Neuroscience conference 2022

Changning Wang

Harvard Medical School, USA

Title: PET imaging probes for neuroinflammation

Abstract

The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is an essential component of innate immunity that senses both exogenous microbial products and endogenous dangers associated with cellular stress and damage. RIPK1 is a death-domain containing serine/threonine kinase, which was involved in regulating cell death. RIPK1 is dysregulated by microglial cells in human brains and mediates a disease-associated microglial response, which is related to an inflammatory response. Despite the preclinical success and early clinical trial of these inhibitors, a large knowledge gap exists between animal models and human diseases. In our opinion, this knowledge gap can in large part be filled by translational neuroimaging with the availability of a PET imaging biomarker. In past years, we have designed, radiosynthesized and evaluated several RIPK1 and NLRP3 inhibitors as potential PET imaging probes, and some candidates displayed good brain uptake, good specificity and selectivity that supporting the application as PET tracers in humans. 
In summary, we fully expect that our new PET probes for neuroinflammation will be useful for human neuroimaging study and are also able to serve as a putative imaging biomarker that can significantly improve understanding of the pathogenesis of human diseases and rapidly enhance the drug development. 

Biography

Changning Wang, PhD, has a unique and broad background in molecular imaging, medicinal chemistry, pharmaceutical sciences and neuroscience. After finishing his doctoral studies, he joined Martinos Center for Biomedical Imaging as a research fellow and later as a trainee in the Harvard/MGH Nuclear Medicine Training Program, to expand his research skills in clinical imaging research. He is now an assistant professor at Harvard Medical School. In the past few years, he has developed [11C]Martinostat as a robustly brain penetrant imaging agent with selectivity for class I HDACs. [11C]Martinostat is the first and only-to-date PET imaging probe for epigenetic research. He designed this probe in only a half year, an extremely short time. The exploratory IND for [11C]Martinostat was approved by the FDA for first-in-human trials and is the first tool of its kind available to characterize HDAC expression in the living human brain. Dr. Wang is leading the project of [11C]Martinostat clinical imaging in several patient groups. He is also working on developing new PET imaging probes targeting other epigenetic enzymes and using these tools for new drug discovery.