Evaluation Of The Anti-angiogenic Effect Of Bevacizumab On Rat C6 Glioma By Spectral Computed Tomography

Purposes:To explore the feasibility and value of spectral CT quantitative parameters to evaluate the anti-angiogenic effect of bevacizumab on rat C6 glioma.Methods:Forty healthy male SD rats were selected and C6 glioma cells were implanted in the right basal ganglia of rats to establish the model.On the 14th day after tumor implantation,all rats were scanned by spectral CT,and the tumor formation was observed.As no tumor was found in one rat,and one rat died unexpectedly after the completion of the spectral CT scan,the remaining 38 rats were randomly divided into control group(n=19)and experimental group(n=19).Rats in the control group were given saline(0.2?l/g)and rats in the experimental group(0.2?l/g)at the same time every day for 7 days.Spectral CT scanning was performed on the 4th and 8th day after treatment,and the tumor volume and spectral CT parameters such as 70 keV single energy CT value,slope of energy spectrum curve and iodine concentration at different time points were measured by spectral CT post-processing software.After the end of energy spectrum CT scanning at each time point,3 rats in the two groups were randomly selected for cardiac perfusion and brain sampling.The brain tissues were stained with HE and VEGF,HIF-1?,respectively,the brain tissue structure and cell morphology of the rats were observed,and the positive cell expression of VEGF and HIF-1?were counted,and the correlation between the quantitative parameters of spectral CT and the expression of VEGF and HIF-1?were statistically analyzed.Results:1.Tumor formation was observed on the 14th day after modeling.In the control group,the tumor volume was 83.33±14.65 mm~3,99.82±13.15 mm~3and113.25±20.52 mm~3 on the 0th,4th and 8th day,respectively.In the experimental group,the tumor volume was 84.28±13.52 mm~3,80.80±12.12 mm~3 and 77.25±4.12mm~3on the 0th,4th and 8th day,respectively.2.In the control group,the single energy CT values of 70 keV were 81.35±9.98HU,90.77±9.67 HU and 92.08±7.42 HU on the 0th,4th and 8th day,respectively.The slopes of energy spectrum curves were 1.19±0.31,1.09±0.29 and 1.05±0.21,respectively.The iodine concentrations were 18.21±1.43 mg/cm~3,22.32±5.35 mg/cm~3and 27.12±5.06 mg/cm~3,respectively.In the experimental group,the single energy CT values of 70 keV were 85.97±9.04 HU,80.58±5.57 HU,75.51±5.42 HU on the 0th,4th and 8th day,respectively.The slopes of energy spectrum curves were 1.27±0.43,1.42±0.38,1.54±0.39,respectively.The iodine concentrations were 17.48±2.07mg/cm~3,11.91±3.23 mg/cm~3,9.51±1.36 mg/cm~3,respectively.3.The percentage of VEGF positive cells on the 0th,4th and 8th day in the control group was 46.50%,53.28%and 63.80%respectively,while that in the experimental group on the 0th,4th and 8th day was 45.40%,33.93%and 25%,respectively;The percentage of HIF-1?positive cells in the control group on the 0th,4th and 8th day were 36.53%,52.80%and 68.87%respectively,while that of the experimental group on the 0th,4th and 8th days were 37.47%,25.93%and 17.47%,respectively.4.On the 0th,4th and 8th day in the control group,the correlation coefficient r values between 70 keV single energy CT value and VEGF were 0.737,0.668 and0.609(P<0.05),the correlation coefficient r values between slope of energy spectrum curve and VEGF were 0.610,0.611 and 0.646(P<0.05),and the correlation coefficient r values between iodine concentration and VEGF were 0.563,0.702 and0.558(P<0.05),respectively.On the 0th,4th and 8th day in the experimental group,the correlation coefficient r values between 70 keV single energy CT value and VEGF were 0.737,0.856 and 0.663(P<0.05),the correlation coefficient r values between slope of energy spectrum curve and VEGF were 0.554,0.770 and 0.715(P<0.05),and the correlation coefficient r values between iodine concentration and VEGF were0.555,0.813 and 0.763(P<0.05),respectively.On the 0th,4th and 8th day in the control group,the correlation coefficient r values between 70 keV single energy CT values and HIF-1?were 0.780,0.702,0.616(P<0.05),the correlation coefficient r values between slope of energy spectrum curve and HIF-1?were 0.692,0.631,0.676(P<0.05),and the correlation coefficient r values between iodine concentration and HIF-1?were 0.611,0.685,0.605(P<0.05),respectively.On the 0th,4th and 8th day,the correlation coefficient r values between70 keV single energy CT value and HIF-1?in the experimental group were 0.734,0.851 and 0.767(P<0.05),the correlation coefficient r values between slope of energy spectrum curve and HIF-1?were 0.719,0.763 and 0.792(P<0.05),and the correlation coefficient r values between iodine concentration and HIF-1?were 0.575,0.798 and 0.813(P<0.05),respectively.Conclusion:1.The quantitative parameters of spectral CT,such as single energy CT value of 70 keV,slope of energy spectrum curve and iodine concentration,can evaluate the efficacy of tumor antiangiogenic drugs.2.At different time points,the quantitative parameters of spectral CT,such as single energy CT value of 70 keV,the slope of energy spectrum curve and the concentration of iodine were highly correlated with the expression of VEGF and HIF-1?.Spectral CT is expected to be a new non-invasive and dynamic method to evaluate the efficacy of anti-angiogenic drugs of gliomas.