In vivo detection of inflammation using pegylated iron oxide particles targeted at E-selectin: a multimodal approach using MR imaging and EPR spectroscopy.
OBJECTIVE
Ultrasmall particles of iron oxide (USPIO) possess superparamagnetic properties and are used as negative contrast agent in magnetic resonance imaging (MRI) because of their strong T(2) and T(2)* effects. Besides this method, electron paramagnetic resonance (EPR) offers the unique capability to quantify these particles. The objective of this study was to evaluate a molecular marker for non invasive diagnosis and monitoring of inflammation. During inflammation cell adhesion molecules such as E-selectin are expressed on the endothelial cell surface. An E-selectin ligand was coupled to pegylated USPIO particles.


METHODS
Inflammation was induced by intramuscular injection of Freund's Complete Adjuvant in male NMRI mice. After intravenous injection of grafted or ungrafted USPIO particles, iron concentration in inflamed muscles was quantified ex vivo by X-band EPR. Particle accumulation was also assessed in vivo by L-Band EPR, as well as by T(2)-weighted MRI.


RESULTS
We determined the mean iron oxide concentration in inflamed muscles after injection of grafted or ungrafted UPSIO particles, which was 0.8% and 0.4% of the initially injected dose, respectively. By L-band EPR, we observed that the concentration of the grafted USPIO particles in inflamed muscles was twice higher than for the ungrafted particles. Using MRI experiments, a higher signal loss was clearly observed in the inflamed muscle when grafted particles were injected in comparison with the ungrafted particles.


CONCLUSIONS
Even taking into account a non specific accumulation of iron oxides, the targeting of USPIO particles with E-selectin ligands significantly improved the sensitivity of detection of inflamed tissues.
Radermacher
Kim A
KA
Biomedical Magnetic Resonance Unit, Louvain Drug Research Institute, Brussels, Belgium.
Beghein
Nelson
N
Boutry
Sebastien
S
Laurent
Sophie
S
Vander Elst
Luce
L
Muller
Robert N
RN
Jordan
Benedicte F
BF
Gallez
Bernard
B
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003287:Contrast Media; D003911:Dextrans; D016503:Drug Delivery Systems / Q000379:methods*; D019040:E-Selectin / Q000032:analysis*; D052203:Ferrosoferric Oxide; D007249:Inflammation / Q000175:diagnosis* / Q000378:metabolism*; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D010087:Oxides; D011092:Polyethylene Glycols / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015415:Biomarkers; D003287:Contrast Media; D003911:Dextrans; D019040:E-Selectin; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D011092:Polyethylene Glycols; D007501:Iron; D052203:Ferrosoferric Oxide