Abstract
13C Magnetic resonance imaging of hyperpolarized (HP) 13C-enriched bicarbonate (H13CO3 -) and carbon dioxide (13CO2) 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 T1 of 13C-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 13CO2 and H13CO3 - in tissue. A series of precursors with different alkoxy and acyl groups were synthesized and tested for chemical stability and T1. 13C-enriched ethyl acetyl carbonate (13C-EAC) was found to be the most suitable candidate due to the relatively long T1 and good chemical stability. Our results showed that 13C-EAC can be efficiently and rapidly polarized using BDPA. HP 13C-EAC was rapidly hydrolyzed by esterase to 13C-enriched monoacetyl carbonate (13C-MAC), which then decomposed to HP 13CO2. Equilibrium between the newly produced 13CO2 and H13CO3 - was quickly established by carbonic anhydrase, producing a physiological buffer pair with 13C NMR signals that can be quantified for pH measurements. Finally, in vivo tissue pH measurements using HP 13C-EAC was successfully demonstrated in the liver of healthy rats. These results suggest that HP 13C-EAC is a novel imaging probe for in vivo pH measurements.
Original language | English (US) |
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Pages (from-to) | 2232-2236 |
Number of pages | 5 |
Journal | ACS Sensors |
Volume | 3 |
Issue number | 11 |
DOIs | |
State | Published - Nov 26 2018 |
Keywords
- C MRI
- bicarbonate
- carbon dioxide
- esterase
- ethyl acetyl carbonate
- hyperpolarization
- pH sensor
ASJC Scopus subject areas
- Bioengineering
- Instrumentation
- Process Chemistry and Technology
- Fluid Flow and Transfer Processes