Preclinical evaluation of combined treatments in xenograft model of gastrointestinal stromal tumors (GISTs) using small animal PET

e20502 Background: Primary and secondary drug resistance to imatinib and sunitinib in the treatment of patients with GISTs has led a progressively growing urgency to develop new strategies such as drug combinations. Most GISTs are caused by mutations in the KIT receptor, leading to upregulated KIT tyrosine kinase activity. Imatinib (I) and nilotinib (N) directly inhibit the kinase activity of KIT, RAD001(Everolimus)(E) inhibits mTOR. We report a preclinical study on combinations of drugs in xenograft model of GIST in which effects were assessed with tumor dimensions and metabolic activity using small animal PET imaging. Methods: Tumor xenografts were induced into ADKO mice by s.c injection of GIST882 cells into the right leg. After 30 days, tumors grew in all animals (volume 0,2-0,3 cm3). Animals were randomised into 7 groups of 6 animals each for different treatment regimens: * No therapy (control) * I (150 mg/kg b.i.d.) oral gavage for 6 days, then once/day because of toxicity * E (10 mg/kg/d.) oral gav...