Development of a novel HDAC6 PET imaging agent uncovers associations between HDAC6 overexpression and neuroinflammation in depression.

ABSTRACT: Histone deacetylase 6 (HDAC6) represents a compelling target in major depressive disorder (MDD) pathophysiology, yet in vivo investigation has been constrained by inadequate imaging capabilities. Here, we report the development and validation of [¹⁸F]PB200, a novel positron emission tomography (PET) radiotracer specifically targeting brain HDAC6. PB200 was engineered with nanomolar affinity, high HDAC6 selectivity, and excellent blood-brain barrier permeability. [¹⁸F]PB200 was successfully synthesized in a radiochemical yield of 13 ± 4 % and validated through in vitro autoradiography and in vivo PET imaging across rodent and non-human primate models. We subsequently employed [¹⁸F]PB200 alongside TSPO-targeted [¹⁸F]FEPPA PET imaging in a chronic u

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC12834932 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature