title: Influence of resistance to 5-fluorouracil and tomudex on [18F]‑FDG incorporation,             glucose transport and hexokinase activity.
abstract: Drug resistance is a major obstacle to cancer cure and may influence [18F]-fluorodeoxyglucose             (FDG) incorporation. In this study, glucose transport, hexokinase activity and             [18F]-FDG incorporation were measured in drug-resistant tumour cells generated             by exposing H630 colon and MCF7 breast cancer cells to increasing concentrations             of tomudex (raltitrexed) or 5-fluorouracil (5FU). Drug sensitivity was determined             using the XTT assay: Tomudex-resistant (H630TDX and MCF7TDX) cells were more than             40,000-fold less sensitive to tomudex than were the parental wild-type, H630WT             and MCF7WT cells, respectively. 5FU-resistant (H630R10) cells were 100-fold less             sensitive than parental H630WT cells to 5FU. As previously reported for 5FU-resistant             MCF7 breast cancer cells, [18F]-FDG incorporation was decreased in H630R10 colon             cancer cells compared to the parental line. By contrast, both tomudex-resistant             cell lines exhibited increased [18F]-FDG incorporation compared with the parental             lines. H630R10 and MCF7TDX cells exhibited higher rates of glucose transport,             measured as the initial rate of O-methyl-glucose (OMG) uptake, compared to wild-type             cells; however, glucose transport was not significantly different between H630TDX             cells and the parental cells. Hexokinase activity was lower in H630R10 and MCF7TDX             cells compared with sensitive parental cells but unchanged in H630TDX cells. In             conclusion, our results show that [18F]-FDG incorporation is influenced by resistance             to antifolate and fluoropyrimidine-based anti-cancer drugs in a drug-dependent             manner and the underlying mechanisms appear to be cell- and drug-dependent. Glucose             transport may be a useful marker of resistance to 5FU.
authors.affiliation: Division of Applied Medicine, College of Life Sciences and Medicine,                     University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Alison A
authors.initials: AA
authors.lastname: Law
authors.forename: Elaina S R
authors.initials: ES
authors.lastname: Collie-Duguid
authors.forename: Tim A D
authors.initials: TA
authors.lastname: Smith
mesh_terms: D019325:3-O-Methylglucose / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D011799:Quinazolines / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D019275:Radiopharmaceuticals; D013876:Thiophenes; D019788:Fluorodeoxyglucose F18; D019325:3-O-Methylglucose; D006593:Hexokinase; C068874:raltitrexed; D005947:Glucose; D005472:Fluorouracil