Table of Contents
International Journal of Molecular Imaging
Volume 2011 (2011), Article ID 874585, 8 pages
http://dx.doi.org/10.1155/2011/874585
Research Article

[ 𝟏 𝟖 F ]Fluoro-2-Deoxy-D-Glucose Incorporation by MCF-7 Breast Tumour Cells In Vitro Is Modulated by Treatment with Tamoxifen, Doxorubicin, and Docetaxel: Relationship to Chemotherapy-Induced Changes in ATP Content, Hexokinase Activity, and Glucose Transport

1School of Medical Sciences (Biomedical Physics), Aberdeen Biomedical Imaging Centre (ABIC), University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
2John Mallard PET Centre, Aberdeen Biomedical Imaging Centre (ABIC), University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK

Received 15 July 2010; Revised 30 August 2010; Accepted 24 September 2010

Academic Editor: Adriaan Anthonius Lammertsma

Copyright © 2011 R. I. Sharma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Breast tumours responding to chemotherapy exhibit decreased [ 1 8 F ]fluoro-2-deoxy-D-glucose ([ 1 8 F ]FDG) incorporation. Underlying mechanisms of these changes is poorly understood. Here, in MCF-7 cells, responding to chemotherapy drugs commonly utilised in the treatment of breast cancer, [ 1 8 F ]FDG incorporation and several pivotal factors associated with [ 1 8 F ]FDG incorporation investigated. Methods. IC50 and subclinical doxorubicin, docetaxel, and tamoxifen doses determined using MTT assay. [ 1 8 F ]FDG incorporation by cells treated with IC50 drug doses for 48 hours and 72 hours were determined and FDG dephosphorylation estimated by measuring loss of 18F from [ 1 8 F ]FDG-preincubated cells (pulse-chase). Glucose transport determined by measuring initial uptake rate of non-metabolised glucose analogue omethylglucose; hexokinase activity and ATP content measured in cell homogenates; Cell cycle distribution determined using flow cytometry of propidium iodide stained nuclei. Results. [ 1 8 F ]FDG incorporation and ATP content decreased in cells after 72 hours treatment with IC50 doses of tamoxifen, doxorubicin, and docetaxel compared with untreated controls. Decreased glucose transport and/or hexokinase activity accompanied decreased [ 1 8 F ]FDG incorporation by MCF-7 cells treated with tamoxifen or doxorubicin but not docetaxel. Conclusions. Tumour cell [ 1 8 F ]FDG incorporation along with ATP content decreased by treatment with tamoxifen, doxorubicin and docetaxel paralleling clinical observations for solid tumours. Effect of each treatment on glucose transport and hexokinase activity was chemotherapy-drug dependent.