A comparative study of dynamic contrast-enhanced MRI parameters as biomarkers for anti-angiogenic drug therapy

Abstract

The aim of the present study was to compare three tracer kinetics methods for the analysis of dynamic contrast-enhanced (DCE) MRI data, namely the generalized kinetics model, the distributed-parameter model and the initial area under the tumor tracer curve (IAUC) method, in a Phase I study of an anti-angiogenic drug ABT -869; and to explore their utility as biomarkers. Twenty-eight patients with a range of tumors formed the study population. DCE MRI performed at baseline and 2 weeks post-treatment was analyzed using all three methods, yielding percentage changes for various tracer kinetics parameters. Correlation analyzes were performed between these parameters and in relation to drug exposure. The association of these parameters with time-to-progression was examined using receiver-operating characteristic and Kaplan-Meier curves. Significant correlation with drug exposure was found for the following parameters: normalized IAUC (IAUC norm), fractional interstitial volume v e, fractional intravascular volume v 1 and permeability PS. However, only v e and PS were effective in predicting late progression. A decrease in v e of more than 1.7% and a decrease in PS of more than 25.1% observed at 2 weeks post-treatment could be associated with late progression. All three tracer kinetics methods have biomarker potential for assessing the effects of anti-angiogenic therapy. Copyright © 2011 John Wiley & Sons, Ltd. Dynamic contrast-enhanced (DCE) MRI parameters derived from three tracer kinetics methods were compared in a Phase I trial of an anti-angiogenic drug ABT-869, by correlating the parameters to drug exposure and patient outcome. Results show that certain DCE MRI parameters which correlated with drug exposure and are predictive of tumor progression, can potentially serve as biomarkers in anti-angiogenic drug trials. © 2011 John Wiley & Sons, Ltd.