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

✍ Scribed by Robert C. Orth; James Bankson; Roger Price; Edward F. Jackson

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 225 KB
• Volume: 58
• Category: Article
• ISSN: 0740-3194
• DOI: 10.1002/mrm.21411

✦ Synopsis

Abstract

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 ≈0.6 kDa), medium (Gadomer‐17, MW~eff~ ≈35 kDa), and high (PG‐Gd‐DTPA, MW ≈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. Magn Reson Med 58:705–716, 2007. © 2007 Wiley‐Liss, Inc.