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

Abstract

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 [ 11 C]1 as a BRD4 BD2 bromodomain PET imaging radioligand. Our preliminary PET imaging results in rodents demonstrated that [ 11 C]1 had suitable biodistribution in peripheral organs and tissues. Further blocking studies indicated that [ 11 C]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.

Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice

“…The PET/CT imaging studies in rodents in this work were referred to our previous work. , Micro-PET/CT imaging was performed in two groups: male C57BL/6 mice (6 months old), used for general brain imaging and blocking studies. After intravenous injection of [ 11 C]­PB94 (3.7–5.6 Mbq per animal), a 60 min dynamic PET acquisition was performed followed by a 10 min CT scan.…”

Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

“…The PET/CT imaging studies in rodents in this work were referred to our previous work 46 , 47 . Micro-PET/CT imaging was performed in two groups: male C57BL/6 mice, used for general brain imaging and blocking studies; female 5xFAD transgenic mice and their age and gender-matched WT mice, used as AD model.…”

Visualization of Receptor-Interacting Protein Kinase 1 (RIPK1) by Brain Imaging with Positron Emission Tomography

“…PET/CT image analysis was performed according to our previously reported method. , Briefly, volumes of interests (VOIs) were generated manually in the forms of spheres under the guide of high-resolution CT structural images and summed PET data in mice brain regions using the mouse (Ma-Benveniste-Mirrione) VOI atlas , with a radius no less than 1 mm to minimize partial volume effects. TACs were exported as the decay-corrected activity per unit volume.…”