Transmembrane pH imaging distinguishes glycolytic and oxidative phenotypes in gliomas

Motivation: Glycolytic tumor phenotypes upregulate some transmembrane transporters to export H+/lactate, while oxidative phenotypes upregulate other transporters to increase H+/lactate uptake from the tumor niche for their metabolic needs (called "metabolic symbiosis"). Distinguishing between glycolytic and oxidative phenotypes could help design more efficient therapies that target both phenotypes. Goal(s): To use transmembrane pH gradient (ΔpH) imaging to distinguish between glycolytic and oxidative GBM phenotypes. Approach: pHi and pHe imaging were used to measure ΔpH in rat brains with U87 tumors. Results: Our measurements indicate that the glycolytic phenotype is localized in the tumor core while oxidative phenotype is localized at tumor periphery. Impact: Transmembrane pH gradient imaging can be used to distinguish between glycolytic and oxidative tumor phenotypes in glioblastoma. This technique could help design more efficient therapies, where targeting both phenotypes might be more effective than individually targeting each phenotype.