1. Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment.
- Author
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Guenter R, Aweda T, Carmona Matos DM, Jang S, Whitt J, Cheng YQ, Liu XM, Chen H, Lapi SE, and Jaskula-Sztul R
- Subjects
- Animals, Cell Line, Tumor, Cell Separation, Depsipeptides administration & dosage, Flow Cytometry, Gene Expression Regulation, Neoplastic drug effects, Humans, Male, Mice, Neuroendocrine Tumors pathology, Organometallic Compounds administration & dosage, Pancreas diagnostic imaging, Pancreas pathology, Pancreatic Neoplasms pathology, Tissue Array Analysis, Transcription, Genetic drug effects, Xenograft Model Antitumor Assays, Histone Deacetylase Inhibitors administration & dosage, Molecular Imaging methods, Neuroendocrine Tumors diagnostic imaging, Pancreatic Neoplasms diagnostic imaging, Positron Emission Tomography Computed Tomography methods, Receptors, Somatostatin metabolism
- 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2020
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