Determination of 2-fluoro-2-deoxy-d-glucose uptake and ATP level for evaluating drug effects in neoplastic cells

Abstract

The glucose analogue 2-fluoro-2-deoxy-D-glucose (FDG) was used to study chemosensitivity of two human ovarian cancer cell lines and of murine L1210 cells. Cell viability was determined by measuring intracellular adenosine triphosphate (ATP) with a bioluminescence method, which has been shown to correlate closely with trypan blue, stem cell, and [3H]TdR assays. All three cell lines were sensitive to cytostatic drugs, which exerted a parallel decrease in the intracellular FDG and ATP levels. The two measures correlated positively (r = 0.66, P less than 0.001), indicating that FDG uptake is closely linked with ATP production. Relatively low hexokinase (HK)-to-glucose 6-phosphatase (HK/G6-Pase) ratios were measured, which suggests that the metabolic trapping of FDG 6-phosphate within the cytosol is incomplete. Apparently, these cell lines may not depend exclusively on glycolysis for their energy requirement. We conclude that cell killing caused by cytostatic drugs is associated with a decreased ATP content and FDG uptake. This indicates that not only ATP but also FDG may be used to study drug effects in vitro.

Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer

“…Measurement of FDG uptake in tumors may not only assist in oncologic imaging, but can also be useful in the evaluation of the treatment effect of anti-glycolytic agents [23]. Several studies showed that FDG may be used to study drug effects in vitro [24,25]. Our study further validated this principle in vivo, by showing lesser FDG uptake after 3-BrPA treatment, which was specific for tumor tissue.…”

The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression

“…Interestingly, it has been shown that the killing of neoplastic cells by cytostatic drugs is associated with decreased ATP content and FDG uptake. This indicates that FDG uptake is closely linked with ATP production and that not only ATP but also FDG could be used to study drug effects in vitro [ 51 ].…”

[18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study

“…Several studies have demonstrated the ability of functional imaging techniques to detect subclinical alterations in tumour physiology and biochemistry resulting from efficacious therapy [1,6,13,15,18,20]. These alterations may occur long before a morphologic change in the tumour mass is apparent.…”