Molecular Imaging of Activated Matrix Metalloproteinases in Vascular Remodeling

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 Ϫ/Ϫ 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 Ϫ/Ϫ 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 rϭ0.95, Pϭ0.001

Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development

“…In situ zymography was performed according to manufacturer's instructions and as described elsewhere (32). In brief, aortic sections from scr-miR- as well as anti-29b- and pre-29b-transduced mice were exposed to DQ gelatin (10 μg/ml; Invitrogen) and 1% agarose solution (ratio 1:10).…”

Molecular Imaging of the Cardiac Extracellular Matrix

“…[92][93][94][95] Specificity of the tracer and correlation with MMP2 and MMP9 activity and presence of macrophages was shown. 92 Also, imaging with Tc-RP805, has been undertaken in animal models of MI, 90 atherosclerosis, 96 carotid damage, 97 and carotid aneurysms. 98 The feasibility of MRI of MMP using gadolinium-labeled probe (P947) has been demonstrated in rat model of aortic aneurysm, 99 mouse 100,101 and rabbit 100,101 models of atherosclerosis, and excised human carotid atherosclerotic plaques.…”

Integration of Infarct Size, Tissue Perfusion, and Metabolism by Hybrid Cardiac Positron Emission Tomography/Computed Tomography

“…This hypothesis would need to be tested in future studies that include follow-up observations. Importantly, for the purpose of detecting pathophysiological mechanisms that precede adverse ventricular remodeling, other more specific radiotracers targeting inflammation or other key processes such as MMP activity 32 or neurohumoral activation 33 may be preferable over the less specific FDG. Combination with CT as a morphological technique in the PET-CT environment may be even more attractive for these compounds, which are expected to show a weaker albeit more specific molecular signal that would require additional information for accurate localization.…”