目的是确定组蛋白脱乙酰酶 (HDAC) 抑制剂 (HDACis) 对生长抑素 2 型受体 (SSTR2) 表达和体外和体内 [111In]In-/[177Lu]Lu-DOTA-TATE 摄取的影响。用 HDACis（即恩替司他、莫西司他 (MOC)、LMK-235、CI-994 或帕比司他 (PAN)）治疗人细胞系 NCI-H69（小细胞肺癌）和 BON-1（胰腺神经内分泌肿瘤），并且测量了SSTR2 mRNA表达水平和[111In]In-DOTA-TATE摄取。此外，用载体和 HDACi 治疗的 NCI-H69 和 BON-1 荷瘤小鼠注射放射性标记的 DOTA-TATE，然后进行生物分布研究。此外，还测定了异种移植物以及 NCI-H69、BON-1、NCI-H727（人肺类癌）和 GOT1（人中肠神经内分泌肿瘤）细胞的 SSTR2 和 HDAC mRNA 表达。HDACi 治疗在体外产生了预期的效果。然而，在 HDACi 治疗 NCI-H69 荷瘤动物后，未观察到肿瘤 DOTA-TATE 摄取显着增加，而在 MOC、CI-994 和 PAN 治疗后，肿瘤 SSTR2 mRNA 和/或蛋白表达水平显着上调，即最大分别为 2.1 倍和 1.3 倍。对 PAN 处理的 BON-1 异种移植物的分析仅表明 SSTR2 mRNA 表达水平增加。 BON-1 和 NCI-H69 异种移植物中 HDAC 和 SSTR2 表达的比较显示，BON-1 异种移植物中 6/11 HDAC 的表达显着较高。在这些 HDAC 中，在所研究的细胞系中发现 HDAC3 和 SSTR2 表达之间存在显着的负相关（Pearson r=-0.92）。 总之，体内 HDACi 治疗后，肿瘤对放射性标记的 DOTA-TATE 的摄取水平并未增强，但是，根据所使用的抑制剂，观察到 SSTR2 表达水平增加。版权所有 © 2023。由 Elsevier Inc. 出版。

The aim was to determine the effect of histone deacetylase (HDAC) inhibitors (HDACis) on somatostatin type-2 receptor (SSTR2) expression and [111In]In-/[177Lu]Lu-DOTA-TATE uptake in vitro and in vivo.The human cell lines NCI-H69 (small-cell lung carcinoma) and BON-1 (pancreatic neuroendocrine tumor) were treated with HDACis (i.e. entinostat, mocetinostat (MOC), LMK-235, CI-994 or panobinostat (PAN)), and SSTR2 mRNA expression levels and [111In]In-DOTA-TATE uptake were measured. Furthermore, vehicle- and HDACi-treated NCI-H69 and BON-1 tumor-bearing mice were injected with radiolabeled DOTA-TATE followed by biodistribution studies. Additionally, SSTR2 and HDAC mRNA expression of xenografts, and of NCI-H69, BON-1, NCI-H727 (human pulmonary carcinoid) and GOT1 (human midgut neuroendocrine tumor) cells were determined.HDACi treatment resulted in the desired effects in vitro. However, no significant increase in tumoral DOTA-TATE uptake was observed after HDACi treatment in NCI-H69 tumor-bearing animals, whereas tumoral SSTR2 mRNA and/or protein expression levels were significantly upregulated after treatment with MOC, CI-994 and PAN, i.e. a maximum of 2.1- and 1.3-fold, respectively. Analysis of PAN-treated BON-1 xenografts solely demonstrated increased SSTR2 mRNA expression levels. Comparison of HDACs and SSTR2 expression in BON-1 and NCI-H69 xenografts showed a significantly higher expression of 6/11 HDACs in BON-1 xenografts. Of these HDACs, a significant inverse correlation was found between HDAC3 and SSTR2 expression (Pearson r = -0.92) in the studied cell lines.To conclude, tumoral uptake levels of radiolabeled DOTA-TATE were not enhanced after HDACi treatment in vivo, but, depending on the applied inhibitor, increased SSTR2 expression levels were observed.Copyright © 2023. Published by Elsevier Inc.