99mTc-pertechnetate uptake in hepatoma cells due to tissue-specific human sodium iodide symporter gene expression
99mTc-pertechnetate uptake in hepatoma cells due to tissue-specific human sodium iodide symporter gene expression
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DOI：
10.1016/j.nucmedbio.2006.01.011
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Haberkorn, Uwe
中科院分区：
文献类型：
--
作者：
Chen, Libo;Altman, Annette;Haberkorn, Uwe
钠碘转运蛋白(NIS)基因既是一种理想的报告基因，也是一种很有前途的治疗基因。经甲状腺摄取检查和放射性核素检查，99m-高铁酸盐在图像质量、操作程序和辐射剂量等方面均优于碘-131-碘。为此，我们研究了组织特异性表达的人钠碘转运体(HNIS)基因在人肝癌细胞(MH3924A)中表达的可行性。方法：将重组逆转录病毒载体稳定地导入MH3924A细胞，其中hNIS基因由小鼠白蛋白增强子/启动子(MAlb)驱动，并通过内部核糖体进入位点与潮霉素抗性基因偶联。I-125(-)摄取实验证实NIS在肝癌细胞中有功能性表达。结果：稳定表达99m-高铁酸盐的MH3924A细胞对99m-高铁酸盐的摄取量是野生型细胞的254倍。而~(99m)Tc-高铁酸盐在重组细胞外排出较快，半衰期不到2min。结论：利用白蛋白增强子/启动子和hNIS基因的重组逆转录病毒进行体内和体外组织特异性基因转移后，肿瘤细胞对99m-高铁酸盐的摄取增强。用常规伽马相机和99m-高铁酸盐对hNIS基因表达进行无创性定量监测是可行的。(C)2006 Elsevier Inc.保留所有权利。
The sodium iodide symporter (NIS) gene could be used as an ideal reporter gene as well as a promising therapeutic gene. Tc-99m-pertechnetate has proven to be more advantageous than I-131-iodide with respect to image quality, procedure and radiation dose ill examination of thyroid uptake and scintigraphy. Herein, we investigated the feasibility of monitoring human sodium iodide symporter (hNIS) gene expression with Tc-99m-pertechnetate in hepatoma cells (MH3924A) following tissue-specific expression.Methods: 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 I-125(-) uptake assay. The dynamic uptake and efflux of Tc-99m-pertechnetate was determined both in vitro and in vivo.Results: The Tc-99m-pertechnetate was up to 254-fold higher in stably transfected MH3924A cells than in wild-type cells. However, the in vitro efflux of Tc-99m-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 Tc-99m-pertechnetate and gamma camera.Conclusion: The current study demonstrates enhanced Tc-99m-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 Tc-99m-pertechnetate. (c) 2006 Elsevier Inc. All rights reserved.