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Abstract #4356

Stageing of Atherosclerotic Plaques by a Vascular Cell Adhesion Protein-1 Targeted Contrast Agent

Brigit den Adel1, Carmen Burtea2, Sophie Laurent2, Ernst Suidgeest3, Robert E. Poelmann1, Robert N. Muller2, Louise van der Weerd3, 4

1Anatomy & Embryology, Leiden University Medical Center, Leiden, Netherlands; 2Universit de Mons-Hainaut, Mons, Belgium; 3Radiology, Leiden University Medical Center, Leiden, Netherlands; 4Human Genetics, Leiden University Medical Center, Leiden, Netherlands

We identified a highly specific peptide with nanomolar affinity for human VCAM-1. High resolution MRI performed 1.5 hours after i.v. injection of VCAM-1 targeted USPIOs in aged ApoE-/- mice with advanced plaques showed enhanced uptake of the contrast agent. Young ApoE-/- mice with a collar around the carotid artery, showed an increased uptake of the iron particles, particularly in early plaque stages when VCAM-1 expression is highest. Histology showed co-localisation of VCAM-1 positive endothelial cells and iron deposits in the vessel wall.

Keywords

acquiring activated acute adhesion advanced affinity aged agent agents aims amino anatomy animals aortic arch around arrows artery atherosclerosis ballet binding carotid cell cells chem cine coating collar comparable components conditions conjugated constrictive contrast control corrected covalently cross degree deposits detected determined development diagnosis diet difficult discrimination displayed drives early embryology endothelial enhanced enhancement events exposed expressed expression firm flash gated genetics great highest highly histology hold hours human identified important in vivo induced inflammation inflammatory injection instability intravenous iron kinetics lesions library longitudinal macrophages mediates medical mice model molecular molecule mouse muller muscle negative nevertheless paramagnetic particles particularly passive peptide phage placement plaque plaques port positive post predict probe processes progression promise protein radiology rapidly resolution retrospectively rolling sacrificed scrambled screening secondly sectional several significantly site smooth stages staging still studies successfully synthetic system targeted terminal therapy type typical uptake variant vascular vectorized vertical vessel view views wall weakly weeks western young