Early Prediction of Tumor Response to Bevacizumab Treatment in Murine Colon Cancer Models Using Three-Dimensional Dynamic Contrast-Enhanced Ultrasound Imaging

Abstract

To evaluate whether three-dimensional (3D) dynamic contrast-enhanced ultrasound (DCE-US) imaging allows assessing early changes in tumor perfusion following antiangiogenic treatment, and whether these changes could predict treatment response in two animal models of colon cancer that simulate clinical responders and nonresponders. Clinically responding (n=20; LS174T) and nonresponding (n=20; CT26) colon cancer xenografts were established in 40 mice. Ten mice from each group received either antiangiogenic therapy (anti-VEGF blocking with bevacizumab, 10mg/kg) or saline as controls and were imaged longitudinally with 3D DCE-US at baseline (day 0) and days 1, 3, 7, and 10 following treatment. The change in three perfusion parameters (peak enhancement [PE], area under curve [AUC], time to peak [TTP]) relative to baseline was compared to the percentage area of neovasculature on ex vivo quantitative immunofluorescence and with response at day 10 assessed by tumor volume. PE and AUC significantly decreased in LS174T tumors within 1 day after antiangiogenic treatment (P=0.005), but not in CT26 tumors (P>0.05). Similarly, the percentage area of neovasculature on immunofluorescence significantly decreased in treated vs. control LS174T tumors (P<0.001), but not in treated vs. control CT26 tumors (P=0.796). Early decrease in both PE and AUC by 45-50% were predictive of treatment response in 100% (95% CI, 69.2%, 100%) of responding tumors, and in 100% (95% CI, 88.4%, 100%) and 86.7% (95% CI, 69.3%, 96.2%), respectively, of nonresponding tumors. 3D DCE-US provides clinically relevant information on the variability of tumor response to antiangiogenic therapy and could eventually serve as a biomarker for predicting treatment outcomes.