Biomimetic MRI Contrast Agent for Imaging of Inflammation in Atherosclerotic Plaque of ApoE−/− Mice: A Pilot Study


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Abstract

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.Methods and 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 μmol 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.Conclusion: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.

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