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Oncotarget. 2018 May 15;9(37):24693-24706. doi: 10.18632/oncotarget.25266. eCollection 2018 May 15.

Potentiation of 177Lu-octreotate peptide receptor radionuclide therapy of human neuroendocrine tumor cells by PARP inhibitor.

Purohit NK1,2,3, Shah RG1,2,3, Adant S1,2,3,4,5, Hoepfner M6, Shah GM1,2,3, Beauregard JM2,4,5.

Author information

1
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, Canada.
2
Cancer Research Center, Université Laval, Quebec City, Canada.
3
Neurosciences and Oncology Branches of CHU de Québec, Université Laval Research Center, Quebec City, Canada.
4
Department of Radiology and Nuclear Medicine, Université Laval, Quebec City, Canada.
5
Oncology Branch of CHU de Québec, Université Laval Research Center, Quebec City, Canada.
6
Institute of Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Abstract

For patients with inoperable neuroendocrine tumors (NETs) expressing somatostatin receptors, peptide receptor radionuclide therapy (PRRT) with 177Lu-[DOTA0-Tyr3]-octreotate (177Lu-octreotate) is one of the most promising targeted therapeutic options but it rarely achieves cure. Therefore, different approaches are being tested to increase the efficacy of 177Lu-octreotate PRRT in NET patients. Using the gastroenteropancreatic BON-1 and the bronchopulmonary NCI-H727 as NET cell models, here we report that pharmacological inhibitors of DNA repair-associated enzyme poly(ADP-ribose) polymerase-1 (PARPi) potentiate the cytotoxic effect of 177Lu-octreotate on 2D monolayer and 3D spheroid models of these two types of NET cells. PARPi mediates this effect by enhancing 177Lu-octreotate-induced cell cycle arrest and cell death. Thus, the use of PARPi may offer a novel option for improving the therapeutic efficacy of 177Lu-octreotate PRRT of NETs.

KEYWORDS:

177Lu-octreotate; PARP inhibitor; neuroendocrine tumors; peptide receptor radionuclide therapy; radiosensitization

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