1. Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
2. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK
3. Department of Radiology, University of Cambridge, Level 5, Box 219, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK
4. GE Healthcare, The Grove Centre GC/18, White Lion Road, Amersham HP7 9LL, UK
5. Imagnia AB, Box 8225, SE-200 41 Malmö, Sweden
6. These authors contributed equally to this work.
7. Present address: Laboratory of Functional and Molecular Imaging, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1065, USA.

Correspondence to: Kevin M. Brindle^1,2 Correspondence and requests for materials should be addressed to K.M.B. (Email: kmb@mole.bio.cam.ac.uk).

Abstract

As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment¹. Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments^{2, 3}. Here we show that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized bicarbonate (H¹³CO₃^-) and ¹³CO₂ following intravenous injection of hyperpolarized H¹³CO₃^-. The technique was demonstrated in a mouse tumour model, which showed that the average tumour interstitial pH was significantly lower than the surrounding tissue. Given that bicarbonate is an endogenous molecule that can be infused in relatively high concentrations into patients⁴, we propose that this technique could be used clinically to image pathological processes that are associated with alterations in tissue pH, such as cancer, ischaemia and inflammation.

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