Abstract 3198: RAGE-directed Imaging of Atherosclerotic Plaque in a Murine Model of Spontaneous Atherosclerosis
Introduction: The receptor for advanced glycation end products (RAGE) interacts with distinct molecules implicated in the development and progression of atherosclerosis. We assessed the hypothesis that 99mTc-labeled anti-RAGE F(ab’)2 fragments can be used as a noninvasive tool to access atherosclerotic lesion in apolipoprotein E deficient (apoE−/−) mice.
Methods: We developed a novel antibody in rabbits against the V-type Ig extracellular domain of RAGE. Five 20 wk apoE−/− mice fed a high-cholesterol diet plus 2 C57BL/6 mice were injected with 21.6 MBq (0.5 mCi) 99mTc-labeled anti-RAGE F(ab’)2 fragments and two 20 wk apoE−/− were injected with non-immune rabbit IgG. All mice were imaged on a high resolution parallel hole gamma camera 4 hr after injection (time based on blood pool clearance). Animals were sacrificed and the aortic tree dissected and photographed, and the root and proximal aorta sectioned for immunohistochemical staining after gamma scintillation counting.
Results: All five apoE−/− mice injected with 99mTc-labeled anti-RAGE F(ab’)2 fragments were scan positive. Both disease and antibody controls were scan negative. The mean percentage injected dose per gram (%ID/g) for scan positive was 3.35 and for scan negative <1.0. In vivo image and histology are shown below.
Conclusion: RAGE imaging identifies atherosclerotic lesions with vulnerable features..