title: Colorectal tumor cells treated with 5-FU, oxaliplatin, irinotecan, and cetuximab exhibit changes in 18F-FDG incorporation corresponding to hexokinase activity and glucose transport.
abstract: The purpose of this study was to determine therapy-induced changes in 18F-FDG incorporation at the colorectal tumor cell level in response to conventional and novel chemotherapy agents and examine how these changes relate to factors involved in 18F-FDG incorporation.
  
  
  METHODS
  SW620 cells were treated with inhibitory concentration of 50% (IC50) doses (determined by MTT) of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan; HCT-8 cells were treated with IC50 doses of irinotecan, cetuximab, and irinotecan plus cetuximab. 18F-FDG incorporation, glucose transport, hexokinase (HK) activity, adenosine triphosphate (ATP) content, annexin V binding, and cell cycle distribution were determined after 24-, 48-, and 72-h treatments. Eight-hour treatments with and without subsequent incubation in drug-free medium were also examined. A clonogenic assay was used to determine the tumor-forming ability of treated cells.
  
  
  RESULTS
  Apoptosis was evident in SW620 cells, especially after treatment with irinotecan and 5-FU. 18F-FDG incorporation was increased in SW620 cells after 24- or 48-h treatments with some agents and in HCT-8 cells after irinotecan treatment but was decreased in all 72-h treatments or cell-line combinations including cetuximab. Treatment of SW620 cells for 8 h followed by 64 h in drug-free medium also resulted in decreased 18F-FDG incorporation. Decreased 18F-FDG incorporation broadly corresponded to glucose transport in HCT-8 cells and to HK activity in SW620 cells. Inhibition of glucose transport decreased 18F-FDG incorporation into HCT-8 but not into SW620 cells. ATP levels were decreased by oxaliplatin treatment and increased at 48 or 72 h after irinotecan treatment.
  
  
  CONCLUSIONS
  18F-FDG incorporation is modulated by therapy-induced changes in both glucose transport and HK activity depending on the tumor cell. Colorectal cells treated with IC50 doses of cetuximab also exhibit decreased 18F-FDG.
authors.affiliation: School of Medical Sciences (Biomedical Physics), University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
authors.forename: Rituka I
authors.initials: RI
authors.lastname: Sharma
authors.forename: Tim A D
authors.initials: TA
authors.lastname: Smith
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab; D015179:Colorectal Neoplasms; D004347:Drug Interactions; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D000077146:Irinotecan; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D019275:Radiopharmaceuticals / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D019275:Radiopharmaceuticals; D000077150:Oxaliplatin; D019788:Fluorodeoxyglucose F18; D000077146:Irinotecan; D006593:Hexokinase; D005947:Glucose; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin