(124)I-PET Assessment of Human Sodium Iodide Symporter Reporter Gene Activity for Highly Sensitive In Vivo Monitoring of Teratoma Formation in Mice.
PURPOSE
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.


PROCEDURES
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.
['Lehner|Sebastian|S|', 'Lang|Cajetan|C|', 'Kaissis|Georgios|G|', 'Todica|Andrei|A|', 'Zacherl|Mathias Johannes|MJ|', 'Boening|Guido|G|', 'Spitzweg|Christine|C|', 'Herbach|Nadja|N|', 'Franz|Wolfgang-Michael|WM|', 'Krause|Bernd Joachim|BJ|', 'Steinhoff|Gustav|G|', 'Bartenstein|Peter|P|', 'Hacker|Marcus|M|', 'David|Robert|R|']
D000818:Animals D002454:Cell Differentiation D017930:Genes, Reporter D006801:Humans D007457:Iodine Radioisotopes D051379:Mice D049268:Positron-Emission Tomography D027981:Symporters D013724:Teratoma
Sodium iodide symporter Reporter gene In vivo monitoring Teratoma formation Small animal PET Stem cell therapy