Development of a Novel Positron Emission Tomography (PET) Radiotracer Targeting Bromodomain and Extra-Terminal Domain (BET) Family Proteins

Frontiers in Molecular Biosciences

Zude Chen¹  Hao Wang¹  Yu Lan¹  Stephanie Fiedler¹  Robin Striar¹  Changning Wang¹  Xiaoxia Lu²  Ping Bai³ 

[1] Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States;Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China;University of Chinese Academy of Sciences, Beijing, China;

关键词: epigenetic;    bromodomain;    PET;    radiotracer;    imaging;   

DOI  :  10.3389/fmolb.2020.00198

来源: DOAJ

【 摘 要 】

Bromodomain and extra-terminal domain (BET) family proteins have become a hot research area because of their close relationship with a variety of human diseases. The non-invasive imaging technique, such as positron emission tomography (PET), provides a powerful tool to visualize and quantify the BET family proteins that accelerating the investigation of this domain. Herein, we describe the development of a promising PET probe, [11C]1, specifically targeting BET family proteins based on the potent BET inhibitor CF53. [11C]1 was successfully radio-synthesized with good yield and high purity after the optimization of radiolabeling conditions. The in vivo bio-activities evaluation of [11C]1 was performed using PET imaging in rodents. The results demonstrated that [11C]1 has favorable uptake in peripheral organs and moderate uptake in the brain. Further blocking studies indicated the high binding specificity and selectivity for BET proteins of this probe. Our findings suggest that [11C]1 is a promising BET PET probe for BET proteins as well as epigenetic imaging.

【 授权许可】

Unknown