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

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 (K_ep, K_el, and A^H 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). K_ep (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, K_ep (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, K_ep 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

K_ep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.