1. NAMPT Inhibitor GMX1778 Enhances the Efficacy of 177Lu-DOTATATE Treatment of Neuroendocrine Tumors.
- Author
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Elf AK, Bernhardt P, Hofving T, Arvidsson Y, Forssell-Aronsson E, Wängberg B, Nilsson O, and Johanson V
- Subjects
- Animals, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Drug Synergism, Drug Therapy, Combination methods, Female, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Octreotide administration & dosage, Radiopharmaceuticals administration & dosage, Treatment Outcome, Cyanides administration & dosage, Cytokines antagonists & inhibitors, Guanidines administration & dosage, Neuroendocrine Tumors pathology, Neuroendocrine Tumors therapy, Nicotinamide Phosphoribosyltransferase antagonists & inhibitors, Octreotide analogs & derivatives, Organometallic Compounds administration & dosage, Radiation Tolerance drug effects
- Abstract
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
177 Lu-DOTATATE treatment in a NET model., Methods: Nude mice xenografted with the human NET cell line GOT1 were treated with semiefficient doses of177 Lu-DOTATATE (7.5 MBq, intravenously) or the nicotineamide phosphoribosyltransferase inhibitor GMX1778 (100 mg/kg/wk, orally)., Results: 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-dose177 Lu-DOTATATE, 35 d for 3 weekly doses of GMX1778, and 98 d for combined treatment with177 Lu-DOTATATE and GMX1778 × 1. After177 Lu-DOTATATE and 3 weekly doses of GMX1778, none of the tumors progressed within 120 d., Conclusion: GMX1778 enhances the efficacy of177 Lu-DOTATATE treatment and induces a prolonged antitumor response., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2017
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