title: Serial noninvasive in vivo positron emission tomographic tracking of percutaneously intramyocardially injected autologous porcine mesenchymal stem cells modified for transgene reporter gene expression.
abstract: BACKGROUND
  Porcine bone marrow-derived mesenchymal stem cells (MSCs) were stably transfected with a lentiviral vector for transgene expression of the trifusion protein renilla luciferase, red fluorescent protein and herpes simplex truncated thymidine kinase (LV-RL-RFP-tTK; positron emission tomography [PET] reporter gene) for in vivo noninvasive tracking of the intramyocardially delivered MSC fate.
  
  
  RESULTS
  A closed-chest, reperfused myocardial infarction was created in farm pigs. Sixteen days after myocardial infarction, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic metabolic and perfusion imaging was performed after an intravenous injection of 10 mCi [18F]-FHBG and 13N-ammonia PET at 30+/-2 hours and 7 days after LV-RL-RFP-tTK-MSC treatment. Fusion imaging of the [18F]-FHBG PET-computed tomography with MRI was used to determine the myocardial location of the injected LV-RL-RFP-tTK-MSCs. Seven days after injections, [18F]-FHBG PET showed a decreased cardiac uptake with a mild increased pericardial and pleura uptake in the treated animals, which was confirmed by the measurement of luciferase activity. At 10 days, infarct size by MRI in the LV-RL-RFP-tTK-MSC-treated animals was smaller than controls (n=7) (23.3+/-1.5% versus 30.2+/-3.5%, P<0.005). The presence of the LV-RL-RFP-tTK-MSCs (5.8+/-1.1% of the injected cells) in the myocardium 10 days after intramyocardial delivery was confirmed histologically.
  
  
  CONCLUSIONS
  Reporter gene imaging enables the tracking of the persistence of viable LV-RL-RFP-tTK-MSC in the peri-infarcted porcine myocardium at 10 days after delivery using clinical PET scanners.
authors.affiliation: Department of Cardiology, Medical University of Vienna, Wahringer Gurtel 18-20, Vienna, Austria. mariann.gyongyosi@meduniwien.ac.at
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.forename: Jeronimo
authors.initials: J
authors.lastname: Blanco
authors.forename: Teréz
authors.initials: T
authors.lastname: Marian
authors.forename: Lajos
authors.initials: L
authors.lastname: Trón
authors.forename: Ors
authors.initials: O
authors.lastname: Petneházy
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Petrasi
authors.forename: Rayyan
authors.initials: R
authors.lastname: Hemetsberger
authors.forename: Julio
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Gusztáv
authors.initials: G
authors.lastname: Font
authors.forename: Imre J
authors.initials: IJ
authors.lastname: Pavo
authors.forename: István
authors.initials: I
authors.lastname: Kertész
authors.forename: László
authors.initials: L
authors.lastname: Balkay
authors.forename: Noemi
authors.initials: N
authors.lastname: Pavo
authors.forename: Aniko
authors.initials: A
authors.lastname: Posa
authors.forename: Miklos
authors.initials: M
authors.lastname: Emri
authors.forename: László
authors.initials: L
authors.lastname: Galuska
authors.forename: Dara L
authors.initials: DL
authors.lastname: Kraitchman
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Dietmar
authors.initials: D
authors.lastname: Glogar
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes; D015870:Gene Expression; D017930:Genes, Reporter; D006147:Guanine / Q000031:analogs & derivatives; D006321:Heart / Q000000981:diagnostic imaging*; D007267:Injections; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D049268:Positron-Emission Tomography; D034421:Sus scrofa; D014162:Transfection; D019076:Transgenes
chemical_list: C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D005462:Fluorine Radioisotopes; D006147:Guanine