Molecular Imaging of the Tumor Microenvironment Reveals the Relationship between Tumor Oxygenation, Glucose Uptake, and Glycolysis in Pancreatic Ductal Adenocarcinoma

Abstract

Molecular imaging approaches for metabolic and physiological imaging of tumors have become important for treatment planning and response monitoring. However, the relationship between the physiological and metabolic aspects of tumors is not fully understood. Here, we developed new hyperpolarized MRI and EPR imaging procedures that allow more direct assessment of tumor glycolysis and oxygenation status quantitatively. We investigated the spatial relationship between hypoxia, glucose uptake, and glycolysis in three human pancreatic ductal adenocarcinoma tumor xenografts with differing physiological and metabolic characteristics. At the bulk tumor level, there was a strong positive correlation between 18F-FDG PET and lactate production, while pO2 was inversely related to lactate production and 18F-FDG uptake. However, metabolism was not uniform throughout the tumors, and the whole tumor results masked different localizations that became apparent while imaging. 18F-FDG uptake negatively correlated with pO2 in the center of the tumor and positively correlated with pO2 on the periphery. In contrast to pO2 and 18F-FDG uptake, lactate dehydrogenase activity was distributed relatively evenly throughout the tumor. The heterogeneity revealed by each measure suggests a multimodal molecular imaging approach can improve tumor characterization, potentially leading to better prognostics in cancer treatment.