Dynamic contrast-enhanced MRI (DCE-MRI) is a promising technique for assessing the response of
tumor vasculature to antivascular
therapies. Multiagent DCE-MRI employs a combination of low and high molecular weight
contrast agents, which potentially improves the accuracy of estimation of
tumor hemodynamic and vascular permeability parameters. In this study, we used multiagent DCE-MRI to assess changes in
tumor hemodynamics and vascular permeability after vascular-disrupting
therapy. Multiagent DCE-MRI (sequential injection of G5
dendrimer, G2
dendrimer, and
Gd-DOTA) was performed in
tumor-bearing mice before, 2 and 24 hours
after treatment with vascular disrupting agent
DMXAA or placebo. Constrained DCE-MRI gamma capillary transit time modeling was used to estimate flow F, blood volume fraction vb, mean capillary transit time tc, bolus arrival time td, extracellular extravascular fraction ve, vascular heterogeneity index α-1 (all identical between agents) and extraction fraction E (reflective of permeability), and transfer constant Ktrans (both agent-specific) in perfused pixels. F, vb, and α-1 decreased at both time points after
DMXAA, whereas tc increased. E (G2 and G5) showed an initial increase, after which, both parameters restored. Ktrans (G2 and
Gd-DOTA) decreased at both time points
after treatment. In the control, placebo-treated animals, only F, tc, and Ktrans
Gd-DOTA showed significant changes. Histologic perfused
tumor fraction was significantly lower in
DMXAA-treated versus control animals. Our results show how multiagent tracer-kinetic modeling can accurately determine the effects of vascular-disrupting
therapy by separating simultaneous changes in
tumor hemodynamics and vascular permeability.Significance: These findings describe a new approach to measure separately the effects of antivascular
therapy on
tumor hemodynamics and vascular permeability, which could help more rapidly and accurately assess the efficacy of
experimental therapy of this class.
Cancer Res; 78(6); 1561-70. ©2018 AACR.