Development of a new ¹⁸F-labeled PET tracer for potential application to HDAC2 neuroimaging

Histone deacetylases (HDACs) play an important role in the regulation of cellular functions and have attracted highly attention as promising therapeutic targets for the treatment of neurodegenerative diseases. Among the various HDAC isoforms, HDAC2 have shown significantly to be involved in the emergence and progression of neurodegenerative disorders. However, research on the biological mechanism of HDAC2 requires more advanced tools. In this study, we present the radiosynthesis of [¹⁸F]HYF005 with high radiochemical purity and satisfactory molar activity. In vitro autoradiographic studies shown [¹⁸F]HYF005 has good binding specificity in mice brain tissues. In vivo evaluation of PET imaging in rodent models confirmed that [¹⁸F]HYF005 exhibits good BBB penetration, with a highest brain peak uptake SUV = 1.2 in mice. Our study indicates that [¹⁸F]HYF005 can be used as a potential PET probe for imaging the HDAC2 system in the brain and provides a foundation for the future development of more potential HDAC2 targeting PET probes.