Direct Monitoring of -Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized 13C-Labeled Molecular Probe

The -glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, -Glu-[1-C-13]Gly, for monitoring GGT activity invivo by hyperpolarized (HP) C-13 magnetic resonance (MR). The properties of -Glu-[1-C-13]Gly are suitable for invivo HP C-13 metabolic analysis since the chemical shift between -Glu-[1-C-13]Gly and its metabolic product, [1-C-13]Gly, is large (4.3ppm) and the T-1 of both compounds is relatively long (30s and 45s, respectively, in H2O at 9.4T). We also demonstrate that -Glu-[1-C-13]Gly is highly sensitive to invivo modulation of GGT activity induced by the inhibitor acivicin.