Comparison of single- and dual-tracer pharmacokinetic modeling of dynamic contrast-enhanced MRI data using low, medium, and high molecular weight contrast agents.
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.
Orth
Robert C
RC
Department of Imaging Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. rorth@ucsd.edu
Bankson
James
J
Price
Roger
R
Jackson
Edward F
EF
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007089:Image Enhancement; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D008432:Mathematical Computing; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D008970:Molecular Weight
D003287:Contrast Media; C402765:gadomer 17; D005682:Gadolinium; D019786:Gadolinium DTPA