² H MRI-based quantification of leucine uptake in glioblastoma multiforme

Glioblastoma (GBM) brain tumors are among the most lethal of all human cancers, with a median survival time of ∼15 months. Treatment planning requires radiologic demarcation of tumor boundaries with contrast-enhanced magnetic resonance imaging (CE MRI); however, significant tumor burden extends beyond the contrast-enhancing margins of the tumor. GBM tumors have an increased expression of amino acid (AA) transporters, including the Alanine, Serine, Cysteine Transporter 2 (ASCT2) and the L-Type Amino Acid Transporter 1 (LAT1). This upregulation has been leveraged in positron emission tomography (PET) studies to detect tumor burden beyond the contrast-enhancing margins identified by standard-of-care CE MRI. Here we leverage recent approaches in deuterium metabolic magnetic resonance with this known upregulation of AA transporters in GBM to demonstrate that ² H MR can detect glioma based on enhanced branched- chain amino acid (BCAA) uptake. To the best of our knowledge, these data represent the first non- invasive quantification of AA concentrations in brain tumor and raises the potential to (i) detect tumor burden beyond contrast-enhancing margins and (ii) quantify AA metabolism using ² H MR spectroscopy.