Premium
Dual targeted molecular imaging for atherosclerotic plaque detection
Author(s) -
Ferrante Elisa A,
Rychak Joshua J.,
Klibanov Alexander,
Ley Klaus
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.924.22
Subject(s) - selectin , adhesion , chemistry , flow cytometry , sialyl lewis x , biophysics , monoclonal antibody , cell adhesion , microbubbles , biotinylation , streptavidin , p selectin , endothelium , cell adhesion molecule , microbiology and biotechnology , antibody , biochemistry , biotin , immunology , medicine , platelet , biology , ultrasound , platelet activation , organic chemistry , radiology
Selectins and VCAM‐1 are responsible for leukocyte adhesion in atherosclerosis and have been proposed as targets for molecular imaging of the disease. Currently, no method exists to reliably detect inflamed atherosclerotic plaque. In this study, perfluorocarbon‐filled microbubble contrast agents are coupled by a biotin‐streptavidin bridge with mAb MVCAM.A(429), a sialyl Lewis x polymer (sLe x ) or both (dual). Adhesion of these agents respectively to recombinant mouse VCAM‐1 and P‐selectin substrates was investigated in a parallel plate flow chamber at wall shear stresses between 0.5 and 4.5 dyne/cm 2 . The amount of antibody on the bubbles was determined by flow cytometry. The amount of P‐selectin and VCAM‐1 on substrates was determined with 125 I radiolabeled antibodies. Accumulation of both MVCAM.A(429) or sLe x microbubbles was higher on P‐selectin or VCAM‐1 coated substrates rather than casein blocked controls. Both dual targeted and MVCAM.A(429) microbubbles showed increased adhesion over controls. Interactions between SLe x bubbles and the substrate predominantly consisted of rolling rather than adhesion. Dual targeting can increase the binding efficiency of contrast agents to substrates that mimic inflamed endothelium, suggesting they may be useful for atherosclerotic plaque detection. Supported in part by NIH 2 R01 EB002185.