PMID- 21908714 OWN - NLM STAT- MEDLINE DCOM- 20120228 LR - 20230608 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 25 IP - 12 DP - 2011 Dec TI - VCAM-1-targeted magnetic resonance imaging reveals subclinical disease in a mouse model of multiple sclerosis. PG - 4415-22 LID - 10.1096/fj.11-183772 [doi] AB - 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. FAU - Serres, Sebastien AU - Serres S AD - Cancer Research UK/Medical Research Council Gray Institute for Radiation Oncology and Biology, Department of Oncology, Churchill Hospital, Oxford, OX3 7LJ, UK. FAU - Mardiguian, Silvy AU - Mardiguian S FAU - Campbell, Sandra J AU - Campbell SJ FAU - McAteer, Martina A AU - McAteer MA FAU - Akhtar, Asim AU - Akhtar A FAU - Krapitchev, Alexandre AU - Krapitchev A FAU - Choudhury, Robin P AU - Choudhury RP FAU - Anthony, Daniel C AU - Anthony DC FAU - Sibson, Nicola R AU - Sibson NR LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - 088291/WT_/Wellcome Trust/United Kingdom GR - 090532/WT_/Wellcome Trust/United Kingdom GR - G0401438/MRC_/Medical Research Council/United Kingdom PT - Comparative Study PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110909 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Contrast Media) RN - 0 (Ferric Compounds) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 1K09F3G675 (ferric oxide) RN - K2I13DR72L (Gadolinium DTPA) SB - IM MH - Animals MH - Brain/metabolism/pathology MH - Contrast Media MH - Disease Models, Animal MH - Disease Progression MH - Encephalomyelitis, Autoimmune, Experimental/*diagnosis/*metabolism MH - Endothelium/metabolism/pathology MH - Female MH - Ferric Compounds MH - Gadolinium DTPA MH - Humans MH - Immunohistochemistry MH - Magnetic Resonance Imaging/*methods MH - Mice MH - Multiple Sclerosis/*diagnosis/*metabolism MH - Translational Research, Biomedical MH - Vascular Cell Adhesion Molecule-1/*metabolism PMC - PMC3394669 MID - UKMS47719 OID - NLM: UKMS47719 EDAT- 2011/09/13 06:00 MHDA- 2012/03/01 06:00 PMCR- 2012/07/11 CRDT- 2011/09/13 06:00 PHST- 2011/09/13 06:00 [entrez] PHST- 2011/09/13 06:00 [pubmed] PHST- 2012/03/01 06:00 [medline] PHST- 2012/07/11 00:00 [pmc-release] AID - fj.11-183772 [pii] AID - 10.1096/fj.11-183772 [doi] PST - ppublish SO - FASEB J. 2011 Dec;25(12):4415-22. doi: 10.1096/fj.11-183772. Epub 2011 Sep 9.