Intraoperative arteriovenous patient sampling to assess in situ non–small cell lung cancer metabolism

Abstract We performed intraoperative arteriovenous sampling in participants undergoing surgical resection for non-small cell lung cancer (NSCLC) to characterize in situ tumor metabolism, directly measuring metabolite consumption and secretion in tumor-bearing lung versus normal lung and the systemic circulation. Healthy lung tissue secreted lower levels of lactate, pyruvate, and tricarboxylic acid (TCA) intermediates and consumed less glucose compared to the systemic circulation. In contrast, tumor-bearing lung demonstrated elevated lactate secretion, along with increased efflux of succinate, fumarate, glycine, and aspartate, despite similar glucose uptake. Lactate secretion correlated with tumor PET avidity but not size, and overall metabolic profiles distinguished cancerous from normal lung tissue. These findings confirm enhanced glycolysis in NSCLC in vivo, while also revealing context-dependent patterns of TCA metabolite accumulation and amino acid secretion. Our results demonstrate the utility of intraoperative sampling to uncover metabolic features of human tumors.