A Self‐immobilizing <scp>PET</scp> Tracer for Imaging of <scp>H₂O₂</scp> Level in the Brain

Comprehensive Summary Reactive oxygen species (ROS) are involved in the onset and development of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Hydrogen peroxide (H 2 O 2 ), a key type of ROS, is overexpressed in the early stages of AD and PD and is involved in the disease progression. Assessing H 2 O 2 levels in the brain is considered to be a valuable tool for detecting neurodegenerative diseases and exploring their pathogenesis. In this study, we developed two self‐immobilizing PET tracers ( [ 18 F]HYAS and [ 18 F]HYAT ) based on a quinone methide (QM) scaffold for non‐invasive imaging of H 2 O 2 in the brain. Both tracers can respond to H 2 O 2 by forming a QM intermediate, which rapidly reacts with nucleophiles. [ 18 F]HYAT , with proper physicochemical properties, is able of crossing the blood‐brain barrier. Increased uptake of [ 18 F]HYAT was observed in the brains of mice treated with 1‐methyl‐4‐phenyl‐ l,2,3,6‐tetrahydropyridine (MPTP), indicating that [ 18 F]HYAT is a useful tracer for PET imaging of H 2 O 2 in the brain.