Abstract 5791: Detection and Assessment of Atherosclerotic Plaques Using a Radiolabeled Molecular Imaging Probe Targeted to the Oxidized Low Density Lipoprotein Receptor LOX-1
Background and Objectives: Improved noninvasive imaging methods to characterize vulnerable atherosclerotic plaque are needed. Oxidized LDL and its receptor LOX-1 play a critical role in atherogenesis, e.g., induction of apoptosis, activation of MMPs, recruitment of inflammatory cells and contributing to plaque instability. We assessed atherosclerosis using a novel radiolabeled imaging probe targeted to LOX-1.
Materials and Methods: 20 Apo E −/− mice on Western diet for > 20 weeks were used. The targeted imaging probe (TP) consisted of liposomes decorated with anti-LOX-1 antibody, 111In and DiI fluorescence markers. Control probe (CP) carried nonspecific IgG. 24 hrs after iv probe injection, 5 mice per group were used for ex vivo fluorescence microscopy. The other 5 mice were used for microSPECT/CT, followed by ex vivo aorta phosphor imaging.
Results: In vitro binding study demonstrated selective probe targeting to LOX-1. In vivo fluorescence imaging showed that TP, but not CP, bound mainly to the shoulder area of some plaques. TP signal (yellow, A&B) in plaques was co-localized with the areas of apoptosis (green, A) and elevated MMP9 (green, B) expression. MicroSPECT imaging showed hotspots in the aortic arch (arrows, C) in all TP-injected mice (n=5) corresponding with focal uptake areas observed by phosphor imaging of the excised aortas (D). Little CP was bound to plaques as detected by fluorescence, microSPECT or phosphor imaging (E&F).
Conclusions: LOX-1 can be used as a target for molecular imaging of atherosclerotic plaque. Imaging of LOX-1 may also predict plaque vulnerability.