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. Our study evaluated the potential radiosensitizing effects of inhibition of nicotineamide phosphoribosyltransferase on ¹⁷⁷Lu-DOTATATE treatment in a NET model. Nude mice xenografted with the human NET cell line GOT1 were treated with semiefficient doses of ¹⁷⁷Lu-DOTATATE (7.5 MBq, intravenously) or the nicotineamide phosphoribosyltransferase inhibitor GMX1778 (100 mg/kg/wk, orally). Median time to tumor progression (tumor volume larger than at day 0) was 3 d for controls, 7 d for single-dose GMX1778, 28 d for single-dose ¹⁷⁷Lu-DOTATATE, 35 d for 3 weekly doses of GMX1778, and 98 d for combined treatment with ¹⁷⁷Lu-DOTATATE and GMX1778 × 1. After ¹⁷⁷Lu-DOTATATE and 3 weekly doses of GMX1778, none of the tumors progressed within 120 d. GMX1778 enhances the efficacy of ¹⁷⁷Lu-DOTATATE treatment and induces a prolonged antitumor response.