MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation.
OBJECTIVE
To define the diagnostic potential of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) particles for the quantitative characterization of tumor microvasculature.


METHODS
NC100150 injection, a USPIO in clinical trials, and albumin-(Gd-DTPA)(30) were compared at MR imaging on sequential days in the same 19 rats with mammary tumors. Kinetic analysis of dynamic T1-weighted three-dimensional spoiled gradient-recalled imaging data with a two-compartment bidirectional model yielded MR imaging estimates of microvascular permeability (K(PS)) and fractional plasma volume (fPV) for each contrast medium.


RESULTS
Strongly positive and significant correlations were observed between MR imaging-derived K(PS )estimates and histologic tumor grade with either the soluble albumin-(Gd-DTPA)(30) (r = 0.88; P <.001) or larger particulate USPIO (r = 0.82; P <.001). A significant correlation (P <.05) was observed with each contrast medium between K(PS) and the histologic microvascular density (MVD), an angiogenesis indicator. Despite the considerable difference in molecule and particle sizes, no significant difference was observed in the MR imaging-derived mean permeability values generated with the two contrast media.


CONCLUSIONS
USPIO, a macromolecular particulate MR imaging contrast agent, can be applied successfully to characterize tumor microvessels in animals. USPIO-derived K(PS) correlated strongly with histopathologic tumor grade, MVD, and K(PS) values derived by using albumin-(Gd-DTPA)(30) in the same tumors.
Turetschek
K
K
Center for Pharmaceutical and Molecular Imaging, Department of Radiology, University of California, San Francisco, Box 0628, 505 Parnassus Ave, San Francisco, CA 94143-0628, USA.
Huber
S
S
Floyd
E
E
Helbich
T
T
Roberts
T P
TP
Shames
D M
DM
Tarlo
K S
KS
Wendland
M F
MF
Brasch
R C
RC
D000818:Animals; D003287:Contrast Media; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D019786:Gadolinium DTPA; D021621:Imaging, Three-Dimensional; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology*; D008833:Microcirculation / Q000473:pathology; D010087:Oxides; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide