Metabolic Imaging of Glutamine in Cancer

Glucose and glutamine are the most abundant nutrients for producing energy and building blocks in normal and tumor cells. Increased glycolysis in tumors, the Warburg Effect, is the basis for ¹⁸F-FDG PET imaging. Cancer cells can also be genetically reprogrammed to use glutamine. 5-¹¹C-(2S)-glutamine and ¹⁸F-(2S,4R)4-fluoroglutamine may be useful complementary tools to measure changes in tumor metabolism. In glioma patients, the tracer ¹⁸F-(2S,4R)4-fluoroglutamine showed tumor-to-background contrast different from that of ¹⁸F-FDG and differences in uptake in glioma patients with clinical progression of disease versus stable disease (tumor-to-brain ratio > 3.7 in clinically active glioma tumors, minimal or no specific uptake in clinically stable tumors). These preliminary results suggest that ¹⁸F-(2S,4R)4-fluoroglutamine PET may be a new tool for probing in vivo metabolism of glutamine in cancer patients and for guiding glutamine-targeted therapeutics. Further studies of uptake mechanism, and comparison of kinetics for ¹⁸F-(2S,4R)4-fluoroglutamine versus the ¹¹C-labeled native glutamine, will be important and enlightening.