应用是否能增强抗肿瘤作用，以及是否可以通过单独计算扩散加权磁共振成像（DW-MRI）来有效评估这种协同作用。
将 37 只植入肝癌的大鼠随机分为三组：（1）ZD6126，一种 VDA；（2）ZDTHA，ZD6126 联合抗血管生成药物沙利度胺；（3）对照组。治疗前、治疗后 4 h 和 2 d 进行形态学 DW-MRI 检查并进行定量分析。分别计算低 b 值（ADC(low))、高 b 值（ADC(high))和全 b 值（ADC(all))的表观扩散系数（ADC）值。组织灌注贡献，ADC(perf)，计算为 ADC(low)-ADC(high)。最终通过组织病理学验证影像学发现。
ZDTHA 联合治疗由于协同作用导致肿瘤累积坏死而显著延迟肿瘤生长。除了延迟肿瘤生长外，ZDTHA 还以附加方式引起肿瘤坏死，这通过 HE 染色得到了验证。尽管 ZD6126 和 ZDTHA 组在第 2 天的 ADC(high)和 ADC(all)均显著高于对照组，但 ZDTHA 整个肿瘤的 ADC(high)甚至高于 ZD6126，但 ZDTHA 与 ZD6126 之间的 ADC(all)无显著差异。这表明，高 b 值图像计算的灌注不敏感 ADC(high)值在监测第 2 天肿瘤坏死方面优于 ADC(all)。通过排除高 b 值影响从 ADC(low)中得出的灌注敏感 ADC(perf)，可以更好地反映 ZD6126 诱导的血管关闭引起的血流减少，与 4 h 时的 ADC(low)相比。ADC(perf)可以从 DW-MRI 数据中提供有价值的灌注信息。
与常规平均 ADC 相比，单独计算 ADC 更有助于评估 ZD6126 和沙利度胺联合治疗实体瘤的疗效。
