High-affinity alphavbeta3 integrin targeted optical probe as a new imaging biomarker for early atherosclerosis: initial studies in Watanabe rabbits.
OBJECTIVE
A newly developed synthetic alpha v beta 3 integrin targeted optical probe (ITOP) has been demonstrated to target cancer cells, in vivo. Compared to the commercially available cyclic peptide c[RGDfv], this optical probe has at least 20 times better binding affinity for the alpha v beta 3 receptor. The present in vitro study was designed to investigate the possibility of detecting early atherosclerotic plaque by using this ITOP.


METHODS
Experiments were performed on five Watanabe heritable hyperlipidemic rabbits and two New Zealand White rabbits for control. Our ITOP was used for detecting the presence of alpha v beta 3 receptors in vitro.


RESULTS
Segments of plaque accumulation from two distinct regions of ascending and descending aortas were labeled in Watanabe rabbits. The signal was found principally in the adventitia and proximal intima of the aortic vessel, corresponding directly to the expression of integrin alpha v beta 3 as determined by antibody assay. Moreover, there was a close association between the level of labeling with the alpha v beta 3 targeted probe and the thickness of the adventitia.


CONCLUSIONS
This high-affinity ITOP identifies the site and extent of alpha v beta 3 expression and correlates with adventitial thickness. Recent evidence associates alpha v beta 3 expression with the inflammatory process in early vulnerable plaque, making this compound a promising potential biomarker for early atherosclerotic disease.
Heroux
Julie
J
Laboratory of Integrative Cardiovascular Imaging Science, National Institute of Diabetes Digestive and Kidney Diseases, Bethesda, MD 20892, USA. herouxj@nhlbi.nih.gov
Gharib
Ahmed M
AM
Danthi
Narasimhan S
NS
Cecchini
Sylvain
S
Ohayon
Jacques
J
Pettigrew
Roderic I
RI
D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis*; D015415:Biomarkers / Q000378:metabolism; D003238:Connective Tissue / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D042241:Early Diagnosis; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D015335:Molecular Probes; D055620:Optical Phenomena; D011817:Rabbits; D013194:Staining and Labeling
D015415:Biomarkers; D039302:Integrin alphaVbeta3; D015335:Molecular Probes