Dynamic contrast-enhanced MRI for monitoring antiangiogenic treatment: determination of accurate and reliable perfusion parameters in a longitudinal study of a mouse xenograft model

Korean J Radiol. 2013 Jul-Aug;14(4):589-96. doi: 10.3348/kjr.2013.14.4.589. Epub 2013 Jul 17.

Abstract

Objective: To determine the reliable perfusion parameters in dynamic contrast-enhanced MRI (DCE-MRI) for the monitoring antiangiogenic treatment in mice.

Materials and methods: Mice, with U-118 MG tumor, were treated with either saline (n = 3) or antiangiogenic agent (sunitinib, n = 8). Before (day 0) and after (days 2, 8, 15, 25) treatment, DCE examinations using correlations of perfusion parameters (Kep, Kel, and A(H) from two compartment model; time to peak, initial slope and % enhancement from time-intensity curve analysis) were evaluated.

Results: Tumor growth rate was found to be 129% ± 28 in control group, -33% ± 11 in four mice with sunitinib-treatment (tumor regression) and 47% ± 15 in four with sunitinib-treatment (growth retardation). Kep (r = 0.80) and initial slope (r = 0.84) showed strong positive correlation to the initial tumor volume (p < 0.05). In control mice, tumor regression group and growth retardation group animals, Kep (r : 0.75, 0.78, 0.81, 0.69) and initial slope (r : 0.79, 0.65, 0.67, 0.84) showed significant correlation with tumor volume (p < 0.01). In four mice with tumor re-growth, Kep and initial slope increased 20% or greater at earlier (n = 2) than or same periods (n = 2) to when the tumor started to re-grow with 20% or greater growth rate.

Conclusion: Kep and initial slope may a reliable parameters for monitoring the response of antiangiogenic treatment.

Keywords: Angiogenesis; Dynamic contrast enhanced MR; Tumor perfusion; Two compartment model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Contrast Media*
  • Female
  • Heterografts
  • Indoles / therapeutic use*
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neoplasms, Experimental / diagnosis*
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Pyrroles / therapeutic use*
  • Reproducibility of Results
  • Sunitinib
  • Tumor Burden

Substances

  • Angiogenesis Inhibitors
  • Contrast Media
  • Indoles
  • Pyrroles
  • Sunitinib