Abstract 5241: Assessing tumor response to anti-angiogenic therapy with novel DCE-MRI method
Authors: Artemov Dmitri , Kato Yoshinori , Zhu Wenlian , Raman Venu , Bhujwalla Zaver M. 
Published: February 2011

Modulation of the tumor microenvironment by the anti-angiogenic component of combination therapy can result in multiple responses including suppression of aberrant neovascularization in the tumor and normalization of tumor vasculature that may improve delivery of cytotoxic compounds. However, important unresolved questions still exist regarding the role of anti-angiogenic therapy in tumor physiology and progression, particularly regarding its role in the induction or modulation of tumor hypoxia that is an important determinant of tumor aggressiveness.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) can characterize tumor vascular parameters non-invasively and longitudinally. We developed a new MRI technique that provides quantitative measurements of tumor vascular parameters such as vascular volume (VV) and vascular permeability surface area product (PS) and is insensitive to water exchange kinetics between different in vivo compartments.

Changes in tumor vascular parameters were monitored in the course of combination therapy with paclitaxel and bevacizumab in preclinical models of human breast carcinomas MCF-7 and MDA-MB-231. To assess the induction of tumor hypoxia by the therapy a clone of MDA-MB-231 cells engineered to express red fluorescence protein, tdTomato, under hypoxic conditions was used. MR images were acquired pre-, 5 and 10 day post-treatment. Vascular parameters, VV and PS, of the tumors were visualized and quantified using a horizontal bore Bruker Biospec 9.4T MR spectrometer with albumin-GdDTPA blood pool contrast agent. Additionally, top 50-percentile of the VV distribution represents the tumor microangiography map that reveals details of blood vessel morphology within the tumor. Tumor hypoxia was monitored non-invasively using a Xenogen in vivo optical imaging system in the course of the treatment. At the end-point, the tumors were excised, cut into 1 mm slices, and imaged with the Xenogen system. MR data were analyzed using in-house software written in the IDL programming environment. Image registration and 3D renderings were performed using Amira visualization software.

Significant changes in tumor vascular parameters accompanied by increased hypoxia possibly as a result of decreased vascular supply were detected in treated animals. The new DCE-MRI method minimizes effects of water exchange and blood flow on the assessment of tumor microvasculature and provides a reliable determination of vascular parameters both in highly permeable tumor areas with potentially fast water exchange and in mature blood vessels that contain slowly exchangeable water. This method can improve noninvasive detection of the tumor therapeutic response to antiangiogenic treatment.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5241.