Two tandem bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) family proteins have shown distinct roles in mediating gene transcription and expression. Inhibitors that interact with a specific bromodomain may contribute to a specific therapeutic potential with fewer side effects. However, little is known about this disease-related target. Positron emission tomography (PET) imaging could allow us to achieve in-depth knowledge of the BD2 bromodomain. Herein we describe the radiosynthesis and evaluation of [¹¹C]1 as a BRD4 BD2 bromodomain PET imaging radioligand. Our preliminary PET imaging results in rodents demonstrated that [¹¹C]1 had suitable biodistribution in peripheral organs and tissues. Further blocking studies indicated that [¹¹C]1 had good binding specificity toward the BD2 bromodomain. This study may pave the way for the development of a PET radioligand specifically targeting BD1/2 bromodomains as well as for the biological mechanism investigation of BD1/2 bromodomains.

中文翻译：

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选择性靶向溴结构域蛋白 BRD4 的第二溴结构域的正电子发射断层扫描成像探针的合成和表征

溴结构域和末端外结构域 (BET) 家族蛋白的两个串联溴结构域（BD1 和 BD2）在介导基因转录和表达中显示出不同的作用。与特定溴结构域相互作用的抑制剂可能有助于实现特定的治疗潜力，同时副作用更少。然而，对这种与疾病相关的目标知之甚少。正电子发射断层扫描 (PET) 成像可以让我们深入了解 BD2 溴结构域。在此，我们描述了 [ ¹¹ C] 1作为 BRD4 BD2 溴结构域 PET 成像放射性配体的放射合成和评估。我们在啮齿动物中的初步 PET 成像结果表明 [ ¹¹ C] 1在外周器官和组织中具有合适的生物分布。进一步的阻断研究表明[ ¹¹ C] 1对BD2溴结构域具有良好的结合特异性。该研究可能为开发专门针对 BD1/2 溴结构域的 PET 放射性配体以及 BD1/2 溴结构域的生物学机制研究铺平道路。