Fig. 2.

Hyperpolarized [1-¹³C] lactate production is not elevated in mutant IDH1 glioma tumors in vivo, in contrast to results in GBM tumors, and is associated with low LDHA and MCT4 expression (A) T2-weighted MR images of BT142 (left) and U87 (right) tumor bearing mice and positioning of tumor voxels (U87 red; BT142 blue). The tumor is circled in dashed lines. Corresponding stack plot of hyperpolarized ¹³C MR spectra obtained at 14.1 Tesla following intravenous injection of hyperpolarized [1-¹³C] pyruvate (δ = 172.9 ppm). Production of hyperpolarized [1-¹³C] lactate could be detected in both tumor types at δ = 185 ppm, although the levels of hyperpolarized [1-¹³C] lactate was lower in BT142 tumors as compared to U87. The color spectra represent the sum of the spectra over time (U87 red; BT142 blue). (B) Kinetics of hyperpolarized (HP) lactate normalized to maximum pyruvate in U87 (red, n = 5) and a BT142 (blue, n = 5) tumor voxels. (C) Analysis of the ratios of hyperpolarized [1-¹³C] lactate-to-pyruvate AUC in tumor voxels demonstrates the significantly lower level of hyperpolarized [1-¹³C] lactate production in BT142 tumors as compared to U87 (*p < 0.05). (D) Western blots for lactate dehydrogenase A (LDHA), monocarboxylate transporters 1 and 4 (MCT1, MCT4) for BT142 and U87 tumor lysates and (E) corresponding protein levels expressed as % of U87 (**p < 0.01; ***p < 0.005). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)