[Value of dynamic MRI in monitoring the microenvironmental changes of anti-vascular therapy in a xenograft model].

2020 
Objective: To explore the feasibility of dynamic-enhanced magnetic resonance imaging (DCE-MRI) and blood oxygen level-dependent MRI (BOLD-MRI) in assessing the hemodynamics and tumor aggressiveness during treatment. Methods: The colon cancer xenograft model was established in BALB/C nude mice with HCT116 cell line. Sixteen nude mice were randomly divided into treatment and control groups (aged 6 to 8 weeks, weighted 15 to 18 g, Certificate No. 11400700325797), which were treated with bevacizumab and saline by intraperitoneal injection on the 1st, 4th, 7th, 10th and 13th day. DCE-MRI and BOLD-MRI were performed before and on the 3th, 6th, 9th, 12th, and 15th day after treatment. The vascular maturity and microenvironment hypoxia were confirmed by pathology. Results: The tumor volume of treatment group was significantly smaller than that of control group after 15 days ((712+/-43) vs (1 051+/-112) mm(3),P<0.01).The measurements of K(trans) were (0.135+/-0.005),(0.147+/-0.006),(0.175+/-0.009),(0.161+/-0.006), (0.140+/-0.005),(0.116+/-0.008)/min (F=81.386, P<0.01); K(ep) were (0.788+/-0.030),(0.804+/-0.036),(0.983+/-0.059), (1.105+/-0.091),(0.840+/-0.047),(0.786+/-0.041)/min(F=45.901,P<0.01);Ve were (0.652+/-0.006), (0.559+/-0.026), (0.466+/-0.016), (0.286+/-0.027), (0.363+/-0.020), (0.246+/-0.033) (F=384.290, P<0.01) and R2* values were (24.813+/-0.961), (24.675+/-1.070), (21.425+/-1.371), (17.850+/-0.885), (24.613+/-0.640), (27.013+/-0.734)/s (F=89.323, P<0.01) showed different trends with time in the treatment group, and the differences were statistically significant. The K(trans) values and tumor vessel maturity index (VMI) were higher than baseline values during 3-12 d after treatment. CD31 positive staining rate and VMI had the strongest correlations with K(trans) values (r=0.854 and 0.795), followed by AUC(180) (r=0.750 and 0.808), Ve (r=0.744 and 0.712) and K(ep) values (r=0.729 and 0.758), all P<0.05. R2* value positively correlated with the positive staining rate of HIF-1alpha and fibronectin (r=0.810 and 0.816), all P<0.05. Conclusion: DCE-MRI and BOLD-MRI are adequate to observe the tumor perfusion and hypoxia during anti-vascular treatment, and the R2* value can predict the tumor metastatic potential during the process of vascular normalization.
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