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Original Articles

Serial Noninvasive In Vivo Positron Emission Tomographic Tracking of Percutaneously Intramyocardially Injected Autologous Porcine Mesenchymal Stem Cells Modified for Transgene Reporter Gene Expression

Mariann Gyöngyösi, MD, PhD, FESC; Jeronimo Blanco, PhD; Teréz Marian, MD; Lajos Trón, MD; Örs Petneházy, PhD; Zsolt Petrasi, PhD; Rayyan Hemetsberger, MD; Julio Rodriguez, PhD; Gusztáv Font, VMD; Imre J. Pavo; István Kertész, MD; László Balkay, MD; Noemi Pavo, MSc; Aniko Posa, PhD; Miklos Emri, PhD; László Galuska, PhD; Dara L. Kraitchman, VMD, PhD; Johann Wojta, PhD; Kurt Huber, MD, FESC, FACC and Dietmar Glogar, MD, FESC

From the Department of Cardiology, Medical University of Vienna, Austria (M.G., R.H., I.J.P., N.P., A.P., J.W., D.G.); Centro de Investigación Cardiovascular (CSIC-ICCC), CIBER-BBN, Barcelona, Spain (J.B., J.R.); PET Centrum—Institute of Nuclear Medicine of the University of Debrecen, Hungary (T.M., L.T., I.K., L.B., M.E., L.G.); Institute of Diagnostic Imaging and Radiation Oncology, University of Kaposvar, Hungary (O.P., Z.P.); Downtown Animal Clinic, Budapest, Hungary (G.F.); The Johns Hopkins University, School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (D.L.K.); 3rd Department of Medicine (Cardiology and Emergency Medicine), Wilhelminenhospital, Vienna, Austria (K.H.).

Correspondence to Mariann Gyöngyösi, MD, PhD, FESC, Department of Cardiology, Medical University of Vienna, Wahringer Gurtel 18–20, A-1090 Vienna, Austria, E-mail mariann.gyongyosi{at}meduniwien.ac.at

Received June 8, 2008; accepted July 18, 2008.

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.

Methods and 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.

Key Words: cells • imaging • infarction • mapping • revascularization

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CLINICAL PERSPECTIVE

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