Tumor microvascular changes in antiangiogenic treatment: Assessment by magnetic resonance contrast media of different molecular weights

Abstract

Purpose:To test magnetic resonance (MR) contrast media of different molecular weights (MWs) for their potential to characterize noninvasively microvascular changes in an experimental tumor treatment model. Materials and Methods:MD-MBA-435, a poorly differentiated human breast cancer cell line, was implanted into 31 female homozygous athymic rats. Animals were assigned randomly to a control (saline) or drug treatment (monoclonal antibody vascular endothelial growth factor (Mab-VEGF) antibody) group. In both groups, dynamic MR imaging (MRI) was performed in each animal using up to three different contrast media on sequential days at baseline and follow-up examination. The MWs of the contrast media used ranged from 557 Da to 92 kDa. Using a bidirectional kinetic model, tumor microvessel characteristics, including the fractional plasma volume (fPV) and transendothelial permeability (K PS ), were estimated for each contrast medium. These microvascular characteristics were compared between drug and control groups and between contrast media of different MWs.Results: Tumors grew significantly slower (P Ͻ 0.0005) in the drug treatment group than in the control group. Mean K PS and fPV values decreased significantly (P Ͻ 0.05) in the Mab-VEGF antibody-treated group compared to baseline values using intermediate or macromolecular contrast media (MMCM), but did not change significantly using small molecular contrast media (SMCM). In the control groups, mean K PS and mean fPV values did not reach statistical significance for any of the contrast media used. Conclusion:Therapeutic effects of a Mab-VEGF antibody on tumor microvessel characteristics can be monitored by dynamic MRI. Intermediate-size agents, such as Gadomer-17, offer a substantial dynamic range and are less limited by imaging precision and therefore should be considered a practical alternative to monitor antiangiogenesis treatment effects in a clinical setting.

Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study

“…CT or MRI modalities have been used in clinical settings to assess tissue perfusion and permeability, particularly with smallmolecule and macromolecular contrast media (18,19). These studies demonstrated that permeability rates depended on molecular or particle properties such as hydrodynamic diameter and shape (4).…”

Increase in tumour permeability following TGF-β type I receptor-inhibitor treatment observed by dynamic contrast-enhanced MRI

“…The choice of the optimal contrast agent is considered to be essential for a successful characterisation of tumour angiogenesis. As macromolecule contrast media show lower permeability than Gd cheleates, it is useful for permeability change monitoring in tumour vasculature (Daldrup-Link et al, 2004;Turetschek et al, 2004); Liposomes are self-closed colloidal particles in which bilayer membranes composed from self-aggregated lipid molecules encapsulate a fraction of the medium. Liposomes have been used as drug carriers for anticancer drugs such as Doxil.…”

T1 measurement of flowing blood and arterial input function determination for quantitative 3D T1‐weighted DCE‐MRI

“…This plasma concentration-time curve, or the arterial input function (AIF), is essential for extracting reliable pharmacokinetic parameters related to tissue physiology such as perfusion, vessel permeability, blood volume, and interstitial volume. These parameters have shown value in brain, myocardial, and tumor applications, perhaps most extensively in the latter, for diagnosis, staging, and therapy monitoring (1). Efforts to improve the quantification of pharmacokinetic parameters and their potential as accurate surrogate markers of hemodynamics have received considerable renewed interest, mainly due to current developments in antivascular, targeted, and other novel therapies.…”