Magnetic resonance molecular imaging of post-stroke neuroinflammation with a P-selectin targeted iron oxide nanoparticle

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DOIResolve DOI: http://doi.org/10.1002/cmmi.292
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TypeArticle
Journal titleContrast Media & Molecular Imaging
Volume4
Issue6
Pages305311; # of pages: 7
Subjectmagnetic resonance imaging; P-selectin; stroke; neuroinflammation; iron oxide; nanoparticle
AbstractWe have developed a magnetic resonance molecular imaging method using a novel iron-oxide contrast agent targeted towards P-selectin – MNP-PBP (magnetic nanoparticle-P-selectin binding peptide) – to image endothelial activation following cerebral ischemia/reperfusion. MNP-PBP consists of ∼1000 PBP ligands (primary sequence: GSIQPRPQIHNDGDFEEIPEEYLQ GGSSLVSVLDLEPLDAAWL) conjugated to a 50 nm diameter aminated dextran iron oxide particle. In vitro P- and E-selectin binding was assessed by competition ELISA. Transient focal cerebral ischemia was induced in male C57/BL 6 mice followed by contrast injection (MNP-PBP; MNP-NH2; Feridex; MNP-PBP-FITC) at 24 h after reperfusion and T2 magnetic resonance imaging at 9.4 T was performed. Infarction and microvasculature accumulation of contrast agent was assessed in coronal brain sections. MNP-PBP attenuated antibody binding to P-selectin by 34.8 ± 1.7 percent. P-selectin was preferentially increased in the infarct hemisphere and MNP-PBP-FITC accumulation in the infarct hemisphere microvasculature was observed. Compared with the nontargeted iron oxide agents MNP-NH2 and Feridex, MNP-PBP showed a significantly greater T2 effect within the infarction. MR imaging of P-selectin expression with a targeted iron oxide nanoparticle contrast agent may reveal early endothelial activation in stroke and other neuroinflammatory states.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biodiagnostics; NRC Biotechnology Research Institute; National Research Council Canada
Peer reviewedYes
NPARC number20109990
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Record identifier3a9f9443-8260-43ea-ba5d-e62bb4ea6c5f
Record created2012-06-09
Record modified2016-05-09
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