Molecular imaging of system xc- with PET

The cell’s endogenous antioxidant system is critical for maintaining redox homeostasis.

The cytsine/glutamate antiporter, system xC-, controls the balance between intracellular reactive oxygen species and antioxidant production by providing cells with access to cystine, a critical amino acid in glutathione biosynthesis, in exchange for glutamate.

The restricted expression of system xC- in healthy tissue highlights the potential for non-invasive PET imaging of this dynamic process and enable increased understanding of oxidative stress, GSH biosynthesis, and glutamate secretion in a range of diseases such as cancer.

Despite the importance of system xC-, few specific radiopharmaceuticals have been reported, with often little knowledge regarding their cellular fate, tissue-specific properties and disease specificity.Dr.

Beinat’s group at Stanford University, California has recently pioneered the development of a homo-glutamate derivative labeled with fluorine-18 named [18F]hGTS13 as a novel radiotracer targeting system xC-.

The goal of the proposed project is to elucidate the cellular fate and specificity of [18F]hGTS13 in cancer compared to inflammation, as well as to determine the potential of [18F]hGTS13 for monitoring ferroptosis, a new distinct class of regulated cell death and posited to play a major role in cancer related tumor suppression.