Effect of nitroimidazole sensitizers on in vitro glycolytic metabolism of hypoxic squamous cell carcinoma

Two nitroimidazole compounds, misonidazole (MISO) and nimorazole (NIMO), we re evaluated for their potential to modify uptake of [5,6-H-3] 2-fluoro-2-d eoxy-D-glucose (H-3-FDG) in the human squamous carcinoma cell line UT-SCC-5 exposed to increasing levels of hypoxia. UT-SCC-5 cells were incubated wit h 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 H-3-FDG was add ed in media for 1 h. In the presence of normal concentrations of O-2, both sensitizers increased H-3-FDG uptake by up to 178% (MISO) or 84% (NIMO) whe n compared with untreated cells. In anoxia, MISO decreased H-3-FDG uptake t o 35% of that of control whereas NIMO-treated cells showed a respective dec rease in tracer uptake to 62%. Clonogenic assays clearly indicated that MIS O was toxic and NIMO moderately toxic for hypoxic cells, whereas both sensi tizers exerted only a very modest effect on survival of fully oxygenated ce lls. Our findings indicate that nitroimidazole treatment consistently incre ases H-3-FDG uptake into UT-SCC-5 cells under normal oxygen concentrations. In hypoxia, the observed decrease in tracer uptake is dependent on both th e level of ambient oxygen and drug concentration and may reflect both direc t toxicity and inhibition of glycolysis. The observations may be useful for further applications of F-18-FDG positron emission tomography (PET) to mon itor effects of hypoxic cell radiosensitizers on tumor metabolism in vivo.