Hyperpolarized 15 N 2 -Diazirine-Tagged MRI Probe for Monitoring γ-Glutamyl Transferase Activity

作者：Eni Minerali, Mai T. Huynh, Hyejin Park, Jun Chen, Sasanka Wathukara Dewege, Joseph K. Park, Joseph K. Park, Zohreh Erfani, Michael E. Chirgwin, Emily R. Derbyshire, Jae Mo Park, Jae Mo Park, Qiu Wang · 发表于：ACS Sensors · 年份：2026 · DOI：10.1021/acssensors.5c04477 · 被引用次数：1 · 研究领域：Sulfur Compounds in Biology、Advanced NMR Techniques and Applications、Electron Spin Resonance Studies

The enzyme γ-glutamyl transferase (GGT) plays an important role in redox homeostasis and is overexpressed in many different cancers. The ability to assess GGT activity provides critical insights into cancer prognosis and pathology. Here, we present a novel imaging agent, ( 15 N) 2 -DT-GG-PA, for in vivo assessment of GGT activity by hyperpolarized nitrogen-15 magnetic resonance imaging (HP 15 N MRI). This 15 N-labeled HP MRI probe is developed by introducing a long-lasting HP ( 15 N) 2 -diazirine tag to deliver essential properties for in vivo detection of GGT activity. Our studies show a large chemical shift difference (Δδ = 6.3 ppm) between ( 15 N) 2 -DT-GG-PA and its product, ( 15 N) 2 -DT-PA, and long HP lifetimes of both compounds ( T 1 = 196 and 81 s, respectively, at 1 T). We also demonstrate the in vivo feasibility of detecting GGT activity using HP ( 15 N) 2 -DT-GG-PA in rat kidneys on a clinical 3 T MRI scanner. Finally, the success of ( 15 N) 2 -DT-GG-PA highlights the transformative potential of the 15 N-tagging approach in designing novel HP 15 N MRI probes beyond structural restrictions for 15 N-isotope labeling.