Inflammation as a core pathological event of atherosclerotic lesions is associated with the secretion of
cathepsin proteases and the expression of α(v)β(3)
integrin. We employed fluorescence molecular tomographic (FMT) noninvasive imaging of these molecular activities using
cathepsin sensing (ProSense, CatB FAST) and α(v)β(3)
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 (P < 0.05) 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 (P < 0.05) 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 α(v)β(3)
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.