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Novel imaging agent detects GGT activity in vivo, suggesting improved cancer prognosis assessment.
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, (¹⁵N)₂-DT-GG-PA, for in vivo assessment of GGT activity by hyperpolarized nitrogen-15 magnetic resonance imaging (HP ¹⁵N MRI). This ¹⁵N-labeled HP MRI probe is developed by introducing a long-lasting HP (¹⁵N)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 (¹⁵N)₂-DT-GG-PA and its product, (¹⁵N)₂-DT-PA, and long HP lifetimes of both compounds (T₁ = 196 and 81 s, respectively, at 1 T). We also demonstrate the in vivo feasibility of detecting GGT activity using HP (¹⁵N)₂-DT-GG-PA in rat kidneys on a clinical 3 T MRI scanner. Finally, the success of (¹⁵N)₂-DT-GG-PA highlights the transformative potential of the ¹⁵N-tagging approach in designing novel HP ¹⁵N MRI probes beyond structural restrictions for ¹⁵N-isotope labeling.
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Minerali et al. (2026) studied this question.
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