title: Multimodality molecular imaging to monitor transplanted stem cells for the treatment of ischemic heart disease.
abstract: OBJECTIVE
  Non-invasive techniques to monitor the survival and migration of transplanted stem cells in real-time is crucial for the success of stem cell therapy. The aim of this study was to explore multimodality molecular imaging to monitor transplanted stem cells with a triple-fused reporter gene [TGF; herpes simplex virus type 1 thymidine kinase (HSV1-tk), enhanced green fluorescence protein (eGFP), and firefly luciferase (FLuc)] in acute myocardial infarction rat models.
  
  
  METHODS
  Rat myocardial infarction was established by ligating the left anterior descending coronary artery. A recombinant adenovirus carrying TGF (Ad5-TGF) was constructed. After transfection with Ad5-TGF, 5 × 10(6) bone marrow mesenchymal stem cells (BMSCs) were transplanted into the anterior wall of the left ventricle (n = 14). Untransfected BMSCs were as controls (n = 8). MicroPET/CT, fluorescence and bioluminescence imaging were performed. Continuous images were obtained at day 2, 3 and 7 after transplantation with all three imaging modalities and additional images were performed with bioluminescence imaging until day 15 after transplantation.
  
  
  RESULTS
  High signals in the heart area were observed using microPET/CT, fluorescence and bioluminescence imaging of infarcted rats injected with Ad5-TGF-transfected BMSCs, whereas no signals were observed in controls. Semi-quantitative analysis showed the gradual decrease of signals in all three imaging modalities with time. Immunohistochemistry assays confirmed the location of the TGF protein expression was the same as the site of stem cell-specific marker expression, suggesting that TGF tracked the stem cells in situ.
  
  
  CONCLUSIONS
  We demonstrated that TGF could be used as a reporter gene to monitor stem cells in a myocardial infarction model by multimodality molecular imaging.
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China; Department of PET Center, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Lan
authors.affiliation: Molecular Imaging Program at Stanford and Bio-X Program, Stanford University, Stanford, California, United States of America.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D057054:Molecular Imaging / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods*; D017202:Myocardial Ischemia / Q000628:therapy*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*