Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice

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 enclothelial 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/MW0.44. 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; enclothelial K-PS values measured with low-molecular-weight contrast agents incorporate tissue perfusion and permeability and demonstrate heterogeneous microcirculatory flow, (C) RSNA, 2005.