title: VCAM-1-targeted magnetic resonance imaging reveals subclinical disease in a mouse model of multiple sclerosis.
abstract: Diagnosis of multiple sclerosis (MS) currently requires lesion identification by gadolinium (Gd)-enhanced or T(2)-weighted magnetic resonance imaging (MRI). However, these methods only identify late-stage pathology associated with blood-brain barrier breakdown. There is a growing belief that more widespread, but currently undetectable, pathology is present in the MS brain. We have previously demonstrated that an anti-VCAM-1 antibody conjugated to microparticles of iron oxide (VCAM-MPIO) enables in vivo detection of VCAM-1 by MRI. Here, in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we have shown that presymptomatic lesions can be quantified using VCAM-MPIO when they are undetectable by Gd-enhancing MRI. Moreover, in symptomatic animals VCAM-MPIO binding was present in all regions showing Gd-DTPA enhancement and also in areas of no Gd-DTPA enhancement, which were confirmed histologically to be regions of leukocyte infiltration. VCAM-MPIO binding correlated significantly with increasing disability. Negligible MPIO-induced contrast was found in either EAE animals injected with an equivalent nontargeted contrast agent (IgG-MPIO) or in control animals injected with the VCAM-MPIO. These findings describe a highly sensitive molecular imaging tool that may enable detection of currently invisible pathology in MS, thus accelerating diagnosis, guiding treatment, and enabling quantitative disease assessment.
authors: Cancer Research UK/Medical Research Council Gray Institute for Radiation Oncology and Biology, Department of Oncology, Churchill Hospital, Oxford, OX3 7LJ, UK.
authors: Sébastien
authors: S
authors: Serres
authors: Silvy
authors: S
authors: Mardiguian
authors: Sandra J
authors: SJ
authors: Campbell
authors: Martina A
authors: MA
authors: McAteer
authors: Asim
authors: A
authors: Akhtar
authors: Alexandre
authors: A
authors: Krapitchev
authors: Robin P
authors: RP
authors: Choudhury
authors: Daniel C
authors: DC
authors: Anthony
authors: Nicola R
authors: NR
authors: Sibson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis* / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005290:Ferric Compounds; D019786:Gadolinium DTPA; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000378:metabolism*; D057170:Translational Research, Biomedical; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D019010:Vascular Cell Adhesion Molecule-1; C000499:ferric oxide; D019786:Gadolinium DTPA