Esterase-Catalyzed Production of Hyperpolarized 13C-Enriched Carbon Dioxide in Tissues for Measuring pH

Nesmine Maptue, Weina Jiang, Crystal Harrison, Alexander M. Funk, Gaurav Sharma, Craig R Malloy, Dean Sherry, Chalermchai Khemtong

Research output: Contribution to journalArticle

2 Scopus citations

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 languageEnglish (US)
Pages (from-to)2232-2236
Number of pages5
JournalACS Sensors
Volume3
Issue number11
DOIs
StatePublished - Nov 26 2018

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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

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