Renal vascular inflammation induced by Western diet in ApoE-null mice quantified by (19)F NMR of VCAM-1 targeted nanobeacons.
We have designed multifunctional nanoparticulate reporter bioprobes capable of targeting vascular cell adhesion molecule 1 (VCAM-1), which is up-regulated in numerous inflammatory processes. These perfluorocarbon-cored nanoparticles emit a unique (19)F magnetic resonance (MR) signature, providing the potential to localize and quantify VCAM-1 expression in early atherosclerosis. Nanoparticle-VCAM-1 targeting specificity was confirmed by in vitro binding and competition studies. ApoE-null and control C57-BL6 mice (n = 6/group), fed a Western diet for 35 weeks, were injected i.v. with targeted or non-targeted nanoparticles. After two hours, kidneys were excised and prepared for analysis. ApoE-null kidneys exhibited increased VCAM-1-targeted nanoparticle content over healthy controls by (19)F MR spectroscopy (36.5+8.8 vs. 9.3+2.2 x 10(8)/g, P < .05), which correlated with increased VCAM-1 staining (2.5 +/- 1.3% vs. 0.9 +/- 0.3%, P < .05); their relative biodistributions were confirmed by fluorescence microscopy and MR imaging. These molecular imaging agents offer new approaches for detection, quantification, and longitudinal evaluation of early inflammation utilising (19)F MR spectroscopy and imaging.


BACKGROUND
Multifunctional nanoparticulate reporter bioprobes capable of targeting vascular cell adhesion molecule 1 (VCAM-1) are reported in this paper. These perfluorocarbon-cored nanoparticles offer new approaches for detection, quantification, and longitudinal evaluation of early inflammation utilising 19F MR spectroscopy and imaging.
Southworth
Richard
R
King's College London, The Rayne Institute, St. Thomas' Hospital, UK.
Kaneda
Megan
M
Chen
Junjie
J
Zhang
Lei
L
Zhang
Huiying
H
Yang
Xiaoxia
X
Razavi
Reza
R
Lanza
Gregory
G
Wickline
Samuel A
SA
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D004032:Diet; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008856:Microscopy, Fluorescence; D015336:Molecular Probe Techniques; D053758:Nanoparticles / Q000737:chemistry*; D014018:Tissue Distribution; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1