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
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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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