Integrin-Targeted Imaging of Inflammation in Vascular Remodeling
Objective—Inflammation plays a key role in the development of vascular diseases. Monocytes and macrophages express αvβ3 integrin. We used an αv integrin-specific tracer, 99mTc-NC100692, to investigate integrin-targeted imaging for detection vessel wall inflammation.
Methods and Results—The binding of a fluorescent homologue of NC100692 to αvβ3 on human monocytes and macrophages was shown by flow cytometry. Vessel wall inflammation and remodeling was induced in murine carotid arteries through adventitial exposure to CaCl2. NC100692 microSPECT/CT imaging was performed after 2 and 4 weeks and showed significantly higher uptake of the tracer in CaCl2-exposed left carotids compared with sham-operated contralateral arteries. Histological analysis at 4 weeks demonstrated significant remodeling of left carotid arteries and considerable macrophage infiltration, which was confirmed by real-time polymerase chain reaction. There was no significant difference in normalized αv, β3, or β5 mRNA expression between right and left carotid arteries. Finally, NC100692 uptake strongly correlated with macrophage marker expression in carotid arteries.
Conclusion—NC100692 imaging can detect vessel wall inflammation in vivo. If further validated, αv-targeted imaging may provide a noninvasive approach for identifying patients who are at high risk for vascular events and tracking the effect of antiinflammatory treatments.
- Received May 20, 2011.
- Accepted September 6, 2011.
- © 2011 American Heart Association, Inc.