INFLUENCE OF HYPOXIA ON TRACER ACCUMULATION IN SQUAMOUS-CELL CARCINOMA - IN-VITRO EVALUATION FOR PET IMAGING

Hypoxic accumulation of 2-[5,6-H-3]fluoro-2-deoxy-D-glucose ([H-3]FDG) ,L-[methyl- H-3]methionine ([H-3]MET), and L-[1-H-3]leucine ([H-3]LEU) was evaluated in two cell lines (UT-SCC-5 and UT-SCC-20) obtained fro m patients with squamous-cell carcinoma of the head and neck, Both cel l lines mere exposed to decreasing oxygen atmosphere (20%, 1.5%, or 0% O-2) for 6 h, after which they were incubated for a further 1 h with tritiated FDG, MET, or LEU. An anoxic atmosphere resulted in a mean in crease of [H-3]FDG uptake of 120% and 46% over a baseline 20% oxygen a tmosphere for UT-SCC-5 and UT-SCC 20A, respectively. Both total and ac id-precipitable [H-3]MET uptake remained unchanged at 0% versus baseli ne, whereas acid-precipitable [H-3]LEU uptake decreased by 46% for UT- SCC-5 and by 34% for UT-SCC 20A at 0% O-2. Our findings demonstrate th at [H-3]FDG accumulation is increased in hypoxic UT-SCC cell lines pro bably through activation of the metabolic steps associated with the gl ycolytic pathway. The decrease in acid-precipitable [H-3]LEU uptake in hypoxia may indicate a decline in protein synthesis, whereas the unch anged [H-3]MET uptake probably reflects the unaffected amino acid tran sport and slow incorporation of radiolabeled methyl group of MET in tu mor proteins and nucleic acids. FDG and LEU, but probably not MET, war rant additional study as hypoxia-avid or hypoxia-reduced tracers for a ssessment of treatment effects designed to modify hypoxia. Copyright ( C) 1996 Elsevier Science Inc.