Document Detail

Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia.
MedLine Citation:
PMID:  23281288     Owner:  NLM     Status:  In-Data-Review    
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(-1) ; i.v.) and in vivo and ex vivo 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 in vivo and ex vivo 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.
M Fréchou; V Beray-Berthat; J-S Raynaud; S Mériaux; F Gombert; E Lancelot; M Plotkine; C Marchand-Leroux; S Ballet; P Robert; G Louin; I Margaill
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Contrast media & molecular imaging     Volume:  8     ISSN:  1555-4317     ISO Abbreviation:  Contrast Media Mol Imaging     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101286760     Medline TA:  Contrast Media Mol Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  157-64     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
Equipe de recherche 'Pharmacologie de la Circulation Cérébrale' EA 4475, Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, 75006, Paris, France; Guerbet, Division Recherche - Service Imagerie Expérimentale, 95943, Roissy, CDG, France.
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