Peptide receptor radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3]octreotate in combination with RAD001 treatment: further investigations on tumor metastasis and response in the rat pancreatic CA20948 tumor model

Background Previously, we reported on the unexpected development of distant metastases in the subcutaneous rat pancreas CA20948 tumor model after 4.5 weeks of treatment with RAD001-only or in combination with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) (Cancer Res. 73:12-8, 2013). Moreover, the combination therapy was less effective compared to 177Lu-DOTATATE-only. In the current study, we address the following questions: (1) Why was the combination therapy less effective? Is 177Lu-DOTATATE tumor uptake affected by pretreatment with RAD001? (2) Could sudden cessation of RAD001 therapy cause the development of distant metastases? (3) Is 177Lu-DOTATATE an effective treatment option for these metastases?