Development of New Positron Emission Tomography Radiotracer for BET Imaging.
The bromodomain and extraterminal domain (BET) inhibitors have been extensively studied for tumor treatment in the past few years. Recently, BET-containing proteins have been reported to play a key role in brain functions, such as learning and memory. BET proteins have also been shown to be a potential therapeutic target for substance abuse disorders. Development of a molecular probe for noninvasive imaging will elucidate the distribution and functional roles of BET in the living subject and accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and pilot imaging of a novel BET imaging agent, [11C]MS417. Our imaging results demonstrate that this probe has moderate brain uptake, good specificity, good selectivity, and appropriate kinetics and distribution. [11C]MS417 is an ideal lead compound for further optimization of clinical BET PET radiotracer tools and MS417 could be used as a blood-brain-barrier-penetrant compound for preclinical research.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.
Changning
C
Wang
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.
Frederick A
FA
Schroeder
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.
Jacob M
JM
Hooker
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D018797:Cell Cycle Proteins; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015898:Tomography Scanners, X-Ray Computed; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000092468:Bromodomain Containing Proteins
D001381:Azepines; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D019275:Radiopharmaceuticals; D014157:Transcription Factors; D014230:Triazoles; C561695:(+)-JQ1 compound; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins
Bromodomain; PET; [11C]MS417; radiotracer