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Dynamic Contrast-enhanced MR Imaging Kinetic Parameters and Molecular Weight of Dendritic Contrast Agents in Tumor Angiogenesis in Mice¹

¹ From the Department of Radiology (Q.G.d.L., R.G.H.B.T., J.M.A.v.E., W.H.B.) and Angiogenesis Laboratory, Departments of Pathology and Internal Medicine (A.W.G.), Maastricht University Hospital, P. Debyelaan 25, 6202 AZ Maastricht, the Netherlands; and Laboratory of Macromolecular and Organic Chemistry (S.L., M.H.P.v.G.) and Department of Biomedical Engineering (M.H.P.v.G., J.M.A.v.E., W.H.B.), Eindhoven University of Technology, Eindhoven, the Netherlands. Received March 2, 2004; revision requested May 13; revision received June 4; accepted July 8. Supported in part by the Cardiovascular Research Institute, Maastricht, the Netherlands. Address correspondence to Q.G.d.L. (e-mail: qdlu@rdia.azm.nl).

PURPOSE: To evaluate the relationship between dynamic contrast agent–enhanced magnetic resonance (MR) imaging–derived kinetic parameters and contrast agents of equal chemical composition and configuration but with different molecular weights in a tumor angiogenesis model.

MATERIALS AND METHODS: This study was approved by the ethical review committee. Maintenance and care of animals was in compliance with guidelines set by the institutional animal care committee. Dynamic contrast-enhanced MR imaging was performed with dendritic contrast agents in 16 mice with tumor xenografts; mice were placed in groups of four for each molecular weight of the contrast agent. The magnitude and spatial distribution of kinetic parameters (transfer coefficient [K^PS] and plasma fraction [f^PV]) were compared with molecular weight of the contrast agent by determining the Spearman correlation coefficient (r) and the quantitative relationship between the endothelial K^PS and molecular weight.

RESULTS: Inverse relationships between molecular weight of contrast agent and K^PS and f^PV of tumor rim (r = –0.8, P < .001 and r = –0.5, P = .04, respectively) and core (r = –0.7, P = .004 and r = –0.6, P = .01, respectively) were observed. The quantitative relationship between K^PS and molecular weight (MW) was K^PS = 0.4/MW^0.44. A decreasing stepwise pattern in f^PV was noted between contrast agents with low (0.7- and 3.0-kDa) molecular weight and those with high (12- and 51-kDa) molecular weight.

CONCLUSION: Macromolecular permeability is best measured with high-molecular-weight contrast agents; endothelial K^PS values measured with low-molecular-weight contrast agents incorporate tissue perfusion and permeability and demonstrate heterogeneous microcirculatory flow.

© RSNA, 2005

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