Effect of increase of radiation dose on local control relates to pre-treatment FDG uptake in FaDu tumours in nude mice.

Objectives: To investigate whether heterogeneity in [(18)F]2-fluoro-2-deoxy-d-glucose (FDG) uptake in a single tumour line, i.e. in tumours with identical genetic background, relates to radiation response.

Materials And Methods: Sixty-two human FaDu head and neck squamous cell carcinomas in nude mice with a diameter of 7mm entered the study. FDG-PET scanning was performed without anaesthesia on an animal PET scanner immediately prior to irradiation in order to determine maximum standardized uptake values (SUV(max)). Single dose irradiations of 25 or 35Gy were applied under normal blood flow conditions using 200kV X-rays (0.5mm Cu, approximately 1.2Gy min(-1)). The mice were observed for 120 days after irradiation, experimental endpoint was local tumour control evaluated using the Kaplan-Meier method.

Results: Analyzing all 62 animals, tumour control probability after irradiation with 25Gy was significantly lower than after irradiation with 35Gy (29% vs. 57%, log rank p=0.016). Pre-treatment SUV(max) values ranged from 0.72 to 3.47, the median SUV(max) value was 1.59. In tumours with FDG uptake less than the median SUV(max), local control was 37% after 25Gy vs. 47% after 35Gy (p=0.37). In contrast, substantial differences in local tumour control were found in tumours with FDG uptake above the median SUV(max) (24% vs. 71%, p=0.006). Multivariate Cox analysis revealed a significant decrease of hazard of recurrence with increasing dose and SUV(max).

Conclusions: An increase of radiation dose had a greater effect on local control in FaDu tumours with higher FDG uptake than in tumours with lower FDG uptake. This supports the hypothesis that pre-treatment FDG-PET may provide useful information for heterogeneous radiation dose prescription in subvolumes of tumours of individual patients. As only one tumour model was studied and single doses were applied, confirmatory investigations using further tumour models and fractionated radiotherapy are warranted.