title: Radiolabeled fucoidan as a p-selectin targeting agent for in vivo imaging of platelet-rich thrombus and endothelial activation.
abstract: 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
  (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: INSERM, U698, Cardiovascular Bioengineering, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Rouzet
authors.forename: Laure
authors.initials: L
authors.lastname: Bachelet-Violette
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Alsac
authors.forename: Michimasa
authors.initials: M
authors.lastname: Suzuki
authors.forename: Alain
authors.initials: A
authors.lastname: Meulemans
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Anne
authors.initials: A
authors.lastname: Petiet
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chaubet
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Dominique
authors.initials: D
authors.lastname: Le Guludec
authors.forename: Didier
authors.initials: D
authors.lastname: Letourneur
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging; D001021:Aortic Valve / Q000000981:diagnostic imaging; D001345:Autoradiography; D001792:Blood Platelets / Q000000981:diagnostic imaging*; D004697:Endocarditis, Bacterial / Q000000981:diagnostic imaging; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007511:Ischemia / Q000000981:diagnostic imaging; D007553:Isotope Labeling; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D011134:Polysaccharides / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000000981:diagnostic imaging; D013670:Sodium Pertechnetate Tc 99m / Q000737:chemistry; D013927:Thrombosis / Q000000981:diagnostic imaging*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D017304:Annexin A5; D019007:P-Selectin; D011134:Polysaccharides; D019275:Radiopharmaceuticals; C007789:fucoidan; D013670:Sodium Pertechnetate Tc 99m