Dataset Information

PHIP hyperpolarized [1-¹³C]pyruvate and [1-¹³C]acetate esters via PH-INEPT polarization transfer monitored by ¹³C NMR and MRI.

ABSTRACT: Parahydrogen-induced polarization of ¹³C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-¹³C]acetate and [1-¹³C]pyruvate esters with application of PH-INEPT-type pulse sequences for ¹H to ¹³C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in ¹³C polarization values of 0.66?±?0.04% and 0.19?±?0.02% for allyl [1-¹³C]pyruvate and ethyl [1-¹³C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for ¹H to ¹³C polarization transfer (3.95?±?0.05% and 0.65?±?0.05% for allyl [1-¹³C]pyruvate and ethyl [1-¹³C]acetate, respectively). Nevertheless, a significant ¹³C NMR signal enhancement with respect to thermal polarization allowed us to perform ¹³C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications.

SUBMITTER: Svyatova A

PROVIDER: S-EPMC7952547 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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PHIP hyperpolarized [1-13C]pyruvate and [1-13C]acetate esters via PH-INEPT polarization transfer monitored by 13C NMR and MRI.

Svyatova Alexandra A Kozinenko Vitaly P VP Chukanov Nikita V NV Burueva Dudari B DB Chekmenev Eduard Y EY Chen Yu-Wen YW Hwang Dennis W DW Kovtunov Kirill V KV Koptyug Igor V IV

Scientific reports 20210311 1

Parahydrogen-induced polarization of 13C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-13C]acetate and [1-13C]pyruvate esters with application of PH-INEPT-type pulse sequences for 1H to 13C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolariza ...[more]

PMID: 33707497

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Project description:The detection and treatment monitoring of inflammatory states remain challenging in part due to the multifactorial mechanisms of immune activation and spectrum of clinical manifestations. Currently, diagnostic strategies tend to be subjective and limited quantitative tools exist to monitor optimal treatment strategies. Pro-inflammatory M1 polarized macrophages exhibit a distinct metabolic glycolytic phenotype compared to the continuum of M2 polarization states. In the present study, the distinct metabolic phenotypes of resting and activated macrophages were successfully characterized and quantified using hyperpolarized carbon-13 (13C) labeled pyruvate and its metabolic products, i.e. lactate, as a biomarker of resting, disease and treated states. Methods: Mouse macrophage J774A.1 cells were used as a model system in an NMR compatible bioreactor to facilitate dynamic hyperpolarized 13C measurements. The glycolytic metabolism of the cells in the quiescent or resting state were compared with macrophages stimulated by lipopolysaccharide, a classical M1 activator using hyperpolarized 13C labeled pyruvate. Additionally, the activated macrophages were also treated with a non-steroidal anti-inflammatory drug to assess the changes in hyperpolarized lactate signal. The hyperpolarized lactate signals were then correlated using biochemical and molecular assays. Results: We first validated our model system of inflammatory cells by the hallmarks of M1 polarization using steady state metabolic profiling with high resolution NMR in conjunction with nitric oxide Greiss assay, enzyme activity, and mRNA expression. Subsequently, we clearly showed that the cutting edge technology of hyperpolarized 13C NMR can be used to detect elevated lactate levels in M1 polarized macrophages in comparison to control and non-steroidal anti-inflammatory drug treated M2 states. Conclusion: Hyperpolarized 13C lactate has the potential to serve as a biomarker to non-invasively detect and quantify pro-inflammatory state of immune regulatory cells and its response to therapy.

Dataset Information

PHIP hyperpolarized [1-¹³C]pyruvate and [1-¹³C]acetate esters via PH-INEPT polarization transfer monitored by ¹³C NMR and MRI.

Publications

PHIP hyperpolarized [1-<sup>13</sup>C]pyruvate and [1-<sup>13</sup>C]acetate esters via PH-INEPT polarization transfer monitored by <sup>13</sup>C NMR and MRI.

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