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.

中文翻译：

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肿瘤微环境的分子成像揭示了胰管腺癌中肿瘤氧合、葡萄糖摄取和糖酵解之间的关系。


用于肿瘤代谢和生理成像的分子成像方法对于治疗计划和反应监测变得非常重要。然而，肿瘤的生理和代谢方面之间的关系尚未完全了解。在这里，我们开发了新的超极化 MRI 和电子顺磁共振成像程序，可以更直接地定量评估肿瘤糖酵解和氧合状态。我们研究了三种具有不同生理和代谢特征的人胰腺导管腺癌肿瘤异种移植物中缺氧、葡萄糖摄取和糖酵解之间的空间关系。在大块肿瘤水平上，18F-FDG-PET 与乳酸产生之间存在很强的正相关性，而 pO2 与乳酸产生和 18F-2-氟-2-脱氧-D-葡萄糖 (18F-FDG) 摄取呈负相关。然而，整个肿瘤的代谢并不均匀，整个肿瘤结果掩盖了在成像时变得明显的不同定位。 18F-FDG 摄取与肿瘤中心的 pO2 呈负相关，与周围的 pO2 呈正相关。与 pO2 和 18F-FDG 摄取相反，乳酸脱氢酶活性在整个肿瘤中分布相对均匀。每项测量所揭示的异质性表明多模式分子成像方法可以改善肿瘤特征，从而有可能在癌症治疗中带来更好的预后。意义：新型多模式分子成像技术揭示了三种相互关联的成像生物标志物在描绘肿瘤微环境以及缺氧、葡萄糖摄取和糖酵解之间的相互关系方面的潜力。