title: In vivo long-term imaging and radioiodine therapy by sodium-iodide symporter gene expression using a lentiviral system containing ubiquitin C promoter.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Jeon
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Kang
authors.forename: Yong Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kwang Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Chung
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
mesh_terms: 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
chemical_list: D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D025822:Ubiquitin C; D000099209:Sodium-Iodide Symporters