Treatment of Breast Tumor Cells In Vitro with the Mitochondrial Membrane Potential Dissipater Valinomycin Increases 18F-FDG Incorporation

Timothy Andrew Davies Smith, Morgan Graeme Blaylock

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Mitochondrial membrane potential is essential for adenosine triphosphate (ATP) synthesis by oxidative phosphorylation, and its abolition is an early event during apoptosis, a type of cell death commonly exhibited by tumor cells responding to treatment. Dissipation of mitochondrial membrane potential can be specifically induced using the K+ ion channel-opening agent valinomycin and has been used in this study to determine how the loss of mitochondrial membrane potential could influence F-18-FDG incorporation. Methods: MCF-7 cells were treated with valinomycin for 30 min, inducing loss of mitochondrial membrane potential as determined using flow cytometry with the JC-1 probe. F-18-FDG incorporation, the initial rate of O-methyl-D-glucose incorporation (a measure of glucose transport), hexokinase activity and subcellular distribution, ATP content using bioluminescence, and lactate production were determined on control and valinomycin-treated cells. Results: A 30-min treatment of MCF-7 cells with 1 mu mol of valinomycin per liter resulted in absence of red fluorescence from JC-1, indicative of dissipation of mitochondrial membrane potential. 18F-FDG incorporation was significantly increased by 30 min of treatment with valinomycin and was still apparent after 3.5 h of incubation. Hexokinase activity and subcellular distribution were not significantly different between control cells and cells treated for 30 min with valinomycin. Glucose transport was moderately though significantly increased, and lactate production was also increased. Conclusion: Loss of mitochondrial membrane potential is associated with increased 18F-FDG incorporation, glucose transport, and lactate production.

Original languageEnglish
Pages (from-to)1308-1312
Number of pages5
JournalJournal of Nuclear Medicine
Volume48
Issue number8
DOIs
Publication statusPublished - Aug 2007

Keywords

  • F-18-FDG
  • mitochondria
  • membrane potential
  • glucose transport
  • lactate
  • glucose-metabolism
  • 2-fluoro-2-deoxy-D-glucose uptake
  • ionizing-radiation
  • intracellular PH
  • early response
  • radiotherapy
  • apoptosis
  • accumulation
  • chemotherapy
  • hexokinase

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