NAMPT inhibitor GMX1778 enhances the efficacy of 177Lu-DOTATATE treatment of neuroendocrine tumors.

Neuroendocrine tumors (NETs) can be treated by peptide receptor radionuclide therapy using radiolabeled somatostatin analogs. However, the efficacy of such treatment is low and needs to be optimized.,To evaluate the potential radiosensitizing effects of NAMPT inhibition on Lu-DOTATATE treatment in a NET model.,Nude mice xenografted with the human NET cell line GOT1 were treated with semi-efficient doses of Lu-DOTATATE (7,5 MBq, i.v.) and/or GMX1778 (100 mg/kg/week, p.o.).,Median time to tumor progression (tumor volume larger than at day 0) was 3 days for controls, 7 days for single dose GMX1778, 28 days for single dose Lu-DOTATATE and 35 days for 3 weekly doses of GMX1778. Combined treatment with Lu-DOTATATE and GMX1778 x1 resulted in a median time to progression of 98 days. After Lu-DOTATATE and 3 weekly doses of GMX1778 none of the tumors progressed within 120 days.,The NAMPT inhibitor GMX1778 enhances the efficacy of Lu-DOTATATE treatment and induces a prolonged antitumor response. Combinations of radiolabeled somatostatin analogs and radiosensitizing drugs should be further evaluated to optimize the efficacy of peptide receptor radionuclide therapy in NETs.