Synthesis and Characterization of a Positron Emission Tomography Imaging Probe Selectively Targeting the Second Bromodomain of Bromodomain Protein BRD4.

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.