Quantification of sodium-iodide symporter positive murine embryonic stem cells using [124I]-micro-PET reporter gene imaging in the mouse model of teratoma

Objectives Intramyocardially transplanted stem cells can be visualized over the course of hours up to several days by means of in-vitro labeling as well as up to several weeks using reporter gene imaging. Methods for the quantification of these cells in-vivo have not been described as of yet. We aimed to establish a method for the quantification of transplanted stem cells using [124I]-micro-PET reporter gene imaging.

Methods Sodium-iodide symporter (NIS) positive murine embryonic stem cells (ESNIS+) were transplanted into the hind legs of SCID mice. [124I]-micro-PET scans oft the teratomas were conducted on days 9, 14, 19, 26, 28, 33 and 39 (11 MBq, 45 min p.i. over 30 min). Size and weight of the teratomas as surrogate marker for the cell count were assessed on the corresponding days ex-vivo. The percentage of the injected dose (%ID) was calculated. NIS negative teratomas (ESNIS-) were used as a control. NIS positive teratomas were blocked with sodiumperchlorate (ESNIS+bl) to assess the specificity of the tracer uptake. Immunohistochemical staining was used for histological correlation.

Results %ID and weight of the teratomas showed a good correlation (R=0.54, P=0.03). ESNIS+ teratomas showed a significantly higher [124I]-uptake (4.6±0.004%) than ESNIS+bl (1.3±0.003%) and ESNIS- (1.4±0.005%) teratomas (ESNIS+ vs. ESNIS+bl, P=0.02; ESNIS+ vs. ESNIS-, P=0.01). Immunohistochemical staining showed the presence of NIS in ESNIS+ and ESNIS+bl teratomas, but not in ESNIS- teratomas.

Conclusions NIS showed a stable expression in murine embryonic stem cells. It could be detected over the course of 39 days with immunohistochemical staining. It was possible to detect an quantify NIS with [124I]-micro-PET in-vivo over the same space of time. [124I]-Uptake and weight as a surrogate marker for the cell count show a good correlation.