Monitoring the effects of dexamethasone treatment by MRI using in vivo iron oxide nanoparticle-labeled macrophages

Azza Gramoun , Lindsey Crowe (1) , Lionel Maurizi (2) , Wolfgang Wirth , Frank Tobalem , Kerstin Grosdemange , Geraldine Coullerez , Felix Eckstein , Marije Koenders (3) , Wim van den Berg (4) , Heinrich Hofmann (5) , Jean-Paul Vallée (1)

1 HUG - Geneva University Hospital
2 ICB - Laboratoire Interdisciplinaire Carnot de Bourgogne
3 Radboud University Medical Center [Nijmegen]
4 Rheumatology Research & Advanced Therapeutics
5 Powder Technology Laboratory

Introduction: Rheumatoid arthritis (RA) is a chronic disease causing recurring inflammatory joint attacks. These attacks are characterized by macrophage infiltration contributing to joint destruction. Studies have shown that RA treatment efficacy is correlated to synovial macrophage number. The aim of this study was to experimentally validate the use of in vivo superparamagnetic iron oxide nanoparticle (SPION) labeled macrophages to evaluate RA treatment by MRI. Methods: The evolution of macrophages was monitored with and without dexamethasone (Dexa) treatment in rats. Two doses of 3 and 1 mg/kg Dexa were administered two and five days following induction of antigen induced arthritis. SPIONs (7 mg Fe/rat) were injected intravenously and the knees were imaged in vivo on days 6, 10 and 13. The MR images were scored for three parameters: SPION signal intensity, SPION distribution pattern and synovial oedema. Using 3D semi-automated software, the MR SPION signal was quantified. The efficacy of SPIONs and gadolinium chelate (Gd), an MR contrast agent, in illustrating treatment effects were compared. Those results were confirmed through histological measurements of number and area of macrophages and nanoparticle clusters using CD68 immunostaining and Prussian blue staining respectively.

Domaines: Micro et nanotechnologies/Microélectronique

Azza Gramoun, Lindsey Crowe, Lionel Maurizi, Wolfgang Wirth, Frank Tobalem, et al.. Monitoring the effects of dexamethasone treatment by MRI using in vivo iron oxide nanoparticle-labeled macrophages. Arthritis Research and Therapy, 2014, 16 (3), pp.R131. ⟨10.1186/ar4588⟩. ⟨hal-02163410⟩