Abstract 5544: ED-B Fibronectin Spect Imaging Detects Aortic Plaque Formation in vivo
The extracellular matrix protein ED-B fibronectin (ED-B) is upregulated in inflammatory atherosclerotic lesions and is associated with local macrophage accumulation. In the present study we evaluated whether a conjugate of 99mTc with the single chain antibody against ED-B (99mTC-anti-ED-B) can be used for in vivo detection of atherosclerotic plaque lesions in apolipoprotein E- deficient mice (apoE−/−) compared to wildtype control mice (apoE+/+).
Methods: 12 month old apoE−/− and apoE+/+ mice were studied by SPECT 4 hours after injection of 148 MBq of 99mTC-anti-ED-B. Finally mice were sacrificed and analyzed by autoradiography, histology, immunohistochemistry (IHC) and morphometry.
Results: In vivo SPECT imaging of apoE−/− mice demonstrated a significant signal activity in the thoracic area which colocalizes with the aortic arch and the supraaortic arteries. The activity corresponded to aortic lesion formation was 52.2±40.6 (1/1*ccm). Low activity was observed in apoE+/+ 9.4±4.9 (1/1*ccm), which had no significant lesion formation. The strongest signals were detected in the aortic root, the aortic arch and along the abdominal part of the aorta from apoE−/−. No vascular signal activity was seen in apoE+/+ after injection of 99mTC-anti-ED-B. The autoradiographic analysis of aortas from apoE−/− and apoE+/+, confirmed the in-vivo observation and demonstrated signal localization in typical plaque lesions, which significantly correlated with ED-B immunoreactivity, plaque lesion (r = 0.82, P<0.01) and local macrophage accumulation (IHC with Mac3 r = 0.89, P<0.01). There was a significant correlation between ED-B-radioactivity and macrophages (r= 0.93, P<0.01).
Conclusion: SPECT imaging using a 99mTc labelled antibody against ED-B fibronectin is a robust method to detect and assess inflammatory plaque lesion formation in-vivo and correlates with local macrophage accumulation.