Molecular Imaging of the Tumor Microenvironment Reveals the Relationship between Tumor Oxygenation, Glucose Uptake, and Glycolysis in Pancreatic Ductal Adenocarcinoma
| Autor: | Stephen Adler, Shun Kishimoto, Nallathamby Devasahayam, Nobu Oshima, Elaine M. Jagoda, Rajani Choudhuri, Tomohiro Seki, Kazutoshi Yamamoto, James Mitchell, Keita Saito, Murali Krishna, Jeffrey R. Brender, Peter L. Choyke |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Partial Pressure Glucose uptake Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Fluorodeoxyglucose F18 Cell Line Tumor Lactate dehydrogenase Biomarkers Tumor Tumor Microenvironment medicine Animals Humans Glycolysis Tumor microenvironment Chemistry Electron Spin Resonance Spectroscopy Metabolism Tumor Oxygenation Hypoxia (medical) Molecular Imaging Oxygen Pancreatic Neoplasms Glucose 030104 developmental biology Oncology Positron-Emission Tomography 030220 oncology & carcinogenesis Cancer research Heterografts Radiopharmaceuticals Molecular imaging medicine.symptom Carcinoma Pancreatic Ductal |
| Zdroj: | Cancer Res |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-19-0928 |
| Popis: | 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 18F-FDG-PET and lactate production, while pO2 was inversely related to lactate production and 18F-2-fluoro-2-deoxy-D-glucose (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. 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. |
| Databáze: | OpenAIRE |
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