title: Dimeric [(68)Ga]DOTA-RGD peptide targeting αvβ 3 integrin reveals extracellular matrix alterations after myocardial infarction.
abstract: OBJECTIVE
  We evaluated a dimeric RGD-peptide, [(68)Ga]DOTA-E-[c(RGDfK)]2, for positron emission tomography (PET) imaging of myocardial integrin expression associated with extracellular matrix remodeling after myocardial infarction (MI) in rat.
  
  
  METHODS
  Male Sprague-Dawley rats were studied at 7 days and 4 weeks after MI induced by permanent ligation of the left coronary artery and compared with sham-operated controls.
  
  
  RESULTS
  In vivo imaging revealed higher tracer uptake in the infarcted area than in the remote non-infarcted myocardium of the same rats both at 7 days (MI/remote ratio, 2.25 ± 0.24) and 4 weeks (MI/remote ratio, 2.13 ± 0.37) post-MI. Compared with sham-operated rats, tracer uptake was higher also in the remote, non-infarcted myocardium of MI rats both at 7 days and 4 weeks where it coincided with an increased interstitial fibrosis. Standardized uptake values correlated well with the results of tracer kinetic modeling. Autoradiography confirmed the imaging results showing 5.1 times higher tracer uptake in the infarcted than remote area. Tracer uptake correlated with the amount of β3 integrin subunits in the infarcted area.
  
  
  CONCLUSIONS
  Our results show that integrin-targeting [(68)Ga]DOTA-E-[c(RGDfK)]2 is a potential tracer for monitoring of myocardial extracellular matrix remodeling after MI using PET.
authors.affiliation: Turku PET Centre, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Max
authors.initials: M
authors.lastname: Kiugel
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dijkgraaf
authors.forename: Ville
authors.initials: V
authors.lastname: Kytö
authors.forename: Semi
authors.initials: S
authors.lastname: Helin
authors.forename: Heidi
authors.initials: H
authors.lastname: Liljenbäck
authors.forename: Tiina
authors.initials: T
authors.lastname: Saanijoki
authors.forename: Cheng-Bin
authors.initials: CB
authors.lastname: Yim
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Saukko
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
mesh_terms: D000818:Animals; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid