RT Journal Article
SR Electronic
T1 Establishment of a Human Hepatocellular Carcinoma Cell Line Highly Expressing Sodium Iodide Symporter for Radionuclide Gene Therapy
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1571
OP 1576
VO 45
IS 9
A1 Joo Hyun Kang
A1 June-Key Chung
A1 Yong Jin Lee
A1 Jae Hoon Shin
A1 Jae Min Jeong
A1 Dong Soo Lee
A1 Myung Chul Lee
YR 2004
UL http://jnm.snmjournals.org/content/45/9/1571.abstract
AB To evaluate the possibility of radionuclide gene therapy and imaging in hepatocellular carcinoma cancer, we investigated the iodine accumulation of a human hepatocellular carcinoma cell line, SK-Hep1, by transfer of human sodium iodide symporter (hNIS) gene. By targeting NIS expression in SK-Hep1, we could also investigate whether these cells concentrate 99mTc-pertechnetate and 188Re-perrhenate as well as 125I in vitro and in vivo. Methods: The hNIS gene was transfected to human hepatocellular carcinoma SK-Hep1 cell lines using lipofectamine plus reagent. The uptake and efflux of 125I, 99mTc-pertechnetate, and 188Re-perrhenate were measured in the transfected and parental cells. Biodistribution was studied in nude mice bearing SK-Hep1 and SK-Hep1-NIS at 10 and 30 min and at 1, 2, 6, 16, and 23 h after injection of 125I, 99mTc- pertechnetate, or 188Re-perrhenate. In tumor imaging studies, the nude mice were intravenously injected with 188Re-perrhenate and imaged with a γ-camera equipped with a pinhole collimator at 30 and 60 min after injection. The survival rate (%) was determined by the clonogenic assay after 37 MBq/10 mL (1 mCi/10 mL) 131I and 188Re-perrhenate treatment. Results: SK-Hep1-NIS, stably expressing the NIS gene, accumulated 125I up 150 times higher than that of SK-Hep1. Iodine uptake of SK-Hep1-NIS is completely blocked by perchlorate. NIS gene transfection into SK-Hep1 also resulted in 112- and 87-fold increases of 99mTc-pertechnetate and 188Re-perrhenate uptake, respectively. Iodide efflux from SK-Hep1-NIS was relatively slow, with only 10% released during the initial 5 min, and 60% remained at 25 min. In the biodistribution study using SK-Hep1-NIS–xenographed mice, the tumor uptake of 125I, 188Re-perrhenate, and 99mTc-pertechnetate was 68.0 ± 15.0, 46.2 ± 9.1, and 59.6 ± 16.2 %ID/g (percentage injected dose per gram) at 2 h after injection, respectively. After 188Re-perrhenate injection in SK-Hep1 and SK-Hep1-NIS–xenographed nude mice, whole-body images clearly visualized the SK-Hep1-NIS tumor, whereas the control tumor was not visualized. The survival rate (%) of SK-Hep1-NIS was markedly reduced to 46.3% ± 10.1% and 28.9% ± 5.2% after 37 MBq/mL (1 mCi/10 mL) 131I and 188Re-perrhenate treatment compared with the survival rates of the parental cells. These results demonstrated that SK-Hep1-NIS could be selectively killed by the induced 131I and 188Re-perrhenate accumulation through NIS gene expression. Conclusion: NIS-based gene therapy using β-emitting radionuclides has the potential to be used in hepatocellular carcinoma management.