Does Tumor FDG-PET Avidity Represent Enhanced Glycolytic Metabolism in Non-Small Cell Lung Cancer?

Background: In non-small cell lung cancer (NSCLC), ¹⁸fluoro-2-deoxyglucose–positron emission tomography (FDG-PET) assists in diagnosis, staging, and evaluating treatment response. One variable of FDG-PET, the maximum standard uptake value (SUV_m), is considered an objective measure of glucose uptake. However, little is known about the fate of glucose in FDG-avid lung tumors in vivo. This study used stable glucose isotope tracing to determine whether the SUV_m predicts glycolytic metabolism or other glucose fates in tumors. Methods: In this prospective Institutional Review Board-approved clinical trial, 52 untreated potentially resectable confirmed NSCLC patients underwent FDG-PET computed tomography. During the surgical procedure, the patients were infused with ¹³C-labeled glucose. Blood, tumor, and normal lung samples were analyzed by mass spectrometry to determine ¹³C enrichment in glycolytic intermediates. These values were compared with clinical variables, including SUV_m, maximum tumor diameter, stage, grade, and MIB-1/Ki67 proliferation index. Results: For each patient, ¹³C enrichment in each metabolite was compared between tumor and adjacent lung. Although all tumors metabolized glucose, SUV_m did not correlate with glycolytic intermediate labeling. Rather, SUV_m correlated with markers indicating the use of other respiratory substrates, including lactate, and with the proliferation index. Conclusions: SUV_m does not correlate with glycolytic metabolism in human NSCLC but does correlate with the proliferation index, suggesting that SUV_m predicts glucose use by pathways other than glycolysis. These pathways may offer alternative therapeutic targets, including biosynthetic pathways required for cell proliferation. The research techniques in this study offer the opportunity to understand the relationships between SUV_m, tumor metabolism, and therapeutic vulnerabilities in human NSCLCs.