In vitro and in vivo properties of a human anaplastic thyroid carcinoma cell line transfected with the sodium iodide symporter gene.
To evaluate the feasibility of radionuclide gene therapy, we investigated the effect of sodium iodide symporter (NIS) gene transfection on the uptake of some beta- and gamma-emitters in human anaplastic thyroid cancer. NIS gene was transfected into human anaplastic cancer ARO cells using liposome (ARO-N) and its expression was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Iodide uptake by ARO-N was 109 times higher than by ARO, and 99mTc and 188Re uptake by ARO-N were 21 and 47 times higher than by ARO, respectively. The half-lives of radionuclides (125I, 99mTc, and 188Re) retention in the cells were about 12, 3 and 4 min, respectively. Biodistribution studies showed that ARO-N tumors accumulated higher amounts of radionuclides than ARO tumors. The mean accumulations of 125I, 99mTc, and 188Re in ARO-N tumors were 18.3 +/- 8.7, 14.6 +/- 7.1 and 23.2 +/- 3.5% injected dose per gram (ID/g) at 2 hours postinjection, respectively. Scintigraphic images of tumor bearing mice using 131I, 99mTc, and 188Re allowed clear visualization of ARO-N tumors. In summary, NIS gene transfection to a single anaplastic thyroid cancer cell line efficiently triggered high tumor uptake of radioiodines, 99mTc and 188Re. These results demonstrate the possibility of imaging and therapy using NIS gene transfection in anaplastic thyroid carcinoma, although the short retention time is considered the major impediment to be resolved for the successful implementation.
Lee
Yong Jin
YJ
Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Chung
June-Key
JK
Shin
Jae Hoon
JH
Kang
Joo Hyun
JH
Jeong
Jae Min
JM
Lee
Dong Soo
DS
Lee
Myung Chul
MC
D000818:Animals; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011868:Radioisotopes / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D012211:Rhenium / Q000493:pharmacokinetics*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013667:Technetium / Q000493:pharmacokinetics*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D011868:Radioisotopes; D012211:Rhenium; D027981:Symporters; D013667:Technetium; D000099209:Sodium-Iodide Symporters