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The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the  in vivo  and  in vitro  treatment effect of everolimus in neuroendocrine tumors and evaluated the performance of  18 F-FDG and the proliferation tracer  18 F-FLT for treatment response assessment by PET imaging.    Methods  The effect of everolimus on the human carcinoid cell line H727 was examined  in vitro  with the MTT assay and  in vivo  on H727 xenograft tumors. The mice were scanned at baseline with  18 F-FDG or  18 F-FLT and then treated with either placebo or everolimus (5 mg/kg daily) for 10 days. PET/CT scans were repeated at day 1,3 and 10.    Results  Everolimus showed significant inhibition of H727 cell proliferation  in vitro  at concentrations above 1 nM.  In vivo  tumor volumes measured relative to baseline were significantly lower in the everolimus group compared to the control group at day 3 (126±6% vs. 152±6%; p = 0.016), day 7 (164±7% vs. 226±13%; p<0.001) and at day 10 (194±10% vs. 281±18%; p<0.001). Uptake of  18 F-FDG and  18 F-FLT showed little differences between control and treatment groups, but individual mean uptake of  18 F-FDG at day 3 correlated with tumor growth day 10 (r 2  = 0.45; P = 0.034),  18 F-FLT mean uptake at day 1 correlated with tumor growth day 7 (r 2  = 0.63; P = 0.019) and at day 3  18 F-FLT correlated with tumor growth day 7 (r 2  = 0.87; P<0.001) and day 10 (r 2  = 0.58; P = 0.027).    Conclusion  Everolimus was effective  in vitro  and  in vivo  in human xenografts lung carcinoid NETs and especially early  18 F-FLT uptake predicted subsequent tumor growth. We suggest that  18 F-FLT PET can be used for tailoring therapy for neuroendocrine tumor patients through early identification of responders and non-responders.

18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors: Studies in Human Tumor Xenografts in Mice