Assessing tumor angiogenesis using macromolecular MR imaging contrast media

J Magn Reson Imaging. Jan-Feb 1997;7(1):68-74. doi: 10.1002/jmri.1880070110.


MRI enhanced with a macromolecular contrast medium (MMCM) has previously been shown to estimate tumor microvascular characteristics that correlate closely with histologic microvascular density, an established surrogate of tumor angiogenesis. A similar MMCM-enhanced MRI technique has now been used to investigate the acute tumor microvascular effects of antibody-mediated inhibition of vascular endothelial growth factor (VEGF), a well-studied and potent angiogenesis stimulator. Athymic rats xenografted with a human breast carcinoma (MDA-MB-435) were imaged after administration of albumin-gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA30) using a heavily T1-weighted three dimensional-spoiled gradient-refocused acquisition in a steady-state pulse sequence before and 24 hours after treatment with anti-VEGF antibody (single dose of 1 mg). Changes in longitudinal relaxivity (delta R1) were analyzed using a bidirectional two-compartment kinetic model to estimate tumor fractional blood volume (fBV) and permeability surface area product (PS). Data showed a significant decrease (P < 0.05) of tumor PS with respect to macromolecular contrast medium at 24 hours after treatment with anti-VEGF antibody. No significant change was observed in fBV. Suppression of tumor microvascular permeability induced by anti-VEGF antibody can be detected and quantified by MMCM-enhanced MRI. MRI grading of tumor angiogenesis and monitoring of anti-angiogenesis interventions could find wide clinical application.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Contrast Media* / pharmacokinetics
  • Diagnosis, Differential
  • Endothelial Growth Factors / analysis*
  • Humans
  • Image Enhancement / methods*
  • Magnetic Resonance Imaging / methods*
  • Neoplasms / blood supply
  • Neoplasms / diagnosis*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / diagnosis*
  • Rats
  • Sensitivity and Specificity


  • Contrast Media
  • Endothelial Growth Factors