能谱CT评价贝伐单抗抗大鼠C6胶质瘤血管生成效果

目的 探讨能谱CT定量参数评估贝伐单抗抗大鼠C6胶质瘤血管生成疗效的可行性及价值。方法 对30只SD大鼠颅内注射C6细胞悬液，建立脑胶质瘤模型。于造模后2周（用药前）行能谱CT观察成瘤情况，并随机分为实验组和对照组，每日分别腹腔注射贝伐单抗注射液5 mg/kg及同等剂量浓度0.9%生理盐水，持续1周。分别于用药第4、8天行能谱CT扫描，测量并比较用药前及用药4、8天肿瘤40~140 keV单能量CT值及碘含量。每次扫描结束后于2组中随机各取3只大鼠，处死后对全脑组织行HE染色及血管内皮生长因子（VEGF）免疫组化染色，比较组间不同时间点VEGF阳性细胞数量的差异，分析能谱CT定量参数与VEGF阳性细胞数量的相关性。结果 共26只大鼠纳入研究，实验组及对照组各13只。用药前2组70 keV单能量CT值及碘浓度差异无统计学意义（t=1.35、-0.99，P均>0.05）；用药第4天及第8天实验组70 keV单能量CT值及碘浓度均低于对照组（t=-3.56、-6.42及-6.43、-13.01，P均<0.05）。用药前2组阳性细胞百分比差异无统计学意义（P=0.11），第4、8天实验组阳性细胞百分比（33.93%、25.00%）低于对照组（53.28%、63.80%，P均<0.05）。实验组及对照组不同时间点70 keV单能量CT值及碘浓度与VEGF均呈正相关（P均<0.05）。结论 能谱CT多参数成像可用于评估贝伐单抗抗大鼠C6脑胶质瘤血管生成疗效，有望成为评价抗肿瘤血管生成药物疗效的新方法。

Energy spectral CT in evaluation on efficacy of Bevacizumab against angiogenesis in rat models of C6 glioma

Objective To explore the feasibility and value of quantitative parameters of energy spectral CT for evaluating the efficacy of Bevacizumab against angiogenesis of C6 glioma rat models. Methods C6 glioma rat models were established through intracranial injection of C6 cell suspension in 30 SD rats. The tumor formation was observed with energy spectrum CT 2 weeks after modeling (day 0). The rats were randomly divided into experimental group and control group and given celiac injection of Bevacizumab injection 5 mg/kg and equal dose of concentration 0.9% saline every day of 1 week, respectively. Spectral CT scanning was performed on the 4th and 8th day after treatment, respectively, and CT values at 40-140 keV and iodine content of tumor were measured and compared. At the end of each scanning, 3 rats of each group were randomly selected and sacrificed, and brain tissue were harvested for HE staining and immunohistochemical staining of vascular endothelial growth factor (VEGF). The differences of the amount of VEGF-positive cells at different time points were compared between 2 groups, and the correlations of spectral CT quantitative parameters and the amount of VEGF-positive cells were analyzed. Results Totally 26 rats were included, 13 in experimental group and 13 in control group. There was no statistical difference of CT value of 70 keV single energy nor iodine concentration between 2 groups on day 0 (t=1.35, -0.99, both P>0.05). On the 4th and 8th day after treatment, 70 keV single energy CT value and iodine concentration of experimental group were lower than those of control group (t=-3.56, -6.42 and -6.43, -13.01, all P<0.05). There was no significant difference of the percentage of positive cells between 2 groups on day 0 (P=0.11), while the percentage of positive cells in experimental group (33.93%, 25.00%) on the 4th and 8th day were all lower than those in control group (53.28%, 63.80%, both P<0.05). The 70 keV single energy CT values and iodine concentrations of 2 group were all positively correlated with VEGF at different time points (All P<0.05). Conclusion Energy spectral multi-parameter CT can be used to evaluate the efficacy of Bevacizumab against angiogenesis of C6 glioma rats, which is expected to be a new method for evaluating efficacy of anti-tumor angiogenesis drugs.