Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: In vitro evaluation for PET imaging

Heikki Minn, Anaira C. Clavo, Richard L. Wahl

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)941-946
Number of pages6
JournalNuclear Medicine and Biology
Volume23
Issue number8
DOIs
StatePublished - Nov 1996
Externally publishedYes

Keywords

  • fluorodeoxyglucose
  • hypoxia
  • leucine
  • methionine
  • positron emission tomography
  • squamous-cell carcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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