TY - JOUR
T1 - Real-Time in Vivo Detection of H2O2 Using Hyperpolarized 13C-Thiourea
AU - Wibowo, Arif
AU - Park, Jae Mo
AU - Liu, Shie Chau
AU - Khosla, Chaitan
AU - Spielman, Daniel M.
N1 - Funding Information:
This work was supported by NIH grants R01 EB019018, DK063158, S10 OD012283, and P41 EB015891; DOD CDMRP PC100427; the Gambhir-RSL grant; and the Stanford BioX program
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/7/21
Y1 - 2017/7/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85025172527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85025172527&partnerID=8YFLogxK
U2 - 10.1021/acschembio.7b00130
DO - 10.1021/acschembio.7b00130
M3 - Article
C2 - 28452454
AN - SCOPUS:85025172527
SN - 1554-8929
VL - 12
SP - 1737
EP - 1742
JO - ACS Chemical Biology
JF - ACS Chemical Biology
IS - 7
ER -