Myocardial uptake of 99mTc-annexin-V and 111In-antimyosin-antibodies after ischemia-reperfusion in rats

Sarda‐Mantel, Laure; Hervatin, Florence; Michel, Jean‐Baptiste; Louedec, Liliane; Martet, G; Rouzet, François; Lebtahi, Rachida; Merlet, Pascal; Khaw, Ban‐An; Guludec, Dominique Le

doi:10.1007/s00259-007-0559-2

Cited by 18 publications

(20 citation statements)

References 32 publications

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“…Conversely, we found an opposite pattern in the setting of ischemia-reperfusion, with an uptake ratio twice (SPECT) and 3-fold (autoradiography) greater with radiolabeled fucoidan than annexin (24). In this setting, we can infer that the number of molecular targets is significantly different between annexin and fucoidan.…”

Section: P-selectin-targeted Imaging Agentsmentioning

confidence: 50%

“…The vegetation-to-background uptake ratio was 5.2 (2.7-9.1). On autoradiography, the 99m Tc-fucoidan uptake ratio was 17 (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Coregistration of autoradiography with histologic analysis performed after routine staining of tissue slices showed a clear delineation of the tracer uptake within the vegetations (Supplemental Fig.…”

Section: Endocarditic Vegetationsmentioning

confidence: 97%

“…Nine male Wistar rats (Janvier) were used in the study. The proximal left anterior descending coronary artery was occluded using a suture around a catheter for 20 min and then was reperfused by cutting the suture along the catheter in rats under general anesthesia (ketamine-xylazine) and positive pressure ventilation (24). Injection of the radiotracer was performed after 2 h of reperfusion.…”

Section: Experimental Modelsmentioning

confidence: 99%

“…Tissue samples were frozen and cut into transverse sections (20-mm thickness) that were exposed in a digital radioimager (Instant Imager; Packard) for 12 h. Quantification was performed by calculating the ratio between the activity (mean counts/mm 2 corrected for background) of the relevant sample (heart or aorta) and the activity of a region of interest drawn on a reference tissue (normal myocardium remote from the vegetation or ischemic area, or thoracic aorta) (21,23,24). In ischemiareperfusion studies, we estimated the cross-sectional extent of injured myocardium as the percentage of surface with increased radioactivity, compared with the surface of the left ventricular section on a slice perpendicular to the long axis of the heart taken in the midventricular segment.…”

Section: Autoradiographymentioning

confidence: 99%

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Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

Rouzet

Bachelet-Violette

Alsac³

et al. 2011

J Nucl Med

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116

107

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P-selectin expression is involved in the pathophysiology of biologically active arterial thrombus and endothelial activation after a transient ischemic event. Fucoidan is a polysaccharidic ligand of P-selectin, with a nanomolar affinity. In the present study, we propose a new approach of P-selectin molecular imaging based on radiolabeled fucoidan. Methods: Two kinds of experimental models were selected to evaluate the ability of radiolabeled fucoidan to detect P-selectin expression: plateletrich arterial thrombi (vegetations of infective endocarditis and arterial mural thrombus) and myocardial ischemia-reperfusion. These 2 settings were chosen because they were clinically relevant, and both were associated with an important overexpression of platelet and endothelial P-selectin, respectively. Results: 99m Tc-fucoidan SPECT was able to detect the presence of platelet-rich arterial thrombi in all animals, with a median target-to-background ratio of 5.2 in vegetations of endocarditis and 3.6 in mural aneurysmal thrombus, and to detect a persistent endothelial activation at 2 h after reperfusion. In this latter model, the magnitude of the signal was correlated with the extent of myocardium that underwent transient ischemia. The sensitivity of selectivity of the uptake and retention of 99m Tc-fucoidan in both settings was excellent. Conclusion: This study supports 99m Tc-fucoidan as a relevant imaging agent for in vivo detection of biologic activities associated with P-selectin overexpression, such as arterial thrombus and ischemic memory. Given the reported wide availability at a low cost, and its low toxicity, fucoidan seems to overcome some of the limitations of previous P-selectin-targeted imaging agents.Key Words: P-selectin; fucoidan; thrombus; ischemia; imaging J Nucl Med 2011; 52:1433-1440 DOI: 10.2967/jnumed.110.085852 P-sel ectin is an adhesion molecule expressed at the surface of endothelial cells and platelets on activation. It mediates leukocyte rolling on activated endothelium (1) and leukocyte trapping on platelet aggregates (2), through the interaction with its counterreceptor P-selectin glycoprotein ligand 1. In the cardiovascular field, P-selectin expression is involved in the pathophysiology of 2 settings of prominent clinical relevance: the renewal and growth of biologically active (at risk) arterial thrombus (2) and endothelial activation after an acute transient myocardial ischemic event referred to as ischemic memory (3). Activated platelets expose granular P-selectin on their membrane surface, and myocardial injury is associated with activation of endothelial cells resulting in Weibel-Palade bodies exocytosis and overexpression of adhesion molecules (1,4), which persists after ischemia has resolved. Therefore, P-selectin promotes platelet, endothelium, and leukocyte interactions, whatever the cardiovascular events, representing an important molecular target in acute and in chronic cardiovascular diseases.Consequently, many efforts have been made to develop imaging agents targeting P-selectin (5...

