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.
Chang
Tsui-Jung
TJ
Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan 325, Taiwan, Republic of China.
Chang
Ya-Jen
YJ
Ho
Tin-Yun
TY
Hsiang
Chien-Yun
CY
Yu
Chia-Yu
CY
Lee
Te-Wei
TW
Lin
Wu-Jyh
WJ
Chang
Chih-Hsien
CH
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