A Self-immobilizing PET Tracer for Imaging of H₂O₂ Level in the Brain

Abstract

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 (H₂O₂), a key type of ROS, is overexpressed in the early stages of AD and PD and is involved in the disease progression. Assessing H₂O₂ 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 ([¹⁸F]HYAS and [¹⁸F]HYAT) based on a quinone methide (QM) scaffold for non-invasive imaging of H₂O₂ in the brain. Both tracers can respond to H₂O₂ by forming a QM intermediate, which rapidly reacts with nucleophiles. [¹⁸F]HYAT, with proper physicochemical properties, is able of crossing the blood-brain barrier. Increased uptake of [¹⁸F]HYAT was observed in the brains of mice treated with 1-methyl-4-phenyl- l,2,3,6-tetrahydropyridine (MPTP), indicating that [¹⁸F]HYAT is a useful tracer for PET imaging of H₂O₂ in the brain.

Keywords

H₂O₂-responsive / Self-immobilizing / ¹⁸F-labeled tracer / PET imaging / Neurodegenerative diseases / Reactive oxygen species / Radiopharmaceuticals / Bioimaging

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH