Noninvasive imaging for monitoring of viable cancer cells using a dual-imaging reporter gene.
Molecular imaging methods have been used recently to investigate biologic events. To develop a molecular imaging method suitable for monitoring viable cancer cells, we made a dual-imaging reporter gene system and examined the correlation between cancer cell number and signals from 2 reporter genes, sodium iodide symporter (NIS) and luciferase.


METHODS
NIS and luciferase genes were linked with the internal ribosomal entry site and transfected into SK-HEP1 cells to generate SK-HEP1-NL cells. (125)I uptake assays, luciferase assays, and scintigraphic and luminescence imaging were performed on SK-HEP1-NL cells. After treating with doxorubicin, cell counting, assays, and imaging were performed. SK-HEP1 and SK-HEP1-NL cells were inoculated subcutaneously into the flanks of nude mice. After incubation, scintigraphic and luminescence images were acquired and quantitated.


RESULTS
The results of radioiodide uptake, luciferase assay, and scintigraphic and luminescence imaging in vitro correlated well with viable cell numbers. Upon increasing the concentration of doxorubicin, cell numbers decreased, and this correlated with a decrease in radioactivity and luminescence intensity. The radioactivity from in vivo scintigraphic images and the intensity from luminescence images were also found to be proportional to the tumor weight.


CONCLUSIONS
The developed dual-reporter imaging method using NIS and the luciferase gene reflected viable cancer cell numbers and could detect changes in cell number after doxorubicin treatment.
Shin
Jae Hoon
JH
Department of Nuclear Medicine, Seoul National University Hospital, Seoul 110-744, Korea.
Chung
June-Key
JK
Kang
Joo Hyun
JH
Lee
Yong Jin
YJ
Kim
Kwang Il
KI
So
Young
Y
Jeong
Jae Min
JM
Lee
Dong Soo
DS
Lee
Myung Chul
MC
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D004317:Doxorubicin / Q000494:pharmacology*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008156:Luciferases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D027981:Symporters / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
D004317:Doxorubicin; D007457:Iodine Radioisotopes; D008156:Luciferases; D027981:Symporters; D000099209:Sodium-Iodide Symporters