Magnetic resonance molecular imaging of post-stroke neuroinflammation with a P-selectin targeted iron oxide nanoparticle.
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.
Jin
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AY
Department of Clinical Neurosciences, the Experimental Imaging Centre, and Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Alberta, Canada.
Tuor
U I
UI
Rushforth
D
D
Filfil
R
R
Kaur
J
J
Ni
F
F
Tomanek
B
B
Barber
P A
PA
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005290:Ferric Compounds / Q000737:chemistry*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D019007:P-Selectin / Q000378:metabolism*
D003287:Contrast Media; D005290:Ferric Compounds; D019007:P-Selectin; C000499:ferric oxide