1. Molecular Imaging of the Tumor Microenvironment Reveals the Relationship between Tumor Oxygenation, Glucose Uptake, and Glycolysis in Pancreatic Ductal Adenocarcinoma.
- Author
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Yamamoto K, Brender JR, Seki T, Kishimoto S, Oshima N, Choudhuri R, Adler SS, Jagoda EM, Saito K, Devasahayam N, Choyke PL, Mitchell JB, and Krishna MC
- Subjects
- Animals, Biomarkers, Tumor metabolism, Carcinoma, Pancreatic Ductal diagnostic imaging, Cell Line, Tumor, Electron Spin Resonance Spectroscopy methods, Fluorodeoxyglucose F18, Glycolysis, Heterografts, Humans, Mice, Molecular Imaging methods, Pancreatic Neoplasms diagnostic imaging, Partial Pressure, Positron-Emission Tomography methods, Radiopharmaceuticals, Tumor Microenvironment, Carcinoma, Pancreatic Ductal metabolism, Glucose metabolism, Oxygen metabolism, Pancreatic Neoplasms metabolism
- Abstract
Molecular imaging approaches for metabolic and physiologic imaging of tumors have become important for treatment planning and response monitoring. However, the relationship between the physiologic and metabolic aspects of tumors is not fully understood. Here, we developed new hyperpolarized MRI and electron paramagnetic resonance 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 physiologic and metabolic characteristics. At the bulk tumor level, there was a strong positive correlation between
18 F-FDG-PET and lactate production, while pO2 was inversely related to lactate production and18 F-2-fluoro-2-deoxy-D-glucose (18 F-FDG) uptake. However, metabolism was not uniform throughout the tumors, and the whole tumor results masked different localizations that became apparent while imaging.18 F-FDG uptake negatively correlated with pO2 in the center of the tumor and positively correlated with pO2 on the periphery. In contrast to pO2 and18 F-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. SIGNIFICANCE: Novel multimodal molecular imaging techniques reveal the potential of three interrelated imaging biomarkers to profile the tumor microenvironment and interrelationships of hypoxia, glucose uptake, and glycolysis., (©2020 American Association for Cancer Research.)- Published
- 2020
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