1. Invest Radiol. 2009 Jul;44(7):398-404.

In vivo detection of inflammation using pegylated iron oxide particles targeted
at E-selectin: a multimodal approach using MR imaging and EPR spectroscopy.

Radermacher KA, Beghein N, Boutry S, Laurent S, Vander Elst L, Muller RN, Jordan 
BF, Gallez B.

Biomedical Magnetic Resonance Unit, Louvain Drug Research Institute, Brussels,
Belgium.

OBJECTIVES: 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. MATERIALS
AND 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. 
CONCLUSION: 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.

PMID: 19554667 [PubMed - indexed for MEDLINE]