Feasibility of sodium/iodide symporter gene as a new imaging reporter gene: comparison with HSV1-tk

Positron emission tomography (PET) imaging reporter genes, such as HSV1-tk and D₂ receptor genes, make it possible to visualise gene expression non-invasively and repetitively in vivo. However, these systems require the synthesis of complicated substrates and the availability of expensive PET equipment. Expression of the sodium/iodide symporter (NIS) gene can be easily monitored with radioiodines and technetium-99m using a gamma camera. To evaluate the possibility of using NIS as an imaging reporter gene, we compared its characteristics with those of the conventional HSV1-tk gene. The CM cell line was made by transfecting the HSV1-tk gene into CT-26 (mouse colon carcinoma cell line). The CTN and CMN cell lines were then made by transfecting the NIS gene into CT-26 and CM. We measured the uptake of iodine-125 iodovinyldeoxyuridine ([¹²⁵I]IVDU) and ¹²⁵I to evaluate the expression of the HSV1-tk and NIS genes, respectively. Each cell line was injected into four flank sites in Balb/c mice. The biodistribution study was performed after intravenously injecting [¹²⁵I]IVDU and ¹³¹I, and ¹³¹I scintigraphy was performed for the evaluation of NIS expression. In vitro studies indicated that CTN and CMN had 40- to 79-fold and 150- to 256-fold higher uptake of ¹²⁵I than CT-26 and CM, respectively. Furthermore, CM and CMN showed 57- to 69-fold higher uptake of [¹²⁵I]IVDU than CT-26 and CTN. NIS gene expression and ¹²⁵I accumulation were found to be directly correlated (R ²=0.923), as were HSV1-tk gene expression and [¹²⁵I]IVDU accumulation (R ²=0.956). Calculated signal per unit NIS and HSV1-tk mRNA expression was 23,240±3,755 cpm and 34,039±5,346 cpm, respectively. In vivo study indicated that CTN and CMN had 2.3- and 5.8-fold higher uptake of ¹³¹I than CT-26 and CM, and 1.8- and 3.5-fold higher uptake of [¹²⁵I]IVDU than CT-26 and CTN. Scintigraphy using ¹³¹I easily visualised CTN and CMN tumours. In conclusion, the NIS gene may be viewed as an imaging reporter gene with comparable performance to the HSV1-tk gene for monitoring target gene expression.