Predictability of FTY720 efficacy in experimental autoimmune encephalomyelitis by in vivo macrophage tracking: Clinical implications for ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging

• Published in: Journal of magnetic resonance imaging 2004-07, Vol.20 (1), p.16-24
• Main Authors: Rausch, Martin, Hiestand, Peter, Foster, Carolyn A., Baumann, Diana R., Cannet, Catherine, Rudin, Markus
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Blood-Brain Barrier; Brain - metabolism; Brain - pathology; cell tracking; Contrast Media; Dextrans; EAE; Encephalomyelitis, Autoimmune, Experimental - diagnosis; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Female; Ferrosoferric Oxide; Fingolimod Hydrochloride; FTY720; Heterocyclic Compounds; Immunohistochemistry; Immunosuppressive Agents - therapeutic use; Iron; macrophages; Macrophages - pathology; Magnetic Resonance Imaging; Magnetite Nanoparticles; Organometallic Compounds; Oxides; Propylene Glycols - therapeutic use; Rats; Rats, Inbred Lew; Receptors, G-Protein-Coupled - agonists; Receptors, Lysophospholipid; Recurrence; S1P receptor agonist; Sphingosine
• ISSN: 1053-1807; 1522-2586
• DOI: 10.1002/jmri.20057

Purpose To examine the efficacy of FTY720 as a new agent to reduce inflammatory activity in an animal model of multiple sclerosis (MS) by in vivo macrophage tracking. Material and Methods FTY720 was used for treatment of rats in a model of chronic relapsing experimental autoimmune encephalomyelitis (EAE) at an oral dose of 0.3 mg/kg/day. Magnetic resonance imaging (MRI) based on in vivo tracking of macrophages labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, immunohistological staining (IHC), and neurological readouts was used to study the burden of disease in treated and untreated animals. Results While untreated animals showed severe paralysis of the hind paws, intense accumulation of macrophages in brain tissue, and areas of blood‐brain barrier (BBB) disruption, FTY720‐treated animals displayed no signs of inflammatory activity or neurological impairment. These observations were made for both acute phase and first relapse. Conclusion Tracking of macrophages by MRI provides direct evidence of the immunomodulatory efficacy of FTY720 in the EAE model and correlates well with neurological symptoms and histology. J. Magn. Reson. Imaging 2004;20:16–24. © 2004 Wiley‐Liss, Inc.