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

Journal article
Authors Anna-Karin Elf
Peter Bernhardt
Tobias Hofving
Yvonne Arvidsson
Eva Forssell-Aronsson
Bo Wängberg
Ola Nilsson
Viktor Johanson
Published in Journal of Nuclear Medicine
Volume 58
Issue 2
Pages 288-292
ISSN 0161-5505
Publication year 2017
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine, Department of Pathology
Sahlgrenska Cancer Center
Pages 288-292
Language en
Subject categories Cancer and Oncology


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 (177)Lu-DOTATATE treatment in a NET model.Nude mice xenografted with the human NET cell line GOT1 were treated with semi-efficient doses of (177)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 (177)Lu-DOTATATE and 35 days for 3 weekly doses of GMX1778. Combined treatment with (177)Lu-DOTATATE and GMX1778 x1 resulted in a median time to progression of 98 days. After (177)Lu-DOTATATE and 3 weekly doses of GMX1778 none of the tumors progressed within 120 days.The NAMPT inhibitor GMX1778 enhances the efficacy of (177)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.

Page Manager: Webmaster|Last update: 9/11/2012

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