The Development of the Novel Positron Emission Tomography Radiotracer for Selective HDAC8 Imaging

HDACs play important roles in various neurological disorders. Unlike other HDAC subtypes that have been extensively studied in neurodegenerative diseases, HDAC8 has only recently emerged as a regulator in the central nervous system. In this study, we designed and successfully radiosynthesized [¹¹C]HYF031 as a potential HDAC8 radioligand with acceptable radiochemical yield and purity. In vitro autoradiography and self-blocking dynamic PET/CT studies in C57BL/6 mice demonstrated specific binding of [¹¹C]HYF031 to HDAC proteins in the brain. Dynamic PET imaging further showed measurable brain uptake and pharmacokinetic properties compatible with PET imaging. Biodistribution studies indicated that the tracer is primarily metabolized through the hepatobiliary system. Overall, these results suggest that [¹¹C]HYF031 is a promising lead tracer for HDAC8 imaging.