NAMPT Inhibitor GMX1778 Enhances the Efficacy of 177Lu-DOTATATE Treatment of Neuroendocrine Tumors
| Autor: | Tobias Hofving, Yvonne Arvidsson, Anna-Karin Elf, Peter Bernhardt, Eva Forssell-Aronsson, Ola Nilsson, Viktor Johanson, Bo Wängberg |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Peptide receptor Mice Nude Pharmacology Neuroendocrine tumors Octreotide Guanidines Radiation Tolerance 03 medical and health sciences Mice 0302 clinical medicine 177Lu-DOTATATE Organometallic Compounds Medicine Animals Humans Radiology Nuclear Medicine and imaging Nicotinamide Phosphoribosyltransferase Mice Inbred BALB C Cyanides biology Dose-Response Relationship Drug business.industry Dose-Response Relationship Radiation Drug Synergism medicine.disease Neuroendocrine Tumors 030104 developmental biology Somatostatin Treatment Outcome Cell culture Tumor progression 030220 oncology & carcinogenesis Radionuclide therapy biology.protein Phosphoribosyltransferase Cytokines Drug Therapy Combination Female Radiopharmaceuticals business |
| Zdroj: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 58(2) |
| ISSN: | 1535-5667 |
| Popis: | 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. METHODS 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). 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-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. CONCLUSION GMX1778 enhances the efficacy of 177Lu-DOTATATE treatment and induces a prolonged antitumor response. |
| Databáze: | OpenAIRE |
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