title: 18F-FLT and 18F-FDG PET to measure response to radiotherapy combined with celecoxib in two colorectal xenograft models.
abstract: OBJECTIVE
  To determine the dependence of celecoxib on the tumour micro-environment in vitro and in vivo and to compare the use of (18)F-Fluorodeoxyglucose ((18)F-FDG) and (18)F- 3'-deoxy-3-fluorothymidine ((18)F-FLT) to measure tumour response.
  
  
  METHODS
  In vitro, colony assays were performed on a cyclo-oxygenase 2 (COX-2) negative (HCT116) and a COX-2 positive cell line (HCA7). Xenograft models of these cell lines were treated with celecoxib and/or radiotherapy. Micro Positron Emission Tomography (microPET) scans with (18)F-FDG and (18)F-FLT were performed at different time-points.
  
  
  RESULTS
  In vitro, no radiosensitising effect was seen in either of the cell lines. In vivo results showed a significant effect of celecoxib in the COX-2 negative tumours (HCT116) (enhancement ratio 1.5, p = 0.02) while no significant effect was observed in the COX-2 positive model (HCA7). A good correlation between (18)F-FDG and (18)F-FLT uptake was seen in both tumour models (r = 0.48, p = 0.002; r = 0.41, p = 0.005). After irradiation, a decrease in the uptake of both tracers was observed in both tumour models, which was more pronounced in the combination group, confirming the growth delay data.
  
  
  CONCLUSIONS
  The contradicting in vitro and in vivo results suggest a major role of the tumour micro-environment. (18)F-FLT seems a good alternative for (18)F-FDG to follow tumour growth after radiation treatment.
authors.affiliation: Lab of Experimental Radiotherapy, Department of Radiation Oncology and Experimental Therapy, University Hospitals Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. annelies.debucquoy@med.kuleuven.be
authors.forename: Annelies
authors.initials: A
authors.lastname: Debucquoy
authors.forename: Ellen
authors.initials: E
authors.lastname: Devos
authors.forename: Peter
authors.initials: P
authors.lastname: Vermaelen
authors.forename: Willy
authors.initials: W
authors.lastname: Landuyt
authors.forename: Stefanie
authors.initials: S
authors.lastname: De Weer
authors.forename: Frank
authors.initials: F
authors.lastname: Van Den Heuvel
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
mesh_terms: D000818:Animals; D000068579:Celecoxib; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015224:Dideoxynucleosides; D005260:Female; D019788:Fluorodeoxyglucose F18; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D015224:Dideoxynucleosides; D011720:Pyrazoles; D013449:Sulfonamides; D019788:Fluorodeoxyglucose F18; D051546:Cyclooxygenase 2; D000068579:Celecoxib; C002854:alovudine