TY - JOUR
T1 - Influence of hypoxia on tracer accumulation in squamous-cell carcinoma
T2 - In vitro evaluation for PET imaging
AU - Minn, Heikki
AU - Clavo, Anaira C.
AU - Wahl, Richard L.
N1 - Funding Information:
This studyw as supportedin part by grantsC A 52880, CA 53 172, and CA 56731 from the National Cancer Institute, USA, and by grant 8001694 from theA cademy of Finland. Dr. Reidm Gr&nan, MD, is cordially acknowledgefdo r establishing and donating the two cell lines used in the study. Dr. Sirkku Leskinen, MD, is thanked for valuable discussions on methionine metabolism.
PY - 1996/11
Y1 - 1996/11
N2 - Hypoxic accumulation of 2-[5,6-3H]fluoro-2-deoxy-D-glucose ([3H]FDG), L-[methyl-3H]methionine ([3H]MET), and L-[1-3H]leucine ([3H]LEU) was evaluated in two cell lines (UT-SCC-5 and UT-SCC-20) obtained from patients with squamous-cell carcinoma of the head and neck. Both cell lines were exposed to decreasing oxygen atmosphere (20%, 1.5%, or 0% O2) 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 increase of [3H]FDG uptake of 120% and 46% over a baseline 20% oxygen atmosphere for UT-SCC-5 and UT-SCC-20A, respectively. Both total and acid-precipitable [3H]MET uptake remained unchanged at 0% versus baseline, whereas acid-precipitable [3H]LEU uptake decreased by 46% for UT-SCC-5 and by 34% for UT-SCC-20A at 0% O2. Our findings demonstrate that [3H]FDG accumulation is increased in hypoxic UT-SCC cell lines probably through activation of the metabolic steps associated with the glycolytic pathway. The decrease in acid-precipitable [3H]LEU uptake in hypoxia may indicate a decline in protein synthesis, whereas the unchanged [3H]MET uptake probably reflects the unaffected amino acid transport and slow incorporation of radiolabeled methyl group of MET in tumor proteins and nucleic acids. FDG and LEU, but probably not MET, warrant additional study as hypoxia-avid or hypoxia-reduced tracers for assessment of treatment effects designed to modify hypoxia.
AB - Hypoxic accumulation of 2-[5,6-3H]fluoro-2-deoxy-D-glucose ([3H]FDG), L-[methyl-3H]methionine ([3H]MET), and L-[1-3H]leucine ([3H]LEU) was evaluated in two cell lines (UT-SCC-5 and UT-SCC-20) obtained from patients with squamous-cell carcinoma of the head and neck. Both cell lines were exposed to decreasing oxygen atmosphere (20%, 1.5%, or 0% O2) 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 increase of [3H]FDG uptake of 120% and 46% over a baseline 20% oxygen atmosphere for UT-SCC-5 and UT-SCC-20A, respectively. Both total and acid-precipitable [3H]MET uptake remained unchanged at 0% versus baseline, whereas acid-precipitable [3H]LEU uptake decreased by 46% for UT-SCC-5 and by 34% for UT-SCC-20A at 0% O2. Our findings demonstrate that [3H]FDG accumulation is increased in hypoxic UT-SCC cell lines probably through activation of the metabolic steps associated with the glycolytic pathway. The decrease in acid-precipitable [3H]LEU uptake in hypoxia may indicate a decline in protein synthesis, whereas the unchanged [3H]MET uptake probably reflects the unaffected amino acid transport and slow incorporation of radiolabeled methyl group of MET in tumor proteins and nucleic acids. FDG and LEU, but probably not MET, warrant additional study as hypoxia-avid or hypoxia-reduced tracers for assessment of treatment effects designed to modify hypoxia.
KW - fluorodeoxyglucose
KW - hypoxia
KW - leucine
KW - methionine
KW - positron emission tomography
KW - squamous-cell carcinoma
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U2 - 10.1016/S0969-8051(96)00134-5
DO - 10.1016/S0969-8051(96)00134-5
M3 - Article
C2 - 9004282
AN - SCOPUS:0030294855
SN - 0969-8051
VL - 23
SP - 941
EP - 946
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 8
ER -