Anti-angiogenic therapy affects the relationship between tumor vascular structure and function: a correlation study between micro-CT angiography and DCE-MRI

Abstract

Purpose: To compare the effects of two anti-angiogenic drugs, bevacizumab and a cytosolic phospholipase A2-α inhibitor (AVX235), on the relationship between vascular structure and dynamic contrast enhanced (DCE)-MRI measurements in a patient-derived breast cancer xenograft model. Methods: Mice bearing MAS98.12 tumors were randomized into three groups: bevacizumab-treated (n=9), AVX235-treated (n=9), and control (n=8). DCE-MRI was performed pre-and post-treatment. The median initial area under the concentration-time curve (IAUC60) and volume transfer constant (Ktrans) were computed for each tumor. The tumors were excised for ex vivo micro-CT angiography, from which the vascular surface area (VSA) and fractional blood volume (FBV) were computed. Spearman correlation coefficients (ρ) were computed to evaluate the associations between the DCE-MRI and micro-CT parameters. Results: With the groups pooled, IAUC60 and Ktrans correlated significantly with VSA (ρ=0.475 and 0.527, P=0.019 and 0.008). There were no significant correlations within the control group. There were various significant correlations within the treatment groups but the correlations in the bevacizumab group were of opposite sign, e.g., Ktrans vs. FBV: AVX235 ρ=0.800 (P=0.014), bevacizumab ρ=-0.786 (P=0.023). Conclusion: DCE-MRI measurements can highly depend on vascular structure. The relationship between vascular structure and function changed markedly after antiangiogenic treatment.