%0 Journal Article
%T Quantitative Longitudinal Imaging of Vascular Inflammation and Treatment by Ezetimibe in apoE Mice by FMT Using New Optical Imaging Biomarkers of Cathepsin Activity and Integrin
%A Shu-An Lin
%A Manishkumar Patel
%A Donna Suresch
%A Brett Connolly
%A Bagna Bao
%A Kevin Groves
%A Milind Rajopadhye
%A Jeffrey D. Peterson
%A Michael Klimas
%A Cyrille Sur
%A Bohumil Bednar
%J International Journal of Molecular Imaging
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/189254
%X Inflammation as a core pathological event of atherosclerotic lesions is associated with the secretion of cathepsin proteases and the expression of integrin. We employed fluorescence molecular tomographic (FMT) noninvasive imaging of these molecular activities using cathepsin sensing (ProSense, CatB FAST) and integrin (IntegriSense) near-infrared fluorescence (NIRF) agents. A statistically significant increase in the ProSense and IntegriSense signal was observed within the chest region of apoE£¿/£¿ mice ( ) versus C57BL/6 mice starting 25 and 22 weeks on high cholesterol diet, respectively. In a treatment study using ezetimibe (7£¿mg/kg), there was a statistically significant reduction in the ProSense and CatB FAST chest signal of treated ( ) versus untreated apoE£¿/£¿ mice at 31 and 21 weeks on high cholesterol diet, respectively. The signal of ProSense and CatB FAST correlated with macrophage counts and was found associated with inflammatory cells by fluorescence microscopy and flow cytometry of cells dissociated from aortas. This report demonstrates that cathepsin and integrin NIRF agents can be used as molecular imaging biomarkers for longitudinal detection of atherosclerosis, and cathepsin agents can monitor anti-inflammatory effects of ezetimibe with applications in preclinical testing of therapeutics and potentially for early diagnosis of atherosclerosis in patients. 1. Introduction Atherosclerosis, a progressive inflammatory disease, results in the development of plaques within the arterial walls that may contain intracellular and extracellular lipids, a variety of inflammatory cells, extracellular matrix, smooth muscle cells, fibroblasts, and calcification [1¨C4]. Acute coronary syndrome (ACS) and stroke are typically associated with the development of vulnerable plaques. A vulnerable plaque is characterized by an accumulation of macrophages and macrophage-derived foam cells, degradation of the extracellular matrix, and the formation of a necrotic core, neoangiogenesis, intraplaque hemorrhage, and a thin fibrous cap [3, 5¨C7]. Thus, the prevention of a heart attack or stroke would benefit from the early detection of the biological processes resulting in the inflammation and neoangiogenesis associated with atherosclerotic lesions. The noninvasive detection of atherosclerotic plaque has been clinically limited mostly to the measurements of arterial stenosis in selected arterial beds [8¨C11]. Such measurements have been shown to be poor predictors of clinical outcomes, thus stimulating further research into the biology of atherosclerotic lesions and
%U http://www.hindawi.com/journals/ijmi/2012/189254/