Dataset Information

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

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.

SUBMITTER: Maptue N

PROVIDER: S-EPMC7593868 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Maptue Nesmine N Jiang Weina W Harrison Crystal C Funk Alexander M AM Sharma Gaurav G Malloy Craig R CR Sherry Dean D Khemtong Chalermchai C

ACS sensors 20181109 11

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 ...[more]

PMID: 30398335

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Project description:L-1-Chloro-4-phenyl-3-tosylamido[1-13C]butan-2-one (Tos-[1-13C]Phe-CH2Cl) and Tos-[1-13C,2H2]Phe-CH2Cl were prepared and used to alkylate delta-chymotrypsin. The relaxation parameters of the 13C-n.m.r. signal resulting from the alkylation of histidine-57 in both enzyme-inhibitor complexes were determined at 1.88 T and 6.34 T as well as the spin-lattice relaxation times of the backbone alpha-carbon atoms of the unenriched Tos-Phe-CH2-delta-chymotrypsin complex. It is concluded that the species examined do not have significant internal librational motions and that the rotational correlation time of the monomeric enzyme-inhibitor complex is 16.0 +/- 3.2 ns. The signal from the 13C-enriched atom of Tos-[1-13C,2H2]Phe-CH2Cl is split into a quintet (JCD = 23 Hz) whereas in the Tos-[1-13C,2H2]Phe-CH2-delta-chymotrypsin complex the signal from the 13C-enriched inhibitor carbon atom is decoupled. This decoupled signal had linewidths of 16 +/- 3 Hz and 52 +/- 2 Hz at 1.88 T and 6.34 T respectively, whereas linewidths at 40 +/- 2 Hz and 53 +/- 4 Hz were obtained for the same signal in the Tos-[1-13C]Phe-CH2-delta-chymotrypsin complex at 1.88 T and 6.34 T respectively. Therefore whereas deuteration produces a 2.5-fold reduction in linewidth at 1.88 T there is no significant decrease in the linewidth at 6.34 T. This result is explained by using the rigid rotor model, which predicts that the quadrupolar spin-lattice relaxation rate will be faster at low field strengths, resulting in more efficient deuterium decoupling by scalar relaxation of the second kind at lower field strengths. It is also predicted that deuterium decoupling by scalar relaxation will become less efficient as rotational correlation times increase. The consequences of these predictions for the detection of 13C-enriched atomic probes of proteins are discussed. It is also shown that a spin-echo pulse sequence can be used to remove signals due to protonated carbon atoms without attenuating the signal due to deuterated carbon atoms.

Dataset Information

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

Publications

Esterase-Catalyzed Production of Hyperpolarized <sup>13</sup>C-Enriched Carbon Dioxide in Tissues for Measuring pH.

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