Year: 2023
Type: article
Abstract: Background Novel PET tracers were designed and tested to target the NLRP3 inflammasome in the brain to develop biomarkers for neuroinflammation in AD. Method A novel chemical scaffold was rationally designed based on our previously developed NLRP3 inhibitors. One of the compounds, YM8, was radiolabeled with C‐11, and radiotracer was characterized in mouse models and non‐human primates (NHPs). Result The studies in wild type and nlrp3‐/‐ mouse brain tissues demonstrated that [11C]YM8 is a NLRP3 specific PET tracer with Bmax/Kd > 10, hinting to be a suitable CNS PET tracer. Studies in mice revealed rapid and high brain uptake of [11C]YM8. PET/MR studies of [11C]YM8 in NHPs demonstrated excellent brain uptake and radiometabolism stability as well as fast washout from blood. Conclusion A novel C‐11 labeled NRP3 PET radiotracer was developed and demonstrated to serve as a suitable CNS PET tracer to monitor inflammatory responses in the brain.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.071080
Authors: Yiming Xu, Yulong Xu, Savannah Biby, Changning Wang, Shijun Zhang, Medicinal Chemistry, VCU
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390194114