Comparison of single- and dual-tracer pharmacokinetic modeling of dynamic contrast-enhanced MRI data using low, medium, and high molecular weight contrast agents

Magn Reson Med. 2007 Oct;58(4):705-16. doi: 10.1002/mrm.21411.


Pharmacokinetic parameters corresponding to perfused microvascular volume determined from dynamic contrast-enhanced (DCE) MRI data were compared to immunohistochemical measures of microvascular density (MVD) and perfused microvascular density. DCE MRI data from human mammary tumors (MDA-MB-435) implanted in nude mice using low (Gd-DTPA, MW approximately equal 0.6 kDa), medium (Gadomer-17, MW(eff) approximately equal 35 kDa), and high (PG-Gd-DTPA, MW approximately equal 220 kDa) molecular weight contrast agents were analyzed with single- and dual-tracer pharmacokinetic models. MVD values were determined by two manual counting methods, "hot spot" and summed region of interest (SROI). Pharmacokinetic parameters determined using the single-tracer model (Gd-DTPA [n = 15] and Gadomer-17 [n = 13]) did not correlate with MVD measures using either manual counting method. For dual-tracer studies (Gadomer-17/Gd-DTPA [n = 15] and PG-Gd-DTPA/Gd-DTPA [n = 13]), pharmacokinetic parameters demonstrated a statistically significant correlation with MVD determined by the SROI method, but not the "hot spot" method. Ten mice successfully underwent intravital FITC-labeled lectin perfusion with the hemisphere of highest lectin labeling correlating with pharmacokinetic parameter values in 9 of 10 tumors (single-tracer Gd-DTPA [n = 2], single-tracer Gadomer-17 [n = 3], and dual-tracer Gadomer-17/Gd-DTPA [n = 5]). This study demonstrates that dual-tracer DCE MRI studies yield pharmacokinetic parameters that correlate with immunohistochemical measures of MVD.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Contrast Media / pharmacokinetics*
  • Female
  • Gadolinium / pharmacokinetics
  • Gadolinium DTPA / pharmacokinetics
  • Image Enhancement
  • Immunohistochemistry
  • Magnetic Resonance Imaging / methods*
  • Mammary Neoplasms, Experimental / metabolism
  • Mathematical Computing
  • Mice
  • Mice, Nude
  • Models, Biological
  • Molecular Weight


  • Contrast Media
  • gadomer 17
  • Gadolinium
  • Gadolinium DTPA