title: Radioiodide imaging and treatment of ARO cancer xenograft in a mouse model after expression of human sodium iodide symporter.
abstract: BACKGROUND
  Most undifferentiated and anaplastic thyroid carcinomas are not sensitive to 131I therapy due to their lost ability for iodide accumulation. This study aims to restore the iodide uptake by transferring and expressing human sodium iodide symporter (hNIS) in these cancer cells for 131I gene therapy.
  
  
  METHODS
  hNIS cDNA expression vector was transfected into wild-type anaplastic thyroid cancer cells (ARO-W) which do not concentrate iodide. Stable trasfected cells were isolated (ARO-S) and analyzed by RT-PCR, radioiodide uptake and immunocyto-chemistry staining. 131I imaging and treatment were performed on mice bearing ARO-W and ARO-S xenograft tumors and tumor volume was recorded.
  
  
  RESULTS
  The ARO-S cells showed clear hNIS expression on the cell membrane and accumulated 87-fold and 4.4-fold radioiodide of that of wild-type cells in vitro and in vivo, respectively. Radioiodide uptake was dependent on cell number and reached a maximum level at 20 minutes in vitro. The half life of radioiodide efflux was 12 minutes and 12 hours in vitro and in vivo, respectively. Administration of a therapeutic dose of 131I into mice bearing ARO-S tumors effectively inhibited tumor growth as compared to control mice.
  
  
  CONCLUSIONS
  Our results suggest the potential of hNIS-mediated 131I gene therapy on anaplastic thyroid cancer cells.
authors: Institute of Radiological Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors: Ya-Ju
authors: YJ
authors: Hsieh
authors: Chien-Chih
authors: CC
authors: Ke
authors: Ren-Shyan
authors: RS
authors: Liu
authors: Fu-Hui
authors: FH
authors: Wang
authors: Kam-Tsun
authors: KT
authors: Tang
authors: Chin-Wen
authors: CW
authors: Chi
authors: Fu-Du
authors: FD
authors: Chen
authors: Chen-Hsen
authors: CH
authors: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis* / Q000235:genetics; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D014183:Transplantation, Heterologous; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D027981:Symporters; D000099209:Sodium-Iodide Symporters