What does reduced FDG uptake mean in high-grade gliomas?

Purpose: As well as in many others cancers, FDG uptake is correlated with the degree of malignancy in gliomas, that is, commonly high FDG uptake in high-grade gliomas. However, in clinical practice, it is not uncommon to observe high-grade gliomas with low FDG uptake. Our aim was to explore the tumor metabolism in 2 populations of high-grade gliomas presenting high or low FDG uptake. Methods: High-resolution magic-angle spinning nuclear magnetic resonance spectroscopy was realized on tissue samples from 7 high-grade glioma patients with high FDG uptake and 5 high-grade glioma patients with low FDG uptake. Tumor metabolomics was evaluated from 42 quantified metabolites and compared by network analysis. Results: Whether originating from astrocytes or oligodendrocytes, the highgrade gliomas with low FDG avidity represent a subgroup of high-grade gliomas presenting common characteristics: low aspartate, glutamate, and creatine levels, which are probably related to the impaired electron transport chain in mitochondria; high serine/glycine metabolism and so one-carbon metabolism; low glycerophosphocholine-phosphocholine ratio in membrane metabolism, which is associated with tumor aggressiveness; and finally negative MGMT methylation status. Conclusions: It seems imperative to identify this subgroup of high-grade gliomas with low FDG avidity, which is especially aggressive. Their identification could be important for early detection for a possible personalized treatment, such as antifolate treatment.