Positron emission tomography probes targeting bromodomain and extra-terminal (BET) domains to enable in vivo neuroepigenetic imaging

Ping Bai; Hsiao-Ying Wey; Debasis Patnaik; Xiaoxia Lu; Yu Lan; Johanna Rokka; Fiedler Stephanie; Stephen J Haggarty; Changning Wang

doi:10.1039/c9cc06734e

Positron emission tomography probes targeting bromodomain and extra-terminal (BET) domains to enable in vivo neuroepigenetic imaging

Chem Commun (Camb). 2019 Oct 24;55(86):12932-12935. doi: 10.1039/c9cc06734e.

Authors

Ping Bai¹, Hsiao-Ying Wey², Debasis Patnaik³, Xiaoxia Lu⁴, Yu Lan², Johanna Rokka², Fiedler Stephanie², Stephen J Haggarty³, Changning Wang²

Affiliations

¹ Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, P. R. China. pbai@mgh.harvard.edu and Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. cwang15@mgh.harvard.edu and University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
² Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. cwang15@mgh.harvard.edu.
³ Chemical Neurobiology Laboratory, Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁴ Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, P. R. China. pbai@mgh.harvard.edu.

PMID: 31599282
DOI: 10.1039/c9cc06734e

Abstract

Here, we report the development of novel PET radiotracer ([11C]CW22) of BET proteins. In vivo imaging results in rodents and nonhuman primates (NHP) demonstrate that [11C]CW22 has excellent brain uptake, good specificity, good selectivity, suitable metabolism, appropriate kinetics and distribution in the brain. Our studies demonstrated that [11C]CW22 exhibits ideal properties as a PET imaging probe of BET proteins for further validation.

MeSH terms

Animals
Blood-Testis Barrier / metabolism
Brain / diagnostic imaging*
Brain / metabolism
Carbon Radioisotopes / chemistry
Crystallography, X-Ray
Kinetics
Macaca
Mice
Molecular Conformation
Nerve Tissue Proteins / chemistry
Neurons
Positron-Emission Tomography*
Protein Domains
Radiopharmaceuticals / chemistry*
Radiopharmaceuticals / metabolism
Receptors, Cell Surface / chemistry

Substances

Carbon Radioisotopes
Carbon-11
Dner protein, mouse
Nerve Tissue Proteins
Radiopharmaceuticals
Receptors, Cell Surface