PET response evaluation to tyrosine kinase inhibitors in a GIST xenograft model

Objectives To assess treatment response to sunitinib and imatinib in a GIST xenograf model using a clinical PET scanner.

Methods A human GIST tumor with mutations in KIT exon 11 and 17, clinically resistant to imatinib, was implanted in nude mice. After 8 passages 33 mice were randomly allocated to three treatment groups and given imatinib, sunitinib or placebo for 8 days. FDG PET tumor-to-liver uptake ratios and tumor size were used as markers for treatment response.

Results The xenografts maintained the KIT mutations of the patient. Tumor volume in the control group increased by 11.5 % during the 8 days (p=0.27). 24 h after onset of therapy tumor volume in the imatinib and sunitinib groups were reduced by 15% (p=0.002) and 12% (p=0.03) respectively. At day 8 the volumes were reduced by 20% and 27%. No changes in tumor-to-liver ratio were found in the control tumors, whereas significantly decreased metabolic activity was seen in both treatment groups at day 1 and day 8 (suntinib; -55% and -50%, both p<0.001; imatinib; -41% and -35% both p<0.005). There were no significant differences between the imatinib and sunitinib groups.

Conclusions Significant treatment effects both by sunitinib and imatinib were observed. This supports maintaining treatment also in tumors apparently resistant to imatinib. Effects of novel targeted therapies can be evaluated in this xenograft model.