Abstract
Background - Matrix metalloproteinase (MMP) activation plays a key role in vascular remodeling. RP782 is a novel indium 111In-labeled tracer with specificity for activated MMPs. We hypothesized that RP782 can detect injury-induced vascular remodeling in vivo. Methods and Results - Left common carotid artery injury was induced with a guidewire in apolipoprotein E -/- mice. Sham surgery was performed on the contralateral artery, which served as control for imaging experiments. Carotid wire injury led to significant hyperplasia and expansive remodeling over a period of 4 weeks. MMP activity, detected by in situ zymography, increased in response to injury and was maximal by 3 to 4 weeks after injury. RP782 (11.1 MBq) was injected intravenously into apolipoprotein E-/-mice at 1, 2, 3, and 4 weeks after left carotid injury. MicroSPECT imaging was performed at 2 hours and was followed by CT angiography to localize the carotid arteries. In vivo images revealed focal uptake of RP782 in the injured carotid artery at 2, 3, and 4 weeks. Increased tracer uptake in the injured artery was confirmed by quantitative autoradiography. Pretreatment with 50-fold excess nonlabeled tracer significantly reduced RP782 uptake in injured carotids, thus demonstrating uptake specificity. Weekly changes in the vessel-wall area closely paralleled and correlated with RP782 uptake (Spearman r=0.95, P=0.001). Conclusions - Injury-induced MMP activation in the vessel wall can be detected by RP782 microSPECT/CT imaging in vivo. RP782 uptake tracks the hyperplastic process in vascular remodeling and provides an opportunity to track the remodeling process in vivo.
Original language | English (US) |
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Pages (from-to) | 1953-1960 |
Number of pages | 8 |
Journal | Circulation |
Volume | 118 |
Issue number | 19 |
DOIs | |
State | Published - Nov 4 2008 |
Externally published | Yes |
Keywords
- Imaging
- Metalloproteinases
- Remodeling
ASJC Scopus subject areas
- Physiology (medical)
- Cardiology and Cardiovascular Medicine