Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment

Rachael Guenter, Tolulope Aweda, Danilea M. Carmona Matos, Samuel Jang, Jason Whitt, Yi Qiang Cheng, X. Margaret Liu, Herbert Chen, Suzanne E. Lapi, Renata Jaskula-Sztul

Research output: Contribution to journalArticle

Abstract

Background: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2. Methods: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography. Results: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration. Conclusion: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalSurgery (United States)
Volume167
Issue number1
DOIs
StatePublished - Jan 2020

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Neuroendocrine Tumors
Histone Deacetylase Inhibitors
Neuroendocrine Cells
Therapeutics
Tumor Cell Line
somatostatin receptor 2
Somatostatin
Heterografts
Pancreas
Flow Cytometry
Proteins
Up-Regulation
Messenger RNA
Positron Emission Tomography Computed Tomography

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Guenter, Rachael ; Aweda, Tolulope ; Carmona Matos, Danilea M. ; Jang, Samuel ; Whitt, Jason ; Cheng, Yi Qiang ; Liu, X. Margaret ; Chen, Herbert ; Lapi, Suzanne E. ; Jaskula-Sztul, Renata. / Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment. In: Surgery (United States). 2020 ; Vol. 167, No. 1. pp. 189-196.
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title = "Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment",
abstract = "Background: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2. Methods: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography. Results: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration. Conclusion: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.",
author = "Rachael Guenter and Tolulope Aweda and {Carmona Matos}, {Danilea M.} and Samuel Jang and Jason Whitt and Cheng, {Yi Qiang} and Liu, {X. Margaret} and Herbert Chen and Lapi, {Suzanne E.} and Renata Jaskula-Sztul",
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Guenter, R, Aweda, T, Carmona Matos, DM, Jang, S, Whitt, J, Cheng, YQ, Liu, XM, Chen, H, Lapi, SE & Jaskula-Sztul, R 2020, 'Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment', Surgery (United States), vol. 167, no. 1, pp. 189-196. https://doi.org/10.1016/j.surg.2019.05.092

Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment. / Guenter, Rachael; Aweda, Tolulope; Carmona Matos, Danilea M.; Jang, Samuel; Whitt, Jason; Cheng, Yi Qiang; Liu, X. Margaret; Chen, Herbert; Lapi, Suzanne E.; Jaskula-Sztul, Renata.

In: Surgery (United States), Vol. 167, No. 1, 01.2020, p. 189-196.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment

AU - Guenter, Rachael

AU - Aweda, Tolulope

AU - Carmona Matos, Danilea M.

AU - Jang, Samuel

AU - Whitt, Jason

AU - Cheng, Yi Qiang

AU - Liu, X. Margaret

AU - Chen, Herbert

AU - Lapi, Suzanne E.

AU - Jaskula-Sztul, Renata

PY - 2020/1

Y1 - 2020/1

N2 - Background: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2. Methods: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography. Results: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration. Conclusion: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.

AB - Background: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2. Methods: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography. Results: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration. Conclusion: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.

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