The Effects Of MTOR Inhibitors Everolimus On Neuroendocrine Tumors

Objectives:To evaluate the effect of everolimus, an inhibitor of (mammalian target of rapamycin) mTOR, on neuroendocrine tumors and the performance of18F-FDG for treatment response assessment by microPET imaging; to provide evidences for the application of everolimus in the treatment for neuroendocrine tumors.Methods:BALB/c nude mice bearing subcutaneous human BON1neuroendocrine tumor xenografts were treated with either the mTOR inhibitor everolimus (1.5mg/kg/d) or vehicle, until the end of the experiment. Tumor size was measured by caliper and animals were weighted third times a week; F-FDG uptake was evaluated by microPET on week0,1,2and3. At day28, the animals were sacrificed and the tumors were excised for histopathology. Levels of Ki-67, caspase-3and vWF were assessed by immunohistochemistry.Results:In vivo tumor volumes measured relative to baseline were significantly lower in the everolimus group compared to the control group from day7to day28(P<0.05). During the treatment period, no significant difference in tumor18F-FDG uptake was observed between the treatment and control group at any time. At week3,18F-FDG uptake was significantly increased in the control group when compared to baseline, whereas no difference in F-FDG uptake was observed in the treatment group on week3when compared to baseline. In ex vivo studies, everolimus treatment induced a significant decrease in the ratio of Ki-67positive cells and MVD compared with the control group. But no difference in the IOD value of caspase-3was observed between the two groups.Conclusions:Our results suggested that everolimus was effective in vivo in a human xenografts neuroendocrine tumor and18F-FDG PET may not be a suitable method for treatment response assessment of everolimus for neuroendocrine tumor patients.