In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide.
Multiple sclerosis is a disease of the central nervous system that is associated with leukocyte recruitment and subsequent inflammation, demyelination and axonal loss. Endothelial vascular cell adhesion molecule-1 (VCAM-1) and its ligand, alpha4beta1 integrin, are key mediators of leukocyte recruitment, and selective inhibitors that bind to the alpha4 subunit of alpha4beta1 substantially reduce clinical relapse in multiple sclerosis. Urgently needed is a molecular imaging technique to accelerate diagnosis, to quantify disease activity and to guide specific therapy. Here we report in vivo detection of VCAM-1 in acute brain inflammation, by magnetic resonance imaging in a mouse model, at a time when pathology is otherwise undetectable. Antibody-conjugated microparticles carrying a large amount of iron oxide provide potent, quantifiable contrast effects that delineate the architecture of activated cerebral blood vessels. Their rapid clearance from blood results in minimal background contrast. This technology is adaptable to monitor the expression of endovascular molecules in vivo in various pathologies.
McAteer
Martina A
MA
Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.
Sibson
Nicola R
NR
von Zur Muhlen
Constantin
C
Schneider
Jurgen E
JE
Lowe
Andrew S
AS
Warrick
Nicholas
N
Channon
Keith M
KM
Anthony
Daniel C
DC
Choudhury
Robin P
RP
D000208:Acute Disease; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004660:Encephalitis / Q000175:diagnosis*; D042783:Endothelial Cells / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008832:Microchemistry / Q000379:methods*; D008845:Microinjections; D053758:Nanoparticles / Q000737:chemistry; D017072:Neostriatum / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000008:administration & dosage / Q000378:metabolism
D005290:Ferric Compounds; D019010:Vascular Cell Adhesion Molecule-1; C000499:ferric oxide