Synergistic effect of combined treatment with 177Lu-DOTATATE and Everolimus in neuroendocrine tumors as monitored by 18F-FDG-PET: Studies in human neuroendocrine xenografts

57 Objectives Patients with Neuroendocrine tumors are treated with 177Lu-DOTATATE radionuclide therapy with varying effects. Recently Everolimus (RAD001), an oral mTOR inhibitor, has shown promising results in the treatment of neuroendocrine tumors. We hypothesized that a combination of these treatments would be beneficial. Methods Mice with H727-xenografts were treated with either daily i.p injections of Everolimus (5 μg/g), weekly (2 in total) i.v injections of 177Lu-DOTATATE (20 MBq) or a combination of both treatments. Tumors (n=10 in each group) were defined on PET/CT images at baseline, day 1, 4, 8 and 13. FDG uptake was calculated as mean standardized uptake value (SUV). Results Relative tumor-growth at day 13 (mean ± SEM): Vehicle (764 ± 83%), 177Lu-DOTATATE (625 ± 89%), Everolimus (365 ± 33%) and the combination-therapy (243 ± 44%). The combination therapy was significantly better than Everolimus alone (best single treatment), p=0.04. FDG-SUVs at day 1 were significantly lower for the combination group compared to Vehicle, p = 0.0003. Conclusions Mice treated with a combination of 177Lu-DOTATATE and Everolimus had greater anti-tumor effect than with the agents administered separately