Dynamic gadobutrol-enhanced MRI predicts early response to antivascular but not to antiproliferation therapy in a mouse xenograft model

Abstract

Purpose Dynamic contrast-enhanced magnetic resonance imaging has been described as a method to assess tumor vascularity and, therefore, is discussed as a noninvasive biomarker for drug response prediction in tumor therapies. Because antiangiogenic and antiproliferative drugs are frequently combined for therapy, the aim was to investigate (1) the early response predictability and (2) the extent to which these therapy types influence dynamic contrast-enhanced magnetic resonance imaging with gadobutrol soon after therapy initiation. Methods Mice bearing a KPL-4 tumor were treated with either bevacizumab as an antiangiogenic drug or trastuzumab as a cytotoxic anti-tumor drug. The gadobutrol-contrast agent exposure of the tumor was recorded before and at several time points after therapy initiation to examine the response prediction by dynamic contrast-enhanced magnetic resonance imaging. Results Both therapies resulted in significant tumor growth attenuation over 30 days of therapy, but the individual response to each therapy was different. Specifically, bevacizumab affected the dynamic gadobutrol-enhanced MRI-derived area under the curve at early time points (≤8 days), while trastuzumab did not. Conclusion The area under the curve obtained from dynamic gadobutrol-enhanced MRI predicted early tumor response to the antiangiogenic drug bevacizumab, but not to the anti-tumor cell drug trastuzumab. This indicates that the area under the curve may be useful for assessing early antiangiogenic but not antiproliferative drug effects. © 2013 Wiley Periodicals, Inc.