Detection of vascular cell adhesion molecule‐1 expression with USPIO‐enhanced molecular MRI in a mouse model of cerebral ischemia. (21st November 2012)

• Record Type: Journal Article
• Authors: Fréchou, M.; Beray‐Berthat, V.; Raynaud, J.‐S.; Mériaux, S.; Gombert, F.; Lancelot, E.; Plotkine, M.; Marchand‐Leroux, C.; Ballet, S.; Robert, P.; Louin, G.; Margaill, I.
• Is Part Of: Contrast media & molecular imaging. Volume 8:Number 2(2013:Mar./Apr.)
• Page Start: 157
• Page End: 164
• Publication Date: 2012-11-21
• Subjects: Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1512
• Languages: English
• ISSNs: 1555-4309

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nanoparticular contrast agent P03011, an USPIO (ultrasmall superparamagnetic iron oxide) conjugated to a peptide that targets VCAM‐1 (vascular cell adhesion molecule‐1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM‐1 with MRI after cerebral ischemia in mouse. The time course of VCAM‐1 expression was first examined by immunohistochemistry in our model of cerebral ischemia–reperfusion. Secondly, P03011 or nontargeted USPIO P03007 were injected 5 h after ischemia (100 µmol iron kg<sup>−1</sup>; i.v.) and <italic>in vivo</italic> and <italic>ex vivo</italic> MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM‐1. VCAM‐1 expression was significantly up‐regulated 24 h after ischemia in our model. In animals receiving P03011, both <italic>in vivo</italic> and <italic>ex vivo</italic> MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co‐localization of the targeted USPIO and VCAM‐1. This study demonstrates that VCAM‐1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage. Copyright © 2012 John Wiley & Sons, Ltd.</p> </abstract>