Monitoring the therapeutic efficacy of CA4P in the rabbit VX2 liver tumor using dynamic contrast-enhanced MRI

PURPOSE The present work aims to evaluate whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can monitor the blocking effect of combretastatin-A4-phosphate (CA4P) on microvessels and assess the therapeutic efficacy. METHODS Forty rabbits were implanted VX2 tumor specimens. Two weeks later, serial MRI (T1-weighted imaging, T2-weighted imaging, and DCE) were performed at 0 h, 4 h, 24 h, 3 days, and 7 days after CA4P (10 mg/kg) or saline treatment. The parameters of DCE (K-trans, K-ep, V-e and iAUC60) enhancement of tumor portions were measured. Then all tumor samples were stained to count microvessel density (MVD). Finally, two-way repeated measures ANOVA was used to analyze the difference between and within groups. Correlation between the DCE parameters and MVD was analyzed by using the Pearson correlation and Spearman rank correlation. RESULTS K-trans and iAUC60 values at 4 h after CA4P treatment were significantly lower than those in the control group (D-value: -0.133 min(-1), 95%CI: -0.169 to -0.097 min(-1), F= 59.109, p < 0.001 for K-trans; D-value: -10.533 mmol/s, 95%CI: -17.147 to - 3.919 mmol/s, F= 11.110, and p = 0.003 for iAUC60). In the CA4P group, Ktrans and iAUC60 reached the minimum values at 4 h, and both parameters showed significant difference between 4 h and other time points (all p < 0.01). Seven-day values of K-trans (r=0.532, p = 0.016 and r=0.681, p = 0.001, respectively) and iAUC60 (r=0.580, p = 0.007 and r=0.568, p = 0.009, respectively) showed correlation with MVD in both groups, while K-ep and V-e did not show correlation with MVD (p > 0.05). CONCLUSION The blocking effect of microvessels after CA4P treatment can be evaluated by DCE-MRI, and the parameters of quantitative Ktrans and semi- quantitative iAUC60 can assess the change in tumor angiogenesis noninvasively.