Comparing the effect of multiple histone deacetylase inhibitors on sstr2 expression and [111in]in‐dotatate uptake in net cells

Maria J. Klomp, Simone U. Dalm, Peter M. van Koetsveld, Fadime Dogan, Marion de Jong, Leo J. Hofland*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
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The aim of this study was to increase somatostatin type‐2 receptor (SSTR2) expression on neuroendocrine tumor (NET) cells using histone deacetylase inhibitors (HDACis), potentially increasing the uptake of SSTR2‐targeted radiopharmaceuticals and subsequently improving treatment efficacy of peptide receptor radionuclide therapy (PRRT). Human NET cell lines BON‐1, NCI‐ H727, and GOT1 were treated with HDACis (i.e., CI‐994, entinostat, LMK‐235, mocetinostat, panobinostat, or valproic acid (VPA); entinostat and VPA were the HDACis tested in GOT1 cells) to examine SSTR2 mRNA expression levels and uptake of SSTR2‐targeting radiotracer [111In]In‐DO‐ TATATE. Reversibility of the induced effects was examined after drug‐withdrawal. Finally, the effect of VPA on radiosensitivity was investigated. A strong stimulatory effect in BON‐1, NCI‐H727, and GOT1 cells was observed after HDACi treatment, both on SSTR2 mRNA expression levels and [111In]In‐DOTATATE uptake. The effects of the HDACis were largely reversible over a period of seven days, demonstrating largest reductions within the first day. The reversibility profile of the induced effects suggests that proper timing of HDACi treatment is most likely essential for a beneficial outcome. In addition to increasing SSTR2 expression levels, VPA enhanced the radiosensitivity of all cell lines. In conclusion, HDACi treatment increased SSTR2 expression, and radiosensitivity was also enhanced upon VPA treatment.

Original languageEnglish
Article number4905
Issue number19
Early online date29 Sept 2021
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
Funding: This project is funded by an Erasmus MC grant (2017).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


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