Radioiodide imaging and treatment of ARO cancer xenograft in a mouse model after expression of human sodium iodide symporter.
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.
Hsieh
Ya-Ju
YJ
Institute of Radiological Sciences, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Ke
Chien-Chih
CC
Liu
Ren-Shyan
RS
Wang
Fu-Hui
FH
Tang
Kam-Tsun
KT
Chi
Chin-Wen
CW
Chen
Fu-Du
FD
Lee
Chen-Hsen
CH
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
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D027981:Symporters; D000099209:Sodium-Iodide Symporters