Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom.
Wellcome Centre for Integrative Neuroimaging (WIN), Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Cancer Res. 2019 Apr 1;79(7):1343-1352. doi: 10.1158/0008-5472.CAN-18-2168. Epub 2019 Jan 24.
Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors. Combining APT MRI measurements with histological measurements of protein concentration in a rat model of brain metastasis, we determined that the proportion of APT MRI signal originating from changes in protein concentration was approximately 66%, with the remaining 34% originating from changes in tumor pH. In a mouse model of hypopharyngeal squamous cell carcinoma (FaDu), APT MRI showed that a reduction in tumor hypoxia was associated with a shift in tumor pH. The results of this study extend our understanding of APT MRI data and may enable the use of APT MRI to infer the pH of individual patients' tumors as either a biomarker for therapy stratification or as a measure of therapeutic response in clinical settings. SIGNIFICANCE: These findings advance our understanding of amide proton transfer magnetic resonance imaging (APT MRI) of tumors and may improve the interpretation of APT MRI in clinical settings.
异常的 pH 值是恶性肿瘤的一个常见特征，临床上与治疗效果不佳有关。酰胺质子转移磁共振成像（APT MRI）有望成为一种非侵入性测量肿瘤 pH 值的方法，但多种因素共同使从 APT MRI 数据中定量测量肿瘤 pH 值变得具有挑战性。本研究旨在提高我们对肿瘤中 APT MRI 信号改变的生物物理来源的理解。我们将 APT MRI 测量与脑转移大鼠模型中蛋白质浓度的组织学测量相结合，确定 APT MRI 信号中源自蛋白质浓度变化的比例约为 66%，其余 34%源自肿瘤 pH 值的变化。在小鼠下咽鳞状细胞癌（FaDu）模型中，APT MRI 显示肿瘤缺氧的减少与肿瘤 pH 值的变化有关。本研究的结果扩展了我们对 APT MRI 数据的理解，并可能使 APT MRI 能够推断个体患者肿瘤的 pH 值，作为治疗分层的生物标志物或作为临床治疗反应的衡量标准。意义：这些发现推进了我们对肿瘤酰胺质子转移磁共振成像（APT MRI）的理解，并可能改善临床环境中对 APT MRI 的解释。
