FeCo/graphite nanocrystals for multi-modality imaging of experimental vascular inflammation.
BACKGROUND
FeCo/graphitic-carbon nanocrystals (FeCo/GC) are biocompatible, high-relaxivity, multi-functional nanoparticles. Macrophages represent important cellular imaging targets for assessing vascular inflammation. We evaluated FeCo/GC for vascular macrophage uptake and imaging in vivo using fluorescence and MRI.


RESULTS
Hyperlipidemic and diabetic mice underwent carotid ligation to produce a macrophage-rich vascular lesion. In situ and ex vivo fluorescence imaging were performed at 48 hours after intravenous injection of FeCo/GC conjugated to Cy5.5 (n = 8, 8 nmol of Cy5.5/mouse). Significant fluorescence signal from FeCo/GC-Cy5.5 was present in the ligated left carotid arteries, but not in the control (non-ligated) right carotid arteries or sham-operated carotid arteries (p = 0.03 for ligated vs. non-ligated). Serial in vivo 3T MRI was performed at 48 and 72 hours after intravenous FeCo/GC (n = 6, 270 µg Fe/mouse). Significant T2* signal loss from FeCo/GC was seen in ligated left carotid arteries, not in non-ligated controls (p = 0.03). Immunofluorescence staining showed colocalization of FeCo/GC and macrophages in ligated carotid arteries.


CONCLUSIONS
FeCo/GC accumulates in vascular macrophages in vivo, allowing fluorescence and MR imaging. This multi-functional high-relaxivity nanoparticle platform provides a promising approach for cellular imaging of vascular inflammation.
Division of Cardiovascular Medicine, Stanford University, Stanford, California, United States of America.
Hisanori
H
Kosuge
Sarah P
SP
Sherlock
Toshiro
T
Kitagawa
Masahiro
M
Terashima
Joëlle K
JK
Barral
Dwight G
DG
Nishimura
Hongjie
H
Dai
Michael V
MV
McConnell
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics*; D002339:Carotid Arteries; D003035:Cobalt; D003287:Contrast Media / Q000737:chemistry; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D005296:Ferrous Compounds; D006108:Graphite / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006949:Hyperlipidemias / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000175:diagnosis / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage
D001672:Biocompatible Materials; D003287:Contrast Media; D005296:Ferrous Compounds; C007717:ferrocobalt; D003035:Cobalt; D006108:Graphite
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