Imaging the Tumor Antioxidant Response with [¹⁸F]FSPG PET

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