¹⁸F-FLT and ¹⁸F-FDG PET to measure response to radiotherapy combined with celecoxib in two colorectal xenograft models

Abstract

Purpose: To determine the dependence of celecoxib on the tumour micro-environment in vitro and in vivo and to compare the use of ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) and ¹⁸F- 3′-deoxy-3-fluorothymidine (¹⁸F-FLT) to measure tumour response.

Materials and 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 ¹⁸F-FDG and ¹⁸F-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 ¹⁸F-FDG and ¹⁸F-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. ¹⁸F-FLT seems a good alternative for ¹⁸F-FDG to follow tumour growth after radiation treatment.

Keywords:

• In vivo PET
• COX-2
• colorectal carcinoma cells
• imaging
• radiosensitizers
• xenografts