Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation
| Autor: | Alain Meulemans, Jean-Marc Alsac, Martine Jandrot-Perrus, Michimasa Suzuki, Dominique Le Guludec, Frédéric Chaubet, Anne Petiet, Didier Letourneur, Liliane Louedec, Laure Bachelet-Violette, Jean-Baptiste Michel, François Rouzet |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Platelets
Male Pathology medicine.medical_specialty P-selectin In Vitro Techniques Endothelial activation chemistry.chemical_compound Ischemia Polysaccharides In vivo medicine Animals Tissue Distribution Radiology Nuclear Medicine and imaging Platelet cardiovascular diseases Annexin A5 Rats Wistar Thrombus Sodium Pertechnetate Tc 99m Tomography Emission-Computed Single-Photon Fucoidan business.industry Thrombosis Endocarditis Bacterial medicine.disease Immunohistochemistry Imaging agent Rats P-Selectin chemistry Rats Inbred Lew Aortic Valve Isotope Labeling Reperfusion Injury cardiovascular system Autoradiography Endothelium Vascular Radiopharmaceuticals business Preclinical imaging Aortic Aneurysm Abdominal |
| Zdroj: | Journal of Nuclear Medicine. 52:1433-1440 |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.110.085852 |
| Popis: | 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: platelet-rich 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:99mTc-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 99mTc-fucoidan in both settings was excellent. Conclusion: This study supports 99mTc-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. |
| Databáze: | OpenAIRE |
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