Abstract 13098: Integrin-Targeted MicroSPECT-CT Imaging of Inflamed Atherosclerotic Plaques in Mice

Abstract

Background and aim. αVβ3 integrin is expressed in endothelial cells and macrophages of atherosclerotic plaques and may represent a valuable marker of plaque vulnerability. To test this, we evaluated whether the integrin specific tracer 99mTc-NC100692 can be used for imaging inflamed atherosclerotic lesions in mice.

Methods. Hyperlipidemic ApoE-/- mice on a Western diet (n=7) and normally fed adult C57BL6 control mice (n=4) were injected with NC100692 (51.8 ± 3.7 MBq). A blocking peptide was infused immediately before the tracer injection in 3 additional ApoE-/- mice that served as control. After 90 min, the animals were imaged with a µSPECT system, and immediately thereafter on a MDCT system to obtain contrast-enhanced images of the aorta. Images from both modalities were fused and the signal was quantified in the aortic arch and in the vena cava for blood pool activity substraction. The aorta was carefully dissected after imaging for gamma well counting and histology. Results. A significantly higher tracer uptake (defined as the counts/pixel ratio between the aortic arch and the vena cava) was observed between the ApoE-/- mice and 2 control mice groups (1.56 ± 0.33 vs 0.82 ± 0.24 (C57BL6) vs 0.98 ± 0.11 (blocking peptide) respectively; p<0.05, see graph). Furthermore, a significant tracer activity was observed by gamma counting in the aorta of ApoE-/- mice compared with 2 control mice groups (0.015 ± 0.004 vs 0.007 ± 0.006 µCi/mg of tissue; p<0.05). Finally, immunostaining with antibodies against integrin correlated well with the presence of macrophages into atherosclerotic lesions of ApoE-/- mice.

Conclusion. NC100692 allows for the in vivo detection of inflamed atherosclerotic plaques in mice and may thus represent an interesting non invasive approach for identifying vulnerable plaques in patients.