on July 30, 2008
Published online before print July 30, 2008, doi: 10.1161/CIRCIMAGING.108.797449
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Original Article |
Serial Non-Invasive In Vivo Positron Emission Tomographic (PET) Tracking Of Percutaneously intramyocardially Injected Autologous Porcine Mesenchymal Stem Cells Modified For Transgene Reporter Gene Expression
1 Department of Cardiology, Medical University of Vienna, Austria;
2 Centro de Investigación Cardiovascular (CSIC-ICCC), CIBER-BBN, Barcelona, Spain;
3 PET Centrum - Institute of Nuclear Medicine of the University of Debrecen, Hungary;
4 Institute of Diagnostic Imaging and Radiation Oncology, University of Kaposvar, Hungary;
5 Downtown Animal Clinic, Budapest, Hungary;
6 Russell H. Morgan Dept. of Radiology and Radiological Science, The Johns Hopkins University;
7 3rd Department of Medicine, Wilhelminenhospital Vienna, Austria
8 E-mail: mariann.gyongyosi{at}meduniwien.ac.at
Background—Porcine bone marrow-derived mesenchymal stem cells (MSC) 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 (positron emission tomography (PET) reporter gene) (LV-RL-RFP-tTK) for in vivo non-invasive tracking of the intramyocardially delivered MSC fate.
Methods and Results—A closed-chest, reperfused myocardial infarction (MI) was created in farm pigs. Sixteen days post-MI, LV-RL-RFP-tTK-MSCs were injected intramyocardially using electromechanical mapping guidance in the infarct border zone (n=7). PET-computed tomographic (CT) 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 post-LV-RL-RFP-tTK-MSC-treatment. Fusion imaging of the [18F]-FHBG PET–CT with magnetic resonance imaging (MRI) was used to determine the myocardial location of the injected LV-RL-RFP-tTK-MSCs. Seven days post-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 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% vs. 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 post-delivery using clinical PET scanners.
Key Words: cells • imaging • infarction • mapping • revascularization
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