PMID- 17998098 OWN - NLM STAT- MEDLINE DCOM- 20080306 LR - 20161124 IS - 0969-8051 (Print) IS - 0969-8051 (Linking) VI - 34 IP - 8 DP - 2007 Nov TI - Decreased [18F]fluoro-2-deoxy-d-glucose incorporation and increased glucose transport are associated with resistance to 5FU in MCF7 cells in vitro. PG - 955-60 AB - INTRODUCTION: Tumor refractoriness to chemotherapy is frequently due to the acquisition of resistance. Resistant cells selected by exposure to chemotherapy agents may exhibit differences in [18F]fluoro-2-deoxy-d-glucose (FDG) incorporation, as compared with sensitive cells. METHODS: FDG incorporation, hexokinase (HK) activity, glucose transport and ATP content were determined in clones of 5-fluorouracil (5FU)-resistant MCF7 cells, established by long-term exposure to increasing 5FU concentrations, and in parental MCF7 cells. RESULTS: FDG incorporation was decreased in MCF7 cells resistant to 5FU; HK activity was similar in the resistant and sensitive cells, while glucose transport was increased, as compared with sensitive cells. Treatment of cells with the glucose efflux inhibitor phloretin increased FDG incorporation to similar levels in the resistant and sensitive cells. Analysis of microarray data demonstrated the expression of GLUT1, 8 and 10 transporters in MCF7 cells. GLUT8 and 10 expression was decreased in the resistant cells, while GLUT1 was only increased in cells resistant to the lowest 5FU concentration. CONCLUSION: FDG incorporation in 5FU-resistant MCF7 cells is decreased, as compared with sensitive cells. Our findings also suggest that this may be due to high rates of membrane glucose transport in the resistant cells resulting in enhanced efflux of FDG. We believe that this is the first demonstration that facilitative glucose transporters can actually decrease the incorporation of FDG. FAU - Smith, Tim A D AU - Smith TA AD - PET Unit, Department of Biomedical Physics, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. t.smith@biomed.abdn.ac.uk FAU - Sharma, Rituka I AU - Sharma RI FAU - Wang, Weiguang G AU - Wang WG FAU - Welch, Andy E AU - Welch AE FAU - Schweiger, Lutz F AU - Schweiger LF FAU - Collie-Duguid, Elaina S R AU - Collie-Duguid ES LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070919 PL - United States TA - Nucl Med Biol JT - Nuclear medicine and biology JID - 9304420 RN - 0 (Radiopharmaceuticals) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) RN - IY9XDZ35W2 (Glucose) RN - U3P01618RT (Fluorouracil) SB - IM MH - Biological Transport, Active/drug effects MH - Breast Neoplasms/*diagnostic imaging/*metabolism MH - Cell Line, Tumor MH - *Drug Resistance, Neoplasm MH - Fluorodeoxyglucose F18/*pharmacokinetics MH - Fluorouracil/*administration & dosage MH - Glucose/*metabolism MH - Humans MH - Metabolic Clearance Rate/drug effects MH - Radionuclide Imaging MH - Radiopharmaceuticals/pharmacokinetics EDAT- 2007/11/14 09:00 MHDA- 2008/03/07 09:00 CRDT- 2007/11/14 09:00 PHST- 2007/06/29 00:00 [received] PHST- 2007/07/10 00:00 [revised] PHST- 2007/07/12 00:00 [accepted] PHST- 2007/11/14 09:00 [pubmed] PHST- 2008/03/07 09:00 [medline] PHST- 2007/11/14 09:00 [entrez] AID - S0969-8051(07)00187-4 [pii] AID - 10.1016/j.nucmedbio.2007.07.007 [doi] PST - ppublish SO - Nucl Med Biol. 2007 Nov;34(8):955-60. doi: 10.1016/j.nucmedbio.2007.07.007. Epub 2007 Sep 19.