TY - JOUR
T1 - Effect of nitroimidazole sensitizers on in vitro glycolytic metabolism of hypoxic squamous cell carcinoma
AU - Minn, Heikki
AU - Clavo, Anaira C.
AU - Fisher, Susan J.
AU - Wahl, Richard L.
N1 - Funding Information:
The authors thank Dr Reidar Grénman, Department of Otolaryngology, University of Turku, for establishing the cell line used in the study. Dr Peter F. Sorter of Hoffmann-La Roche Inc., Nutley, NJ, USA and Dr A. Rossetti of Farmitalia Carlo Erba, Milan, Italy are thanked for donating the two nitroimidazole compounds, misonidazole and nimorazole, respectively, used in this study. This investigation was supported by grants CA 52880, CA 53172, and CA56731 from the National Cancer Institute, and by grant 8001694 from the Academy of Finland.
PY - 2000
Y1 - 2000
N2 - Two nitroimidazole compounds, misonidazole (MISO) and nimorazole (NIMO), were evaluated for their potential to modify uptake of [5,6-3H] 2-fluoro-2- deoxy-D-glucose (3H-FDG) in the human squamous carcinoma cell line UT-SCC-5 exposed to increasing levels of hypoxia. UT-SCC-5 cells were incubated with 0-10 mM of MISO or NIMO under normal or reduced oxygen concentrations of 20%, 1.5%, or 0% with 5% CO2 for 6 h, after which 74 KBq of 3H-FDG was added in media for 1 h. In the presence of normal concentrations of O2, both sensitizers increased 3H-FDG uptake by up to 178% (MISO) or 84% (NIMO) when compared with untreated cells. In anoxia, MISO decreased 3H-FDG uptake to 35% of that of control whereas NIMO-treated cells showed a respective decrease in tracer uptake to 62%. Clonogenic assays clearly indicated that MISO was toxic and NIMO moderately toxic for hypoxic cells, whereas both sensitizers exerted only a very modest effect on survival of fully oxygenated cells. Our findings indicate that nitroimidazole treatment consistently increases 3H-FDG uptake into UT-SCC-5 cells under normal oxygen concentrations. In hypoxia, the observed decrease in tracer uptake is dependent on both the level of ambient oxygen and drug concentration and may reflect both direct toxicity and inhibition of glycolysis. The observations may be useful for further applications of 18F-FDG positron emission tomography (PET) to monitor effects of hypoxic cell radiosensitizers on tumor metabolism in vivo.
AB - Two nitroimidazole compounds, misonidazole (MISO) and nimorazole (NIMO), were evaluated for their potential to modify uptake of [5,6-3H] 2-fluoro-2- deoxy-D-glucose (3H-FDG) in the human squamous carcinoma cell line UT-SCC-5 exposed to increasing levels of hypoxia. UT-SCC-5 cells were incubated with 0-10 mM of MISO or NIMO under normal or reduced oxygen concentrations of 20%, 1.5%, or 0% with 5% CO2 for 6 h, after which 74 KBq of 3H-FDG was added in media for 1 h. In the presence of normal concentrations of O2, both sensitizers increased 3H-FDG uptake by up to 178% (MISO) or 84% (NIMO) when compared with untreated cells. In anoxia, MISO decreased 3H-FDG uptake to 35% of that of control whereas NIMO-treated cells showed a respective decrease in tracer uptake to 62%. Clonogenic assays clearly indicated that MISO was toxic and NIMO moderately toxic for hypoxic cells, whereas both sensitizers exerted only a very modest effect on survival of fully oxygenated cells. Our findings indicate that nitroimidazole treatment consistently increases 3H-FDG uptake into UT-SCC-5 cells under normal oxygen concentrations. In hypoxia, the observed decrease in tracer uptake is dependent on both the level of ambient oxygen and drug concentration and may reflect both direct toxicity and inhibition of glycolysis. The observations may be useful for further applications of 18F-FDG positron emission tomography (PET) to monitor effects of hypoxic cell radiosensitizers on tumor metabolism in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0034107136&partnerID=8YFLogxK
U2 - 10.1080/028418600430770
DO - 10.1080/028418600430770
M3 - Article
C2 - 10859011
AN - SCOPUS:0034107136
SN - 0284-186X
VL - 39
SP - 199
EP - 205
JO - Acta Oncologica
JF - Acta Oncologica
IS - 2
ER -