18F-FLT and 18F-FDG PET to measure response to radiotherapy combined with celecoxib in two colorectal xenograft models.
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.
Debucquoy
Annelies
A
Lab of Experimental Radiotherapy, Department of Radiation Oncology and Experimental Therapy, University Hospitals Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. annelies.debucquoy@med.kuleuven.be
Devos
Ellen
E
Vermaelen
Peter
P
Landuyt
Willy
W
De Weer
Stefanie
S
Van Den Heuvel
Frank
F
Haustermans
Karin
K
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
D052246:Cyclooxygenase 2 Inhibitors; D015224:Dideoxynucleosides; D011720:Pyrazoles; D013449:Sulfonamides; D019788:Fluorodeoxyglucose F18; D051546:Cyclooxygenase 2; D000068579:Celecoxib; C002854:alovudine