title: Feasibility of sodium/iodide symporter gene as a new imaging reporter gene: comparison with HSV1-tk.
abstract: Positron emission tomography (PET) imaging reporter genes, such as HSV1-tk and D(2) receptor genes, make it possible to visualise gene expression non-invasively and repetitively in vivo. However, these systems require the synthesis of complicated substrates and the availability of expensive PET equipment. Expression of the sodium/iodide symporter ( NIS) gene can be easily monitored with radioiodines and technetium-99m using a gamma camera. To evaluate the possibility of using NIS as an imaging reporter gene, we compared its characteristics with those of the conventional HSV1-tk gene. The CM cell line was made by transfecting the HSV1-tk gene into CT-26 (mouse colon carcinoma cell line). The CTN and CMN cell lines were then made by transfecting the NIS gene into CT-26 and CM. We measured the uptake of iodine-125 iodovinyldeoxyuridine ([(125)I]IVDU) and (125)I to evaluate the expression of the HSV1-tk and NIS genes, respectively. Each cell line was injected into four flank sites in Balb/c mice. The biodistribution study was performed after intravenously injecting [(125)I]IVDU and (131)I, and (131)I scintigraphy was performed for the evaluation of NIS expression. In vitro studies indicated that CTN and CMN had 40- to 79-fold and 150- to 256-fold higher uptake of (125)I than CT-26 and CM, respectively. Furthermore, CM and CMN showed 57- to 69-fold higher uptake of [(125)I]IVDU than CT-26 and CTN. NIS gene expression and (125)I accumulation were found to be directly correlated ( R(2)=0.923), as were HSV1-tk gene expression and [(125)I]IVDU accumulation ( R(2)=0.956). Calculated signal per unit NIS and HSV1-tk mRNA expression was 23,240+/-3,755 cpm and 34,039+/-5,346 cpm, respectively. In vivo study indicated that CTN and CMN had 2.3- and 5.8-fold higher uptake of (131)I than CT-26 and CM, and 1.8- and 3.5-fold higher uptake of [(125)I]IVDU than CT-26 and CTN. Scintigraphy using (131)I easily visualised CTN and CMN tumours. In conclusion, the NIS gene may be viewed as an imaging reporter gene with comparable performance to the HSV1-tk gene for monitoring target gene expression.
authors.affiliation: Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Chongno-gu, Seoul, Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Shin
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
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: Chul Woo
authors.initials: CW
authors.lastname: Kim
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
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D005240:Feasibility Studies; D020869:Gene Expression Profiling / Q000379:methods*; D017930:Genes, Reporter / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D051379:Mice; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods; D000099209:Sodium-Iodide Symporters
chemical_list: D014408:Biomarkers, Tumor; D007065:Idoxuridine; D019275:Radiopharmaceuticals; D027981:Symporters; D013937:Thymidine Kinase; D000099209:Sodium-Iodide Symporters; C030360:5-(2-iodovinyl)-2'-deoxyuridine; C092717:thymidine kinase 1