DCE-MRI-Derived Parameters in Evaluating Abraxane-Induced Early Vascular Response and the Effectiveness of Its Synergistic Interaction with Cisplatin.

Abstract

Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Thirty MDA-MB-435 tumor mice were randomized into three groups: PBS control (C group), Abraxane only (A group), and sequential treatment with Abraxane followed by cisplatin (A-P group). Tumor volume was monitored based on caliper measurements. A DCE-MRI protocol was performed at baseline and day 3. The Ktrans, Kep and Ve were calculated and compared with CD31, α-SMA, and Ki67 histology data. Sequential treatment with Abraxane followed by cisplatin produced a significantly greater inhibition of tumor growth during the three weeks of the observation period. Decreases in Ktrans and Kep for the A and A-P groups were observed on day 3. Immunohistological staining suggested vascular remodeling during the Abraxane therapy. The changes in Ktrans and Kep values were correlated with alterations in the permeability of the tumor vasculature induced by the Abraxane treatment. In conclusion, Abraxane-mediated permeability variations in tumor vasculature can be quantitatively visualized by DCE-MRI, making this a useful method for studying the effects of early cancer treatment, especially the early vascular response. Vascular remodeling by Abraxane improves the efficiency of cisplatin delivery and thus results in a favorable treatment outcome.