Design and Characterization of Hyperpolarized ¹⁵N-BBCP as a H₂O₂-Sensing Probe

Abstract

Hydrogen peroxide (H2O2) is a type of reactive oxygen species that regulates essential biological processes. Despite the central role of H2O2 in pathophysiological states, available molecular probes for assessing H2O2 in vivo are still limited. This work develops hyperpolarized 15N-boronobenzyl-4-cyanopyridinium (15N-BBCP) as a rationally designed molecular probe for detecting H2O2. The 15N-BBCP demonstrated favorable physicochemical and biochemical properties for H2O2 detection and dynamic nuclear polarization, allowing noninvasive detection of H2O2. In particular, 15N-BBCP and the products possessed long spin–lattice relaxation times and spectrally resolvable 15N chemical shift differences. The performance of hyperpolarized 15N-BBCP was demonstrated both in vitro and in vivo with time-resolved 15N-MRS. This study highlights a promising approach to designing a reaction-based 15N-labeled molecular imaging agent for detecting oxidative stress in vivo.

Hyperpolarization of 15N‐Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies

“…After hyperpolarization with pH 2 and subsequent polarization transfer from 1 H to 15 N, hyperpolarized H 2 O 2 sensor 15 N-BBSP would be formed. Based on previous literature reports, [19,22] we envisioned that a phenol intermediate 15 N-hydroxybenzyl-2styrylpyridinium ( 15 N-HBSP) can be released via oxidation with H 2 O 2 . Then a base-assisted 1,6 elimination/rearrangement of 15 N-HBSP was expected to take place and delivered 15 N-2-styrylpyridin ( 15 N-SP) as well as quinone methide-d 2 (QM-d 2 ).…”

“…[14,18] Notably, Park et al disclosed a d-DNP 15 N-boronobenzyl-4-cyanopyridinium as a reaction-based H 2 O 2 -sensing probe, demonstrating the great potential of hyperpolarized 15 N-probes for oxidative stress in MR imaging wherein a 15 N-labelled nitrogen serves as a reporter group. [19] All existing hyperpolarized ROS sensors use d-DNP strategies. There are currently no known PHIP ROS sensors.…”

Hyperpolarization of 15N‐Pyridinium by Using Parahydrogen Enables Access to Reactive Oxygen Sensors and Pilot In Vivo Studies

“…[14,18] Notably, Park et al disclosed a d-DNP 15 N-boronobenzyl-4-cyanopyridinium as a reaction-based H 2 O 2 -sensing probe, demonstrating the great potential of hyperpolarized 15 N-probes for oxidative stress in MR imaging wherein a 15 N-labelled nitrogen serves as a reporter group. [19] All existing hyperpolarized ROS sensors use d-DNP strategies. There are currently no known PHIP ROS sensors.…”