title: (124)I-PET Assessment of Human Sodium Iodide Symporter Reporter Gene Activity for Highly Sensitive In Vivo Monitoring of Teratoma Formation in Mice.
abstract: OBJECTIVE
  Pluripotent stem cell (PSC)-based therapies possess great potential to restore the function of irreversibly damaged organs. PSCs can be differentiated in vitro into any cell type. However, pluripotent potential bears the risk of teratoma formation. In vivo monitoring of teratoma formation is indispensable, as 100 % purity of the cell preparation cannot be achieved. We aimed at establishing the human sodium iodide symporter (hNIS) as reporter gene for PET monitoring of teratoma formation.
  
  
  METHODS
  Murine PSC stably expressing hNIS were injected into the hind limbs of SCID mice to induce teratoma formation. Positron emission tomography (PET) scans were acquired weekly between days 14 and 42 after transplantation. Two teratomas were excised at each time point for histology and size measurement. Tracer uptake was correlated with teratoma weight. Specificity of tumoural iodine uptake was assessed by blocking hNIS in vivo with perchlorate.
  
  
  RESULTS
  Neither hNIS expression nor I-124 exposure adversely impacted viability or differentiation potential of PSCs. Iodine uptake was highly specific in teratomas, as in vivo blocking of hNIS with perchlorate led to uptake rates comparable to tracer uptake in non-transgene tumours. Tumour mass and tracer uptake showed a positive correlation.
  
  
  CONCLUSIONS
  This is the first study to generate stably hNIS-expressing murine PSCs. Since the differentiation potential was preserved, hNIS-expressing cells are suitable for PSC-based forward programming approaches. Teratoma formation from undifferentiated cells can be monitored in vivo by PET with high specificity on a quantitative level. Due to its anticipated lack of immunogenicity in humans, hNIS is a promising reporter gene for clinical translation.
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lehner
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Rostock, Germany.
authors.forename: Cajetan
authors.initials: C
authors.lastname: Lang
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kaissis
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Andrei
authors.initials: A
authors.lastname: Todica
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Mathias Johannes
authors.initials: MJ
authors.lastname: Zacherl
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Boening
authors.affiliation: Department of Internal Medicine II-Campus Grosshadern, University of Munich, Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Spitzweg
authors.affiliation: Institute of Veterinary Pathology, University of Munich, Munich, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Herbach
authors.affiliation: University Clinic of Internal Medicine III, Cardiology, Innsbruck Medical University, Innsbruck, Austria.|Munich Heart Alliance, University of Munich, Munich, Germany.
authors.forename: Wolfgang-Michael
authors.initials: WM
authors.lastname: Franz
authors.affiliation: Department of Nuclear Medicine, University of Rostock, Rostock, Germany.
authors.forename: Bernd Joachim
authors.initials: BJ
authors.lastname: Krause
authors.affiliation: Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Rostock, Germany.
authors.forename: Gustav
authors.initials: G
authors.lastname: Steinhoff
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Radiopharmacy and Experimental Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hacker
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Rostock, Germany. robert.david@med.uni-rostock.de.
authors.forename: Robert
authors.initials: R
authors.lastname: David
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D017930:Genes, Reporter; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D027981:Symporters / Q000235:genetics*; D013724:Teratoma / Q000000981:diagnostic imaging* / Q000473:pathology; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: In vivo monitoring; Reporter gene; Small animal PET; Sodium iodide symporter; Stem cell therapy; Teratoma formation