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 gavage * E (10 mg/kg/d.) + I (150 mg/kg b.i.d.) * N (75 mg/kg/d.) oral gavage * N (75 mg/kg/d.) + I (150 mg/kg b.i.d) * I (300 Mg/kg q.d.) i.p. injection. Small animal PET (GE Explore tomography) was performed in one animal per group at base-line, after 7 and 13 days of treatment. The base-line FDG uptake was positive in all evaluated animals. Results: After 3 days of treatment all animals of the I i.p. treatment group died. In other groups, treatments were administered for 13 days and only 3 animals out of 36 died during the study (two in the I group, one in E + I group). Tumor volume (cm3) after 13 days of treatment: * Control: 1,2 * E, E + I, N + I: < 0,5 * N alone and I alone: 0,5-0,8. Micro-PET (FDG / SUV / TBR): * E: FDG was strongly reduced by E both as a single agent and in combination with I respectively: 3,1 > 2,3 > 1,9 and 2,5 > 2,3 > 0 * N also reduced FDG: 2,2 > 1,4 > 1,7 * N + I: 2,7> 3,2> 2,8 * I: 2,9 > 2, however, the mouse subjected to the first 2 PET scans died before the third scan. Conclusions: We report the in vivo evaluation of combined treatments vs single agent in GIST. All drugs showed activity as single agents. The combination E plus I appeared to be more active regimen in comparison to the others, both in terms of inhibiting tumor growth and FDG Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis