Fig. 1.

Truncated TCA cycle and [¹⁸F]FSPG accumulation in cancer cells. As part of the truncated TCA cycle, L-glutamine is taken up via the ASCT2 transporter. L-glutamine is subsequently processed by GLS into L-glutamate, which is then used by the TCA cycle or transported out of the cell by the system x_C- transporter in exchange for L-cystine in a rate-limiting fashion. [¹⁸F]FSPG biologically functions as L-cystine and is internalized by the system x_C− transporter. This provides precursors for glutathione biosynthesis and, thus, redox maintenance. GLS glutaminase, GSH1 gamma-glutamyl cysteine synthetase, GSH2 glutathione synthase, ROS reactive oxygen species.