title: In vivo molecular imaging and radionuclide (131I) therapy of human nasopharyngeal carcinoma cells transfected with a lentivirus expressing sodium iodide symporter.
abstract: BACKGROUND
  Despite recent improvements in the survival rates for nasopharyngeal carcinoma (NPC), novel treatment strategies are required to improve distant metastasis-free survival. The sodium iodine symporter (NIS) gene has been applied for in vivo imaging and cancer therapy. In this study, we examined the potential of NIS gene therapy as a therapeutic approach in NPC by performing non-invasive imaging using 125I and 131I therapy in vivo.
  
  
  METHODS
  We constructed a lentiviral vector expressing NIS and enhanced green fluorescent protein (EGFP) under the control of the human elongation factor-1α (EF1α) promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE-2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT imaging; the therapeutic effects of treatment with 131I were assessed over 25 days by measuring tumor volume and immunohistochemical staining of the excised tumors.
  
  
  RESULTS
  qPCR, immunofluorescence and Western blotting confirmed that CNE-2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and xenografts took up and accumulated significantly more 125I than CNE-2Z cells and xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells expressed higher levels of NIS and caspase-3 and lower levels of Ki-67.
  
  
  CONCLUSIONS
  Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC. NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology* / Q000627:therapeutic use; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D011868:Radioisotopes / Q000494:pharmacology* / Q000627:therapeutic use; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D014018:Tissue Distribution; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D011868:Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters