Imaging the Tumor Antioxidant Response with [F]FSPG PET.

(4S)-4-(3-[F]Fluoropropyl)-L-glutamic acid ([F]FSPG) is a flourine-18 labeled glutamate analog that enables the noninvasive in vivo imaging of cellular redox status. [F]FSPG is transported across the cell membrane by the cystine/glutamate antiporter, system x, whose expression is upregulated in multiple cancer types. The requirement of cystine for the biosynthesis of glutathione, a major antioxidant, connects [F]FSPG tissue retention to the intracellular redox response via system x activity. We herein describe the use of [F]FSPG positron emission tomography (PET) to image the tumor antioxidant response and highlight key methodological considerations.