Non-Invasive Molecular Imaging of Fibrosis Using a Collagen-Targeted Peptidomimetic of the Platelet Collagen Receptor Glycoprotein VI 英文参考文献.docVIP

Non-Invasive Molecular Imaging of Fibrosis Using a Collagen-Targeted Peptidomimetic of the Platelet Collagen Receptor Glycoprotein VI 英文参考文献.doc

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Non-Invasive Molecular Imaging of Fibrosis Using a Collagen-Targeted Peptidomimetic of the Platelet Collagen Receptor Glycoprotein VI 英文参考文献

Non-InvasiveMolecularImagingofFibrosisUsinga Collagen-TargetedPeptidomimeticofthePlatelet CollagenReceptorGlycoproteinVI JulienMuzard1,5.,LaureSarda-Mantel2,5,6.,Ste′phaneLoyau1,5,AlainMeulemans2,5,6 ,Liliane Louedec1,5,ClaudieBantsimba-Malanda4,5,FlorenceHervatin5,Joe¨lleMarchal-Somme4,5,JeanBaptiste Michel1,5,6,DominiqueLeGuludec2,5,6,PhilippeBilliald3,MartineJandrot-Perrus1,5,6* 1INSERM,U698,Ho?pitalBichat,Paris,France,2INSERM,U773,CRB3,Faculte′ XavierBichat,Paris,France,3MuseumNationald’HistoireNaturelle,CNRS-FRE3206,Paris, France,4INSERM,U700,Faculte′ XavierBichat,Paris,France,5Universite′ Paris7,Paris,France,6AP-HP,Ho?pitalBichat,Paris,France Abstract Background:Fibrosis,whichischaracterizedbythepathologicalaccumulationofcollagen,isrecognizedasanimportant feature of many chronic diseases, and as such, constitutes an enormous health burden. We need non-invasive specific methodsfortheearlydiagnosisandfollow-upoffibrosisinvariousdisorders.Collagentargetingmoleculesarethereforeof interestforpotentialinvivoimagingoffibrosis.Inthisstudy,wedevelopedacollagen-specificprobeusinganewapproach thattakesadvantageoftheinherentspecificityofGlycoproteinVI(GPVI),themainplateletreceptorforcollagensIandIII. Methodology/PrincipalFindings:Ananti-GPVIantibodythatneutralizescollagen-bindingwasusedtoscreenabacterial random peptide library. A cyclic motif was identified, and the corresponding peptide (designated collagelin) was synthesized.Solid-phasebindingassaysandhistochemicalanalysisshowedthatcollagelinspecificallyboundtocollagen (Kd1027M)invitro,andlabelledcollagenfibersexvivoonsectionsofrataortaandrattail.Collagelinisthereforeanew specificprobeforcollagen.Thesuitabilityofcollagelinasaninvivoprobewastestedinaratmodelofhealedmyocardial infarctions(MI).InjectingTc-99m-labelledcollagelinandscintigraphicimagingshowedthatuptakeoftheprobeoccurredin thecardiacareaofratswithMI,butnotincontrols.Postmortemautoradiographyandhistologicalanalysisofheartsections showed that the labe

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