Work

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

Year: 2018

Type: article

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.

Source: ACS Sensors

DOI: 10.1021/acssensors.8b01097