Noninvasive bioluminescent and microPET imaging for the regulation of NF-kappaB in human hepatoma-bearing mice.
The activity of nuclear factor-kappaB (NF-kappaB), a nuclear transcription factor, influences both critical tumor promotion and host-tumor interactions. Preventing NF-kappaB activation may thus inhibit the development of cancer. Therefore, development of easy and rapid methods to evaluate the regulation of NF-kappaB is needed for drug discovery. The aim of this study was to visualize the regulation of NF-kappaB by real-time, noninvasive bioluminescence and microPET imaging in vivo.


METHODS
A highly responsive HepG2/NF-kappaB/luc clone L for 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion inhibited by methotrexate (MTX) was selected by high-throughput bioluminescent imaging (BLI) in vitro. BLI and microPET using (18)F-fluorodeoxyglucose (FDG) imaging were performed in HepG2/NF-kappaB/Luc/L hepatoma-bearing SCID mice.


RESULTS
The luciferase expression by BLI assay reflected that the TPA-induced NF-kappaB activity was suppressed by MTX after 16 h treatment. A positive correlation between in vitro and in vivo MTX-suppressed TPA-induced NF-kappaB activity was indicated. MicroPET imaging could not demonstrate any decrease in FDG uptake during the early stage at 24 h after TPA and MTX treatment.


CONCLUSIONS
BLI directly revealed that MTX inhibited cellular transformation by suppressing NF-kappaB activity. Molecular imaging would accelerate the validation of the gene regulation of tumor cells in preclinical cellular and mouse models.
Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan 325, Taiwan, Republic of China.
Tsui-Jung
TJ
Chang
Ya-Jen
YJ
Chang
Tin-Yun
TY
Ho
Chien-Yun
CY
Hsiang
Chia-Yu
CY
Yu
Te-Wei
TW
Lee
Wu-Jyh
WJ
Lin
Chih-Hsien
CH
Chang
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D003952:Diagnostic Imaging; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D002273:Carcinogens; D016328:NF-kappa B; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate; D008727:Methotrexate