title: Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model.
abstract: 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.
authors.affiliation: Université Lyon 1, CREATIS-LRMN, UMR CNRS 5220, U630 INSERM, ESCPE, La Doua, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex, France.
authors.forename: Monica
authors.initials: M
authors.lastname: Sigovan
authors.forename: Loic
authors.initials: L
authors.lastname: Boussel
authors.forename: Abdulrazzaq
authors.initials: A
authors.lastname: Sulaiman
authors.forename: Dominique
authors.initials: D
authors.lastname: Sappey-Marinier
authors.forename: Hasan
authors.initials: H
authors.lastname: Alsaid
authors.forename: Catherine
authors.initials: C
authors.lastname: Desbleds-Mansard
authors.forename: Danielle
authors.initials: D
authors.lastname: Ibarrola
authors.forename: Delphine
authors.initials: D
authors.lastname: Gamondès
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
authors.forename: Eric
authors.initials: E
authors.lastname: Lancelot
authors.forename: Jean-Sebastian
authors.initials: JS
authors.lastname: Raynaud
authors.forename: Véronique
authors.initials: V
authors.lastname: Vives
authors.forename: Christine
authors.initials: C
authors.lastname: Laclédère
authors.forename: Xavier
authors.initials: X
authors.lastname: Violas
authors.forename: Philippe C
authors.initials: PC
authors.lastname: Douek
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Canet-Soulas
mesh_terms: 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
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide