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Circulation. 2008 Nov 4;118(19):1953-60. doi: 10.1161/CIRCULATIONAHA.108.789743. Epub 2008 Oct 20.

Molecular imaging of activated matrix metalloproteinases in vascular remodeling.

Author information

  • 1Raymond and Beverly Sackler Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn., USA.

Abstract

BACKGROUND:

Matrix metalloproteinase (MMP) activation plays a key role in vascular remodeling. RP782 is a novel indium (111)In-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.

PMID:
18936327
[PubMed - indexed for MEDLINE]
PMCID:
PMC2637824
Free PMC Article
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