Dynamic Contrast-Enhanced MRI for Monitoring Antiangiogenic Treatment: Determination of Accurate and Reliable Perfusion Parameters in a Longitudinal Study of a Mouse Xenograft Model

ABSTRACT

OBJECTIVE: To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice. MATERIALS AND METHODS: Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (Kep, Kel, and AH from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated. RESULTS: Tumor growth rate was found to be 129% +/- 28 in control group, -33% +/- 11 in four mice with sunitinib-treatment (tumor regression) and 47% +/- 15 in four with sunitinib-treatment (growth retardation). Kep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, Kep (r 0.75, 0.78, 0.81, 0.69) and initial slope (r 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, Kep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate. CONCLUSION: Kep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.