99mTc-pertechnetate uptake in hepatoma cells due to tissue-specific human sodium iodide symporter gene expression

Abstract

The sodium iodide symporter (NIS) gene could be used as an ideal reporter gene as well as a promising therapeutic gene. 99mTc-pertechnetate has proven to be more advantageous than 131I-iodide with respect to image quality, procedure and radiation dose in examination of thyroid uptake and scintigraphy. Herein, we investigated the feasibility of monitoring human sodium iodide symporter (hNIS) gene expression with 99mTc-pertechnetate in hepatoma cells (MH3924A) following tissue-specific expression. MH3924A cells were stably transfected with the recombinant retroviral vector, in which hNIS cDNA was driven by murine albumin enhancer/promoter (mAlb) and coupled to hygromycin resistance gene using an internal ribosomal entry site. Functional NIS expression in hepatoma cells was confirmed by an 125I(-) uptake assay. The dynamic uptake and efflux of 99mTc-pertechnetate was determined both in vitro and in vivo. The 99mTc-pertechnetate was up to 254-fold higher in stably transfected MH3924A cells than in wild-type cells. However, the in vitro efflux of 99mTc-pertechnetate out of recombinant cells was rapid with a half-life of less than 2 min. Further, the in vivo studies yielded clear images and quantitative data of mAlbhNIS-infected tumor xenografts using 99mTc-pertechnetate and gamma camera. The current study demonstrates enhanced 99mTc-pertechnetate uptake in hepatoma cells in vitro and in vivo following tissue-specific gene transfer using a recombinant retrovirus with the albumin enhancer/promoter and the hNIS gene. It is feasible to monitor hNIS gene expression noninvasively and quantitatively using conventional gamma camera and 99mTc-pertechnetate.