INTRODUCTION: The detection of @entity731 at risk for disruption will be greatly enhanced by molecular probes that target vessel wall biomarkers. Here, we test if fluorescently-labeled Activatable Cell Penetrating Peptides (ACPPs) could differentiate stable plaques from vulnerable plaques that disrupt, forming a luminal @entity715 . Additionally, we test the efficacy of a combined @entity68843 and MRI technique for identifying plaques at high risk of @entity397 . METHODS AND RESULTS: In an atherothrombotic @entity95 model, disrupted plaques were identified with in vivo MRI and co-registered in the same @entity95 aorta with the in vivo uptake of ACPPs, cleaved by matrix metalloproteinases (MMPs) or @entity11328 . @entity68843 uptake, mapped ex vivo in whole aortas, was higher in disrupted compared to non-disrupted plaques. Specifically, disrupted plaques demonstrated a 4.5~5.0 fold increase in fluorescence enhancement, while non-disrupted plaques showed only a 2.2~2.5 fold signal increase. Receiver operating characteristic (ROC) analysis indicates that both ACPPs (MMP and @entity11328 ) show high specificity (84.2% and 83.2%) and sensitivity (80.0% and 85.7%) in detecting disrupted plaques. The detection power of ACPPs was improved when combined with the MRI derived measure, outward remodeling ratio. CONCLUSIONS: Our targeted fluorescence @entity68843 probes distinguished disrupted plaques from stable plaques with high sensitivity and specificity. The combination of anatomic, MRI-derived predictors for disruption and @entity68843 uptake can further improve the power for identification of high-risk plaques and suggests future development of ACPPs with molecular MRI as a readout.

Identification of High-Risk Plaques by MRI and Fluorescence Imaging in a XXXX Model of Atherothrombosis.

@entity11328 :: ('100009146(Tax:9986)', 'Gene') :: ['thrombin'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity68843 :: ('100352974(Tax:9986)', 'Gene') :: ['ACPP'] @entity397 :: ('MESH:D012421', 'Disease') :: ['rupture'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerotic plaques'] @entity715 :: ('MESH:D013927', 'Disease') :: ['thrombus']
@entity95 :: (9986,Species) :: ['Rabbit']
