Magnetic Resonance Spectroscopy Measurements of Glutaminase Activity Using Hyperpolarized 13C-Labeled Glutamine

Detection of abnormal metabolic fluxes or unusual accumulation of metabolites could be used to monitor the predisposition to cancer in humans. Imaging can not only support an initial diagnosis, but also monitor progress in terms of staging, restaging, treatment response, and identification of recurrence, both at the primary tumor and at distant metastatic sites. Due to change in tumor metabolism elevated glutamine cellular uptake and its metabolism may act a marker of tumor growth and cell pro- liferation. Metabolic magnetic resonance imaging with hyperpolarized 13C-labelled substances (13CMMR) allows non–invasive investigation of in vivo metabolism. Using 13CMMR, metabolism of 13C-glutamine can be tracked in vivo in real time and the glutamine accumulation can localize the tumor. While working on [5-13C]glutamine hyperpolarization, fast liquid-state polarization decay during the transfer in Earth’s low magnetic field to the MRI scanner was observed. This behavior could be hypo- thetically explained by substantial T1 shortening due to a relaxation through scalar coupling (type II) of fast-relaxing quadrupolar 14N to adjacent 13C nucleus in the glutamine’s amide group. This contribution is only effective in Earth’s low magnetic fields (> 800 μT) and prevents the use of molecules bearing the 13C-amide group as hyperpolarized MRS/MRI probes. The results show that high hyperpolarization levels can be retained using either a 15N-labeled amide or by applying a strong magnetic field during transfer of the sample from the polarizer to the MRI scanner.