Authors: A Broisat L M Riou V Ardisson D Boturyn P Dumy D Fagret C Ghezzi
Publish Date: 2007/01/12
Volume: 34, Issue: 6, Pages: 830-840
Abstract
VCAM1 plays a major role in the chronic inflammatory processes present in vulnerable atherosclerotic plaques The residues 75–84 B2702p and 84–75/75–84 B2702rp of the major histocompatibility complex1 MHC1 molecule B2702 were previously shown to bind specifically to VCAM1 We hypothesised that radiolabelled B2702p and B2702rp might have potential for the molecular imaging of vascular cell adhesion molecule1 VCAM1 expression in atherosclerotic plaquesPreliminary biodistribution studies indicated that 125IB2702rp was unsuitable for in vivo imaging owing to extremely high lung uptake 123I or 99mTclabelled B2702p was injected intravenously to Watanabe heritable hyperlipidaemic rabbits WHHL n = 6 and control animals n = 6 After 180 min aortas were harvested for ex vivo autoradiographic imaging gammawell counting VCAM1 immunohistology and Sudan IV lipid stainingRobust VCAM1 immunostaining was observed in Sudan IVpositive and to a lesser extent in Sudan IVnegative areas of WHHL animals whereas no expression was detected in control animals Significant 29fold and 19fold increases in 123IB2702p and 99mTcB2702p aortictoblood ratios respectively were observed between WHHL and control animals p 005 Tracer uptake on ex vivo images colocalised with atherosclerotic plaques Image quantification indicated a graded increase in 123IB2702p and 99mTcB2702p activities from control to Sudan IVnegative and to Sudan IVpositive areas consistent with the observed pattern of VCAM1 expression Sudan IVpositive to control area tracer activity ratios were 170 ± 90 and 59 ± 18 for 123IB2702p and 99mTcB2702p respectivelyFinancial support was provided by the National Institute for Health and Medical Research INSERM and the French Ministry of National Education and Research All the experimental protocols described in the present study were approved by the Animal Care and Use Committee of the Centre de Recherche et Service de Santé des Armées CRSSA and the experiments were performed by an authorised individual A Broisat authorisation 38 04 37
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