Figure 3. Hyperpolarized [1-¹³C] glutamate from hyperpolarized [1-¹³C] α-KG can be detected in vivo in normal brain and in U87IDHwt tumors only.

T2-weighted MR images of (A) a U87IDHwt and (B) a U87IDHmut tumor-bearing animals overlaid with tumor (red) and normal brain (blue) voxels from the 2D CSI acquisition. The tumors appear as hypersignals and are circled with dotted lines. The corresponding hyperpolarized ¹³C MR spectra from tumor and normal brain voxels are shown for both animals. The observed resonances are: (1) hyperpolarized [1-¹³C] glutamate (green arrow, δ_GLU=177.5ppm); (2) hyperpolarized [1-¹³C] α-KG (δ_α-KG=172.6ppm); (3) hyperpolarized [1-¹³C] α-KG hydrate (δ_α-KG-Hyd=180.9ppm). Note the presence of hyperpolarized [1-¹³C] glutamate in normal brain for both animals, but only in the tumor tissue of the U87IDHwt animal. (C) T2-weighted MR images (first column) of the head of a U87IDHwt (top row) and a U87IDHmut (bottom row) tumor-bearing animal overlaid with the grid used for 2D ¹³C CSI acquisition. Corresponding heatmaps of hyperpolarized [1-¹³C] α-KG and hyperpolarized [1-¹³C] glutamate acquired 25 seconds post injection of hyperpolarized [1-¹³C] α-KG. These heatmaps illustrate the presence of hyperpolarized [1-¹³C] glutamate in normal brain and tumor in U87IDHwt animals, and in normal brain only in U87IDHmut animals. (D) Ratio of hyperpolarized [1-¹³C] glutamate to hyperpolarized [1-¹³C] α-KG (integral values) expressed as a percent of the same ratio in normal brain. The normalized glutamate/α-KG ratio is lower in U87IDHmut tumors as compared to U87IDHwt (n=2 per tumor type).