Feasibility of sodium/iodide symporter gene as a new imaging reporter gene: comparison with HSV1-tk.
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.
Shin
Jae Hoon
JH
Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Chongno-gu, Seoul, Korea.
Chung
June-Key
JK
Kang
Joo Hyun
JH
Lee
Yong Jin
YJ
Kim
Kwang Il
KI
Kim
Chul Woo
CW
Jeong
Jae Min
JM
Lee
Dong Soo
DS
Lee
Myung Chul
MC
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
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