Scintigraphic Imaging of Matrix Metalloproteinase Activity in the Arterial Wall In Vivo

Schäfers, Michael; Riemann, Burkhard; Kopka, Klaus; Breyholz, Hans-Jörg; Wagner, Stefan; Schäfers, Klaus P.; Law, Marilyn P.; Schober, Otmar; Levkau, Bodo

doi:10.1161/01.cir.0000129088.49276.83

Cited by 202 publications

(148 citation statements)

References 18 publications

(18 reference statements)

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“…These probes may be useful to complement other techniques used to study MMPs, including zymography and scintigraphy. 24 Our results also indicate that these probes can be used to monitor enzyme activity on a microscopic level and can be coupled with flow cytometry. Similar NIRF probes have been coupled with optical tomography methods for in vivo imaging.…”

Section: Discussionsupporting

confidence: 52%

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Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction

et al. 2005

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Background-We used a molecular probe activated by protease cleavage to image expression of matrix metalloproteinases (MMPs) in the heart after myocardial infarction. Methods and Results-We synthesized and characterized a near-infrared fluorescent (NIRF) probe that is activated by proteolytic cleavage by MMP2 and MMP9. The NIRF probe was injected into mice at various time points up to 4 weeks after myocardial infarction induced by ligation of the left anterior descending coronary artery. NIRF imaging of MMP activity increased in the infarct region, with maximal expression at 1 to 2 weeks, persisting to 4 weeks. Zymography and real-time polymerase chain reaction analysis showed that MMP9 expression is increased at 2 to 4 days, and MMP2 expression is increased at 1 to 2 weeks. Dual-label confocal microscopy showed colocalization of NIRF imaging with neutrophils on day 2, and flow cytometric analysis confirmed that NIRF signal is associated with leukocytes in the infarct zone. Conclusions-This study demonstrates that the activity of MMPs in the myocardium may be imaged by use of specific activity-dependent molecular probes. (Circulation. 2005;111:1800-1805.)

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Section: Discussionsupporting

confidence: 52%

“…This approach complements existing methods for after MMP levels and activity, such as zymography, immunohistochemistry, Western blotting, and scintigraphy. 24 …”

Section: See P 1730mentioning

confidence: 99%

Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction

et al. 2005

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“…MMPs have therefore been considered ideal targets for molecular imaging of vulnerable plaque. In preclinical models of atherosclerosis, 123 I-or 125 I-labeled CGS 27023A, a broad-spectrum MMP inhibitor (32), and RP-805, a 99m Tc-labeled broad-spectrum MMP-inhibiting macrocyclic compound, have been shown to bind to atherosclerotic plaque (33,34).…”

Section: Matrix Remodeling By Mmpmentioning

confidence: 99%

Molecular Imaging of Vulnerable Coronary Plaque: A Pathophysiologic Perspective

et al. 2017

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Atherothrombotic events in coronary arteries are most often due to rupture of unstable plaque resulting in myocardial infarction. Radiolabeled molecular imaging tracers directed toward cellular targets that are unique to unstable plaque can serve as a powerful tool for identifying high-risk patients and for assessing the potential of new therapeutic approaches. Two commonly available radiopharmaceuticals-18 F-FDG and 18 F-NaF-have been used in clinical research for imaging coronary artery plaque, and ongoing clinical studies are testing whether there is an association between 18 F-NaF uptake and future atherothrombotic events. Other, less available, tracers that target macrophages, endothelial cells, and apoptotic cells have also been tested in small groups of patients. Adoption of molecular imaging of coronary plaque into clinical practice will depend on overcoming major hurdles, ultimately including evidence that the detection of unstable plaque can change patient management and improve outcomes. Cardi ovascular disease is the number one cause of death in the United States, despite numerous advances in prevention, diagnosis, and treatment (1). Nearly half these deaths are due to acute myocardial infarction, and up to 75% of myocardial infarctions are the result of an acute thrombotic event after rupture of coronary artery plaque. Rupture-prone plaques often do not cause significant obstruction (2) and are not detectable by stress imaging, the approach most commonly used to assess risk. Identification of the rupture-prone, or vulnerable, plaque could add prognostic value and thus has become a major focus in cardiovascular diagnostics. Molecular imaging with radiopharmaceuticals has the potential to play a key role in the assessment of vulnerable plaque. In this review, we will describe advances in molecular imaging in the context of the pathophysiology associated with plaque growth and vulnerability. TECHNICAL CHALLENGES IN PET IMAGING OF CORONARY PLAQUEImaging of coronary plaque with PET tracers is difficult because of the limited spatial resolution of PET, the small size of coronary plaque, and blurring caused by cardiac and respiratory motion. To partially mitigate motion of the coronary arteries, some investigators have performed enddiastolic imaging using only a part of the PET scan, but at the expense of increased image noise (3). We are exploring computational motion correction techniques that can potentially improve image quality, and we have demonstrated that these corrections can increase the target-to-background ratios of tracer uptake within coronary plaque and reduce image noise. The approach is likely to improve detection of small foci of tracer uptake within the coronary arteries (4). THE BIOLOGY OF CORONARY PLAQUEAtherosclerotic plaque develops in response to endothelial injury and entry of low-density-lipoprotein cholesterol into the intimal layer of the vessel wall. In response to this injury, monocytes are recruited into the vessel wall and differentiate into macrophages, which take up modifi...

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“…CGS 27023A, a non-specific inhibitor that binds to the active catalytic domain of MMPs, has dominant uptake in the apolipoprotein E-deficient mouse by using micro-PECT/CT. Although this technique can be used to detect activation of MMPs in aortic disease, it cannot differentiate the type of effect of MMPs in inflammation of the aorta (89). Compared with substrates, inhibitors interact with MMPs in a 1:1 manner and have no signal magnification.…”

Section: Mmpmentioning

confidence: 99%

Molecular targets in aortic aneurysm for establishing novel management paradigms

Zhu

et al. 2017

J. Thorac. Dis.

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Aortic aneurysm (AA) is a lethal disease and presents a large challenge for surgeons in the clinic.Although surgical management remains the major choice of AA, operative mortality remains high. With advances in understanding of the mechanisms of AAs, molecular targets, such as matrix metalloproteinases (MMPs), D-dimer, and inflammation markers, including C-reactive protein, interleukins and phagocytes, are important in the pathology of development of AA. These markers may become important for improving the diagnostic quality and provide more therapeutic choices for treatment of AA. Although these new markers require long-term trials before they can be translated into the clinic, they can still be helpful in determining new directions. The main aim of this review is to discuss the current findings of molecular targets in progression of AA and discuss the potential application of these new targets for managing this disease.

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Scintigraphic Imaging of Matrix Metalloproteinase Activity in the Arterial Wall In Vivo

Cited by 202 publications

References 18 publications

Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction

Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction

Molecular Imaging of Vulnerable Coronary Plaque: A Pathophysiologic Perspective

Molecular targets in aortic aneurysm for establishing novel management paradigms

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