Imaging pH with hyperpolarized 13C.
- Abstract:
- pH is a fundamental physiological parameter that is tightly controlled by endogenous buffers. The acid-base balance is altered in many disease states, such as inflammation, ischemia and cancer. Despite the importance of pH, there are currently no routine methods for imaging the spatial distribution of pH in humans. The enormous gain in sensitivity afforded by dynamic nuclear polarization (DNP) has provided a novel way in which to image tissue pH using MR, which has the potential to be translated into the clinic. This review explores the advantages and disadvantages of current pH imaging techniques and how they compare with DNP-based approaches for the measurement and imaging of pH with hyperpolarized 13C. Intravenous injection of hyperpolarized 13C-labeled bicarbonate results in the rapid production of hyperpolarized 13CO 2 in the reaction catalyzed by carbonic anhydrase. As this reaction is close to equilibrium in the body and is pH dependent, the ratio of the 13C signal intensities from H 13CO 3- and 13CO 2, measured using MRS, can be used to calculate pH invivo. The application of this technique to a murine tumor model demonstrated that it measured predominantly extracellular pH and could be mapped in the animal using spectroscopic imaging techniques. A second approach has been to use the production of hyperpolarized 13CO 2 from hyperpolarized [1- 13C]pyruvate to measure predominantly intracellular pH. In tissues with a high aerobic capacity, such as the heart, the hyperpolarized [1- 13C]pyruvate undergoes rapid oxidative decarboxylation, catalyzed by intramitochondrial pyruvate dehydrogenase. Provided that there is sufficient carbonic anhydrase present to catalyze the rapid equilibration of the hyperpolarized 13C label between CO 2 and bicarbonate, the ratio of their resonance intensities may again be used to estimate pH, which, in this case, is predominantly intracellular. As both pyruvate and bicarbonate are endogenous molecules they have the potential to image tissue pH in the clinic. © 2011 John Wiley & Sons, Ltd.
- Authors:
- FA Gallagher, MI Kettunen, KM Brindle
- Journal:
- NMR in Biomedicine
- Citation info:
- 24(8):1006-1015
- Publication date:
- 1st Oct 2011
- Full text
- DOI