Tumour pH and protein concentration contribute to the signal of amide proton transfer magnetic resonance imaging

Abnormal pH is a common feature of malignant tumours and has been associated clinically with sub-optimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to non-invasively measure tumour pH, yet multiple factors collectively make quantification of tumour 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 tumours. Combining in vivo APT MRI measurements with ex vivo 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 tumour pH. In a mouse model of hypopharyngeal squamous cell carcinoma (FaDu), APT MRI showed that a reduction in tumour hypoxia was associated with a shift in tumour 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' tumours as either a biomarker for therapy stratification or as a measure of therapeutic response in clinical settings.

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