TY - JOUR T1 - Treatment of Breast Tumor Cells In Vitro with the Mitochondrial Membrane Potential Dissipater Valinomycin Increases <sup>18</sup>F-FDG Incorporation JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1308 LP - 1312 DO - 10.2967/jnumed.107.041665 VL - 48 IS - 8 AU - Tim A.D. Smith AU - Morgan G. Blaylock Y1 - 2007/08/01 UR - http://jnm.snmjournals.org/content/48/8/1308.abstract N2 - 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 18F-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. 18F-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 μmol 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. ER -