Imaging the master regulator of the antioxidant response in non-small cell lung cancer with positron emission tomography.

ABSTRACT: Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. The cystine/glutamate antiporter, system x_c^-, is one of the >200 cytoprotective proteins controlled by NRF2, which can be non-invasively imaged by (S)-4-(3-¹⁸F-fluoropropyl)-l-glutamate ([¹⁸F]FSPG) positron emission tomography (PET). Through genetic and pharmacologic manipulation, we show that [¹⁸F]FSPG provides a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC. We validate imaging readouts with metabolomic measurements of system x_c^- activity and their coupling to intracellular glutathione concentration. A re

SUBMITTER: Greenwood HE 

PROVIDER: S-EPMC10760199 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature