Magnetic resonance molecular imaging of post-stroke neuroinflammation with a P-selectin targeted iron oxide nanoparticle.
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| Abstract |
We 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 approximately 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 T(2) 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%. 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 T(2) 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.
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| Authors | A Y Jin, U I Tuor, D Rushforth, R Filfil, J Kaur, F Ni, B Tomanek, P A Barber |
| Journal | Contrast media & molecular imaging (Contrast Media Mol Imaging) 2009 Nov-Dec Vol. 4 Issue 6 Pg. 305-11 ISSN: 1555-4317 [Electronic] England |
| PMID | 19941323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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