Journal
CONTRAST MEDIA & MOLECULAR IMAGING
Volume 11, Issue 1, Pages 77-88Publisher
WILEY-HINDAWI
DOI: 10.1002/cmmi.1661
Keywords
macromolecular; DCE-MRI; tumor vessels; multi-modal imaging; microenvironment; vascular function; tumor mapping
Funding
- NSERC [327579-09]
- Canadian Cancer Society [20251]
- CIHR
- Canadian Breast Cancer Foundation
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Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for MRI. HPG-GdF is a 583kDa hyperbranched polyglycerol doubly tagged with Gd and Alexa 647nm dye, making it both MR and histologically visible. In this study we examined the location of HPG-GdF in whole-tumor xenograft sections matched to in vivo DCE-MR images of both HPG-GdF and Gadovist. Despite its large size, we have shown that HPG-GdF extravasates from some tumor vessels and accumulates over time, but does not distribute beyond a few cell diameters from vessels. Fractional plasma volume (fPV) and apparent permeability-surface area product (aPS) parameters were derived from the MR concentration-time curves of HPG-GdF. Non-viable necrotic tumor tissue was excluded from the analysis by applying a novel bolus arrival time (BAT) algorithm to all voxels. aPS derived from HPG-GdF was the only MR parameter to identify a difference in vascular function between HCT116 and HT29 colorectal tumors. This study is the first to relate low and high molecular weight contrast agents with matched whole-tumor histological sections. These detailed comparisons identified tumor regions that appear distinct from each other using the HPG-GdF biomarkers related to perfusion and vessel leakiness, while Gadovist-imaged parameter measures in the same regions were unable to detect variation in vascular function. We have established HPG-GdF as a biocompatible multi-modal high molecular weight contrast agent with application for examining vascular function in both MR and histological modalities. Copyright (c) 2015 John Wiley & Sons, Ltd.
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