Abstract
(13)C Magnetic resonance imaging of hyperpolarized (HP) (13)C-enriched bicarbonate (H(13)CO(3)(-)) and carbon dioxide ((13)CO(2)) is a novel and sensitive technique for tissue pH mapping in vivo. Administration of the HP physiological buffer pair is attractive, but poor polarization and the short T(1) of (13)C-enriched inorganic bicarbonate salts are major drawbacks for this approach. Here, we report a new class of mixed anhydrides for esterase-catalyzed production of highly polarized (13)CO(2) and H(13)CO(3)(-) in tissue. A series of precursors with different alkoxy and acyl groups were synthesized and tested for chemical stability and T(1). (13)C-enriched ethyl acetyl carbonate ((13)C-EAC) was found to be the most suitable candidate due to the relatively long T(1) and good chemical stability. Our results showed that (13)C-EAC can be efficiently and rapidly polarized using BDPA. HP (13)C-EAC was rapidly hydrolyzed by esterase to (13)C-enriched monoacetyl carbonate ((13)C-MAC), which then decomposed to HP (13)CO(2). Equilibrium between the newly produced (13)CO(2) and H(13)CO(3)(-) was quickly established by carbonic anhydrase, producing a physiological buffer pair with (13)C NMR signals that can be quantified for pH measurements. Finally, in vivo tissue pH measurements using HP (13)C-EAC was successfully demonstrated in the liver of healthy rats. These results suggest that HP (13)C-EAC is a novel imaging probe for in vivo pH measurements.