In vivo long-term imaging and radioiodine therapy by sodium-iodide symporter gene expression using a lentiviral system containing ubiquitin C promoter.
To establish stable and long-term gene expression in vitro and in vivo, we developed a lentiviral vector system carrying sodium iodide symporter (hNIS) gene under UbC promoter, and transfected this into a colon cancer cell line. The in vitro and in vivo kinetics of radioiodine and [99mTc]-pertechnetate were then investigated, and the therapeutic effect of 1-131 was evaluated in this system. The hNIS gene was transferred into CT26 cells using lentivirus containing UbC promoter. In vitro iodide uptake and efflux were measured in CT26-hNIS cells at various time points. In addition, scintigraphic images were acquired at 30 min after injecting [99mTc]-pertechnetate i.p. into Balb/C mice for 27 days after CT26-hNIS induction. Biodistribution studies were performed at 10 and 30 min and at 1.5, 6 and 24 h after [99mTc]-pertechnetate injections, and the therapeutic effects of radioiodine were investigated by measuring tumor size using a caliper or by quantifying tumor radioactivity levels in scintigraphic images. The iodide uptakes of CT26-hNIS tumors were 10-fold greater than those of CT26 tumors. In addition, iodide uptake was completely blocked by 100 microM potassium perchlorate. The accumulation of [99mTc]-pertechnetate in hNIS expressing tumor cells was found to be positively related to tumor growth. In biodistribution studies, the %ID/g values of CT26-hNIS were 84.0 +/- 4.5 at 1.5 h and 40.8 +/- 3.9 at 24 h and these were approximately 60 times greater than those of CT26 at these time points. Tumor growth in mice treated with 131I was retarded until 46 days post-tumor challenge. The devised lentiviral vector system carrying hNIS controlled by UbC promoter was found to be suitable for the long-term monitoring and radionuclide therapy of cancer in living organism.
Kim
Hyun Joo
HJ
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jeon
Yong Hyun
YH
Kang
Joo Hyun
JH
Lee
Yong Jin
YJ
Kim
Kwang Il
KI
Chung
Hye Kyung
HK
Jeong
Jae Min
JM
Lee
Dong Soo
DS
Lee
Myung Chul
MC
Chung
June-Key
JK
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D011877:Radionuclide Imaging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters / Q000235:genetics*; D014018:Tissue Distribution; D025822:Ubiquitin C / Q000235:genetics*; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D025822:Ubiquitin C; D000099209:Sodium-Iodide Symporters