title: Non-invasive in vivo imaging of cardiac stem/progenitor cell biodistribution and retention after intracoronary and intramyocardial delivery in a swine model of chronic ischemia reperfusion injury.
abstract: The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. However, their optimal delivery route to the ischemic heart has not yet been assessed. This study was designed to determine by a non-invasive imaging technique (PET/CT) the biodistribution and acute retention of allogeneic pig CSC implanted by two different delivery routes, intracoronary (IC) and intramyocardial (IM), in a swine preclinical model of chronic ischemia-reperfusion.
  
  
  
  Ischemia-reperfusion was induced in six Goettingen hybrid minipigs by 90 min coronary artery occlusion followed by reperfusion. Thirty days later, animals were allocated to receive IC (n = 3) or NOGA®-guided IM injection (n = 3) of 50 million of18F-FDG/GFP-labeled allogeneic pig CSC. Acute retention was quantified by PET/CT 4 h after injection and cell engraftment assessed by immunohistochemical quantification of GFP+cells three days post-injection.
  
  
  
  Biodistribution of18F-FDG-labeled CSC was clearly visualized by PET/CT imaging and quantified. No statistical differences in acute cell retention (percentage of injected dose, %ID) were found in the heart when cells were administered by NOGA®-guided IM (13.4 ± 3.4%ID) or IC injections (17.4 ± 4.1%ID). Interestingly, engrafted CSC were histologically detected only after IM injection.
  
  
  
  PET/CT imaging of18F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection.
authors.affiliation: Department of Nuclear Medicine, IdisNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Collantes
authors.affiliation: Center for Applied Medical Research (CIMA) Cell Therapy Area, IdiSNA, Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelacho
authors.affiliation: Department of Nuclear Medicine, IdisNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: García-Velloso
authors.affiliation: Department of Cardiology and Cardiovascular Surgery, IdiSNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
authors.forename: Juán José
authors.initials: JJ
authors.lastname: Gavira
authors.affiliation: Center for Applied Medical Research (CIMA) Cell Therapy Area, IdiSNA, Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.affiliation: Coretherapix, Santiago Grisolía, n° 2 Parque Científico de Madrid, Tres Cantos, 28760, Madrid, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Palacios
authors.affiliation: Coretherapix, Santiago Grisolía, n° 2 Parque Científico de Madrid, Tres Cantos, 28760, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodriguez-Borlado
authors.affiliation: Coretherapix, Santiago Grisolía, n° 2 Parque Científico de Madrid, Tres Cantos, 28760, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Álvarez
authors.affiliation: Department of Nuclear Medicine, IdisNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Prieto
authors.affiliation: Small Animal Imaging Research Unit, Center for Applied Medical Research (CIMA), Universidad de Navarra, Pamplona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Ecay
authors.affiliation: Center for Applied Medical Research (CIMA) Cell Therapy Area, IdiSNA, Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Larequi
authors.affiliation: Department of Nuclear Medicine, IdisNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain. ipenuelas@unav.es.
authors.forename: Iván
authors.initials: I
authors.lastname: Peñuelas
authors.affiliation: Hematology and Cell Therapy, IdiSNA, Clínica Universidad de Navarra, Avda. Pío XII, 31080, Pamplona, Spain. fprosper@unav.es.
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
mesh_terms: D000818:Animals; D002469:Cell Separation; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D007267:Injections; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D000072078:Positron Emission Tomography Computed Tomography; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D034421:Sus scrofa; D014018:Tissue Distribution
chemical_list: D019788:Fluorodeoxyglucose F18; C083054:N-octanoylglucosylamine; D005944:Glucosamine
keywords: Cardiac stem/progenitor cells (CSC); Cell tracking; Myocardial infarction; PET/CT; Preclinical pig model