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Section: P-selectin-targeted Imaging Agentsmentioning

confidence: 50%

Section: Endocarditic Vegetationsmentioning

confidence: 97%

Section: Experimental Modelsmentioning

confidence: 99%

Section: Autoradiographymentioning

confidence: 99%

See 2 more Smart Citations

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

Rouzet

Bachelet-Violette

Alsac³

et al. 2011

J Nucl Med

Self Cite

116

107

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“…Several categories of molecular probes have been applied experimentally and clinically for imaging detection of myocardial cell death [21][22][23][24], but annexin V is the most extensively used probe for imaging apoptosis in diverse clinical circumstances [25]. Radioisotope-labeled annexin V has been used to detect cell death induced by ischemia and reperfusion injury in the myocardium [21,22,26].…”

Section: Discussionmentioning

confidence: 99%

Imaging Myocardial Ischemia and Reperfusion Injury via Cy5.5-Annexin V

Tian

Pan

2012

Nucl Med Mol Imaging

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Aim The aim of this article is to present the results of an imaging study of myocardial apoptosis induced by ischemia/reperfusion injury. Methods Twenty nude mice were randomly divided into an experimental group (10 mice) and control group (10 mice). In the experimental group, myocardial apoptosis was induced by ligation of the left anterior descending coronary artery (LAD) for 30 min. This was followed by reperfusion for 90 min. In the control group, the heart was exposed for the same length of time as in the experimental group. Cy5. 5-annexin V (25 μg) was injected into both sets of mice after the onset of reperfusion. At 90 min post-injection, the mice were imaged. The region of interest (ROI) was obtained, and the fluorescence intensity of the ROI was quantified. The animals were sacrificed, and myocardial apoptosis was assayed by TUNEL assay. Results Fluorescence intensity in the ischemia/reperfusion hearts was significantly higher than that in the control group (P<0.05). In the TUNEL assay, more apoptotic cells were observed in the experimental group than in the control group, correlating with imaging results. Conclusion Fluorescence imaging of Cy5.5-annexin V in a mouse model of myocardial ischemia/reperfusion can be used in vivo as a noninvasive means of detecting ischemia/reperfusion-induced apoptotic cells in the heart.

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Imaging of apoptosis in the heart with nanoparticle technology

Chen

Josephson

Sosnovik

2010

WIREs Nanomed Nanobiotechnol

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Apoptosis plays an important role in the loss of cardiomyocytes in both ischemic injury and heart failure. Pioneering work with single photon emission computed tomography imaging of 99Tc-annexin showed that cell death in the heart could be imaged in vivo. Over the last 5 years a significant amount of experience with annexin-labeled magnetic nanoparticles, principally AnxCLIO-Cy5.5, has also been gained. Here, we review the experience with AnxCLIO-Cy5.5 in the heart and compare this experience to that of earlier studies with 99Tc-annexin. The imaging of apoptosis with AnxCLIO-Cy5.5 provides valuable insights not only into molecular imaging in the heart but, more broadly, into the use of nanoparticle technology for molecular imaging in general.

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Myocardial uptake of 99mTc-annexin-V and 111In-antimyosin-antibodies after ischemia-reperfusion in rats

Cited by 18 publications

References 32 publications

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

Imaging Myocardial Ischemia and Reperfusion Injury via Cy5.5-Annexin V

Imaging of apoptosis in the heart with nanoparticle technology

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