Biomimetic MRI contrast agent for imaging of inflammation in atherosclerotic plaque of ApoE-/- mice: a pilot study.
OBJECTIVE
Atherosclerosis involves an inflammatory process characterized by cellular and molecular responses. A slow-clearance blood-pool paramagnetic agent (CMD-A2-Gd-DOTA: P717) chemically modified to create a functionalized product (F-P717) for targeting inflammation in vessel walls was evaluated in vivo in mice.


RESULTS
Carboxylate and sulfate groups were grafted onto the macromolecular paramagnetic Gd-DOTA-dextran backbone. Products were also fluorescently labeled with rhodamine isothiocyanate. Pre- and postcontrast MRI was performed on a 2-Tesla magnet in ApoE-/- and control C57BL/6 mice after P717 or F-P717 injection at a dose of 60 micromol Gd/kg. Axial T1-weighted images of the abdominal aorta were obtained using a 2D multislice spin-echo sequence. F-P717 significantly enhanced the magnetic resonance imaging (MRI) signal in the abdominal aortic wall of ApoE-/- mice (>50% signal-to-noise ratio increase between 10 and 30 minutes), but not of control mice. P717 produced only moderate (<20%) MRI signal enhancement within the same time frame. The MRI data were correlated to histopathology. Immunofluorescence in ApoE-/- mice colocalized F-P717 but not P717 with the inflammatory area revealed by P-selectin labeling.


CONCLUSIONS
This study demonstrates the efficacy of F-P717 as a new molecular imaging agent for noninvasive in vivo MRI location of inflammatory vascular tree lesions in ApoE-/- mice.
Alsaid
Hasan
H
Université de Lyon, Lyon, F-69000, Université Lyon 1, Villeurbanne, F-69622, France.
De Souza
Geneviève
G
Bourdillon
Marie-Claude
MC
Chaubet
Frédéric
F
Sulaiman
Abdulrazzaq
A
Desbleds-Mansard
Catherine
C
Chaabane
Linda
L
Zahir
Charaf
C
Lancelot
Eric
E
Rousseaux
Olivier
O
Corot
Claire
C
Douek
Philippe
P
Briguet
André
A
Letourneur
Didier
D
Canet-Soulas
Emmanuelle
E
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology*; D040761:Biomimetic Materials; D003287:Contrast Media; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010865:Pilot Projects; D014657:Vasculitis / Q000473:pathology*
D001057:Apolipoproteins E; D003287:Contrast Media