Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model.
OBJECTIVE
To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque.


METHODS
The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis. In vivo magnetic resonance (MR) angiography and T2*-weighted plaque MR imaging were performed at baseline and after administration of P904 and ferumoxtran-10 (administered dose for both, 1000 micromol of iron per kilogram of body weight) in 26 hyperlipidemic New Zealand white rabbits. The variation in vessel wall area over time was evaluated with nonparametric testing. Ex vivo MR imaging findings were compared with iron content at linear regression analysis.


RESULTS
With in vivo MR imaging, plaque analysis was possible as early as 24 hours after P904 injection. The authors observed a 27.75% increase in vessel wall area due to susceptibility artifacts on day 2 (P = .04) and a 38.81% increase on day 3 (P = .04) after P904 administration compared with a 44.5% increase in vessel wall area on day 7 (P = .04) and a 34.8% increase on day 10 (P = .22) after ferumoxtran-10 administration. These susceptibility artifacts were correlated with intraplaque iron uptake in the corresponding histologic slices. The number of pixels with signal loss on the ex vivo MR images was linearly correlated with the logarithm of the iron concentration (P = .0001; R(2) = 0.93).


CONCLUSIONS
Plaque inflammation in rabbits can be detected earlier with P904 than with ferumoxtran-10 owing to the faster blood pharmacokinetics and the early uptake of P904 in the reticuloendothelial system.


BACKGROUND
http://radiology.rsnajnls.org/cgi/content/full/252/2/401/DC1.
Sigovan
Monica
M
Université Lyon 1, CREATIS-LRMN, UMR CNRS 5220, U630 INSERM, ESCPE, La Doua, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France.
Boussel
Loic
L
Sulaiman
Abdulrazzaq
A
Sappey-Marinier
Dominique
D
Alsaid
Hasan
H
Desbleds-Mansard
Catherine
C
Ibarrola
Danielle
D
Gamondès
Delphine
D
Corot
Claire
C
Lancelot
Eric
E
Raynaud
Jean-Sebastian
JS
Vives
Véronique
V
Laclédère
Christine
C
Violas
Xavier
X
Douek
Philippe C
PC
Canet-Soulas
Emmanuelle
E
D000818:Animals; D001025:Aortitis / Q000378:metabolism* / Q000473:pathology*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans; D004195:Disease Models, Animal; D052203:Ferrosoferric Oxide; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D058185:Magnetite Nanoparticles; D008657:Metabolic Clearance Rate; D010087:Oxides / Q000493:pharmacokinetics*; D010865:Pilot Projects; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide