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Epigenetic Treatment with Histone Deacetylase Inhibitor Enhances Uptake of [111In]In-DOTA-TATE by Increased SST2 Expression on Neuroendocrine Tumor Cells


Introduction: The somatostatin-2 receptor (SST2) is a target for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NETs). By using epigenetic drugs, which can regulate gene transcription, PRRT efficacy may be further improved due to enhanced SST2 expression.

Aim(s): To increase SST2 expression on NET cells by treating the cells with different histone deacetylase inhibitors (HDACis).

Materials and methods: Human pancreatic NET BON-1 cells were used. Cell growth assays were performed to determine the EC50 of 6 different HDACis after a 7 day treatment, i.e. VPA, CI-994, ENT, LMK-235, MOC and PAN. Subsequently, cells were incubated with the calculated EC50 of the HDACis for 7 days. SST2 mRNA expression levels were determined by RT-qPCR and uptake studies were performed by incubating cells with 1mL of 1nM [111In]In-DOTA-TATE (50MBq/nmol), +/- 1µM unlabeled DOTA-TATE. Moreover, RT-qPCR was used to determine reversibility 1, 3 and 7 days after HDACi withdrawal.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Klomp I

Authors: Klomp I, Dalm S, van Koetsveld P, Dogan-Oruç F, de Jong M,

Keywords: neuroendocrine tumors, bon-1, epigenetic, histone, histone deacetylase inhibitor, HDACi, upregulation, reversibility, somatostatin receptor-2, somatostatin,

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