In Vivo Evaluation of Glutaminase Activity with Hyperpolarized [5-13C,4,4-2H2,5-15N]-L-Glutamine in PDAC
Roozbeh Eskandari1, Arsen Mamakhanyan1, Michelle Saoi2, Kristin L Granlund1, Justin Cross2, Craig B Thompson3, and Kayvan Rahimi Keshari1,4
1Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 2Memorial Sloan Kettering Cancer Center, New York, NY, United States, 3Cancer Biology & Genetics Program Share, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 4Radiology, Memorial Sloan Kettering, New York, NY, United States
We developed a custom-synthesized compound, [5-13C,4,4-2H2,5-15N]-L-Glutamine, as a hyperpolarized MRI probe for glutaminase activity. We were able to detect in vivo conversion of hyperpolarized glutamine to glutamate in murine model of PDAC.
Conversion of [5-13C,4-2H2,5-15N]-L-Glutamine to [5-13C,4-2H2]-L-Glutamate with glutaminase in tumor. Red, orange, blue represent sites of 13C, 2H and 15N enrichment, respectively.
A T2-weighted 1H MRI of mouse, with tumor (right) highlighted as regions of sagittal slab B Dynamic of conversion of glutamine to glutamate in the tumor with vehicle. C Dynamic of conversion of glutamine to glutamate in the tumor with glutaminase inhibitor CB-839