title: Ectopic expression of the sodium-iodide symporter enables imaging of transplanted cardiac stem cells in vivo by single-photon emission computed tomography or positron emission tomography.
abstract: OBJECTIVE
  We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m ((99m)Tc) or iodine 124 ((124)I), as a reporter gene for cell tracking by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging.
  
  
  BACKGROUND
  Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo.
  
  
  METHODS
  The human NIS complementary deoxyribonucleic acid was transduced into rat cardiac-derived stem cells (rCDCs) using lentiviral vectors. Rats were injected intramyocardially with up to 4 million NIS(+)-rCDCs immediately after left anterior descending coronary artery ligation. Dual isotope SPECT (or PET) imaging was performed, using (99m)Tc (or (124)I) for cell detection and thallium 201 (or ammonia 13) for myocardial delineation. In a subset of animals, high resolution ex vivo SPECT scans of explanted hearts were obtained to confirm that in vivo signals were derived from the cell injection site.
  
  
  RESULTS
  NIS expression in rCDCs did not affect cell viability and proliferation. NIS activity was verified in isolated transduced cells by measuring (99m)Tc uptake. NIS(+) rCDCs were visualized in vivo as regions of (99m)Tc or (124)I uptake within a perfusion deficit in the SPECT and PET images, respectively. Cells could be visualized by SPECT up to 6 days post-injection. Ex vivo SPECT confirmed that in vivo (99m)Tc signals were localized to the cell injection sites.
  
  
  CONCLUSIONS
  Ectopic NIS expression allows noninvasive in vivo stem cell tracking in the myocardium, using either SPECT or PET. The general approach shows significant promise in tracking the fate of transplanted cells participating in cardiac regeneration, given its ability to observe living cells using clinically applicable imaging modalities.
authors.affiliation: Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: John
authors.initials: J
authors.lastname: Terrovitis
authors.forename: Keng Fai
authors.initials: KF
authors.lastname: Kwok
authors.forename: Riikka
authors.initials: R
authors.lastname: Lautamäki
authors.forename: James M
authors.initials: JM
authors.lastname: Engles
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Barth
authors.forename: Eddy
authors.initials: E
authors.lastname: Kizana
authors.forename: Junichiro
authors.initials: J
authors.lastname: Miake
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Leppo
authors.forename: James
authors.initials: J
authors.lastname: Fox
authors.forename: Jurgen
authors.initials: J
authors.lastname: Seidel
authors.forename: Martin
authors.initials: M
authors.lastname: Pomper
authors.forename: Richard L
authors.initials: RL
authors.lastname: Wahl
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tsui
authors.forename: Frank
authors.initials: F
authors.lastname: Bengel
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
authors.forename: M Roselle
authors.initials: MR
authors.lastname: Abraham
mesh_terms: D053687:Adult Stem Cells / Q000637:transplantation*; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D017930:Genes, Reporter; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters