Real-Time in Vivo Detection of H₂O₂ Using Hyperpolarized ¹³C-Thiourea

Reactive oxygen species (ROS) are essential cellular metabolites widely implicated in many diseases including cancer, inflammation, and cardiovascular and neurodegenerative disorders. Yet, ROS signaling remains poorly understood, and their measurements are a challenge due to high reactivity and instability. Here, we report the development of ¹³C-thiourea as a probe to detect and measure H₂O₂ dynamics with high sensitivity and spatiotemporal resolution using hyperpolarized ¹³C magnetic resonance spectroscopic imaging. In particular, we show ¹³C-thiourea to be highly polarizable and to possess a long spin-lattice relaxation time (T₁), which enables real-time monitoring of ROS-mediated transformation. We also demonstrate that ¹³C-thiourea reacts readily with H₂O₂ to give chemically distinguishable products in vitro and validate their detection in vivo in a mouse liver. This study suggests that ¹³C-thiourea is a promising agent for noninvasive detection of H₂O₂ in vivo. More broadly, our findings outline a viable clinical application for H₂O₂ detection in patients with a range of diseases.