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

Radiology. 2005 Apr;235(1):65-72. doi: 10.1148/radiol.2351040411. Epub 2005 Feb 24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / pharmacokinetics*
  • Gadolinium DTPA / pharmacokinetics*
  • Magnetic Resonance Imaging* / methods
  • Male
  • Mice
  • Mice, Nude
  • Molecular Weight
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / pathology*
  • Neovascularization, Pathologic

Substances

  • Contrast Media
  • Gadolinium DTPA