Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells
The peptide receptor radionuclide therapy (PRRT) with <sup>177</sup>Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET...
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doaj-354eb6939a664b73b62204f49c37919f2021-01-11T00:01:44ZengMDPI AGCancers2072-66942021-01-011323223210.3390/cancers13020232Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor CellsRashmi G. Shah0Marine A. Merlin1Samuel Adant2Fayçal Zine-Eddine3Jean-Mathieu Beauregard4Girish M. Shah5Neuroscience Division, CHU de Québec Université Laval Research Center, Québec City, QC G1V 4G2, CanadaNeuroscience Division, CHU de Québec Université Laval Research Center, Québec City, QC G1V 4G2, CanadaNeuroscience Division, CHU de Québec Université Laval Research Center, Québec City, QC G1V 4G2, CanadaNeuroscience Division, CHU de Québec Université Laval Research Center, Québec City, QC G1V 4G2, CanadaOncology Division, CHU de Québec Université Laval Research Center, Québec City, QC G1R 2J6, CanadaNeuroscience Division, CHU de Québec Université Laval Research Center, Québec City, QC G1V 4G2, CanadaThe peptide receptor radionuclide therapy (PRRT) with <sup>177</sup>Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.https://www.mdpi.com/2072-6694/13/2/232NETs: neuroendocrine tumorsSSTR: somatostatin receptorsPRRT: peptide receptor radionuclide therapyLuTate: <sup>177</sup>Lu-DOTA-octreotatechemotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rashmi G. Shah Marine A. Merlin Samuel Adant Fayçal Zine-Eddine Jean-Mathieu Beauregard Girish M. Shah |
spellingShingle |
Rashmi G. Shah Marine A. Merlin Samuel Adant Fayçal Zine-Eddine Jean-Mathieu Beauregard Girish M. Shah Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells Cancers NETs: neuroendocrine tumors SSTR: somatostatin receptors PRRT: peptide receptor radionuclide therapy LuTate: <sup>177</sup>Lu-DOTA-octreotate chemotherapy |
author_facet |
Rashmi G. Shah Marine A. Merlin Samuel Adant Fayçal Zine-Eddine Jean-Mathieu Beauregard Girish M. Shah |
author_sort |
Rashmi G. Shah |
title |
Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells |
title_short |
Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells |
title_full |
Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells |
title_fullStr |
Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells |
title_full_unstemmed |
Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of <sup>177</sup>Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells |
title_sort |
chemotherapy-induced upregulation of somatostatin receptor-2 increases the uptake and efficacy of <sup>177</sup>lu-dota-octreotate in neuroendocrine tumor cells |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-01-01 |
description |
The peptide receptor radionuclide therapy (PRRT) with <sup>177</sup>Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery. |
topic |
NETs: neuroendocrine tumors SSTR: somatostatin receptors PRRT: peptide receptor radionuclide therapy LuTate: <sup>177</sup>Lu-DOTA-octreotate chemotherapy |
url |
https://www.mdpi.com/2072-6694/13/2/232 |
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