Radionuclide Imaging And Therapy Of Hepatoma Following Tissue-Specific Expression Of Human Sodium/Iodide Symporter Gene

Objective : Benign thyroid diseases and thyroid cancer can be effectively diagnosed and treated by radioiodine, which is due to the expression of thyroid-specific genes such as NIS, thyroid peroxidase (TPO) and thyroglobulin (Tg). These proteins lead to trapping and organification of radioactive iodine in the target tissues. After the cloning of the NIS gene, several investigators explored the capacity of NIS gene transfer to induce radioiodine accumulation in non-thyroidal tumor cells. We investigated the feasibility of radionuclide imaging and therapy targeting hepatoma by tissue-specific expression of the human sodium iodide symporter (hNIS) gene directed by the murine albumin enhancer and promoter (mAlb).Methods: 1,Plasmid Constructs. The recombinant retroviral plasmid, pSIRmAlbhNISIVSIREShyg was constructed by standard plasmid subcloning techniques based on the pSIR self-inactivating retroviral vector. To assess the function and cell-specificity of mAlb, the AP1 enhancer and the TATA-like promoter (PTAL) region of pAP1-Luc (Clontech, USA) were replaced by mAlb with molecular clonal techniques, and pmAlb-Luc containing the luciferase gene under the control of mAlb was constructed. 2,Transient transfection and luciferase assay. The function and cell-specific transcriptional activity of mAlb was examined...