Identification of Intracellular and Extracellular Metabolites in Cancer Cells Using 13C Hyperpolarized Ultrafast Laplace NMR

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

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Identification of Intracellular and Extracellular Metabolites in Cancer Cells Using 13C Hyperpolarized Ultrafast Laplace NMR. / Zhang, Guannan; Ahola, Susanna; Lerche, Mathilde Hauge; Telkki, Ville-Veikko; Hilty, Christian.

In: Analytical chemistry, Vol. 90, No. 18, 2018, p. 11131-11137.

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

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Zhang, Guannan ; Ahola, Susanna ; Lerche, Mathilde Hauge ; Telkki, Ville-Veikko ; Hilty, Christian. / Identification of Intracellular and Extracellular Metabolites in Cancer Cells Using 13C Hyperpolarized Ultrafast Laplace NMR. In: Analytical chemistry. 2018 ; Vol. 90, No. 18. pp. 11131-11137.

Bibtex

@article{128e289f99254cc487efa362a7076bac,
title = "Identification of Intracellular and Extracellular Metabolites in Cancer Cells Using 13C Hyperpolarized Ultrafast Laplace NMR",
abstract = "Ultrafast Laplace NMR (UF-LNMR), which is based on the spatial encoding of multidimensional data, enables one to carry out 2D relaxation and diffusion measurements in a single scan. Besides reducing the experiment time to a fraction, it significantly facilitates the use of nuclear spin hyperpolarization to boost experimental sensitivity, because the time-consuming polarization step does not need to be repeated. Here we demonstrate the usability of hyperpolarized UF-LNMR in the context of cell metabolism, by investigating the conversion of pyruvateto lactate in the cultures of mouse 4T1 cancer cells. We show that 13C ultrafast diffusion–T2 relaxation correlation measurements, with the sensitivity enhanced by several orders of magnitude by dissolution dynamic nuclear polarization (D-DNP), allows the determination of the extra- vs intracellular location of metabolites because of their significantly different values of diffusion coefficients and T2 relaxation times. Under the current conditions, pyruvate was located predominantlyin the extracellular pool, while lactate remained primarily intracellular. Contrary to the small flip angle diffusion methods reported in the literature, the UF-LNMR method does not require several scans with varying gradient strength, and it provides a combined diffusion and T2 contrast. Furthermore, the ultrafast concept can be extended to various other multidimensional LNMR experiments, which will provide detailed information about the dynamics and exchange processes of cell metabolites.",
author = "Guannan Zhang and Susanna Ahola and Lerche, {Mathilde Hauge} and Ville-Veikko Telkki and Christian Hilty",
year = "2018",
doi = "10.1021/acs.analchem.8b03096",
language = "English",
volume = "90",
pages = "11131--11137",
journal = "Analytical Chemistry",
issn = "0003-2700",
publisher = "American Chemical Society",
number = "18",

}

RIS

TY - JOUR

T1 - Identification of Intracellular and Extracellular Metabolites in Cancer Cells Using 13C Hyperpolarized Ultrafast Laplace NMR

AU - Zhang, Guannan

AU - Ahola, Susanna

AU - Lerche, Mathilde Hauge

AU - Telkki, Ville-Veikko

AU - Hilty, Christian

PY - 2018

Y1 - 2018

N2 - Ultrafast Laplace NMR (UF-LNMR), which is based on the spatial encoding of multidimensional data, enables one to carry out 2D relaxation and diffusion measurements in a single scan. Besides reducing the experiment time to a fraction, it significantly facilitates the use of nuclear spin hyperpolarization to boost experimental sensitivity, because the time-consuming polarization step does not need to be repeated. Here we demonstrate the usability of hyperpolarized UF-LNMR in the context of cell metabolism, by investigating the conversion of pyruvateto lactate in the cultures of mouse 4T1 cancer cells. We show that 13C ultrafast diffusion–T2 relaxation correlation measurements, with the sensitivity enhanced by several orders of magnitude by dissolution dynamic nuclear polarization (D-DNP), allows the determination of the extra- vs intracellular location of metabolites because of their significantly different values of diffusion coefficients and T2 relaxation times. Under the current conditions, pyruvate was located predominantlyin the extracellular pool, while lactate remained primarily intracellular. Contrary to the small flip angle diffusion methods reported in the literature, the UF-LNMR method does not require several scans with varying gradient strength, and it provides a combined diffusion and T2 contrast. Furthermore, the ultrafast concept can be extended to various other multidimensional LNMR experiments, which will provide detailed information about the dynamics and exchange processes of cell metabolites.

AB - Ultrafast Laplace NMR (UF-LNMR), which is based on the spatial encoding of multidimensional data, enables one to carry out 2D relaxation and diffusion measurements in a single scan. Besides reducing the experiment time to a fraction, it significantly facilitates the use of nuclear spin hyperpolarization to boost experimental sensitivity, because the time-consuming polarization step does not need to be repeated. Here we demonstrate the usability of hyperpolarized UF-LNMR in the context of cell metabolism, by investigating the conversion of pyruvateto lactate in the cultures of mouse 4T1 cancer cells. We show that 13C ultrafast diffusion–T2 relaxation correlation measurements, with the sensitivity enhanced by several orders of magnitude by dissolution dynamic nuclear polarization (D-DNP), allows the determination of the extra- vs intracellular location of metabolites because of their significantly different values of diffusion coefficients and T2 relaxation times. Under the current conditions, pyruvate was located predominantlyin the extracellular pool, while lactate remained primarily intracellular. Contrary to the small flip angle diffusion methods reported in the literature, the UF-LNMR method does not require several scans with varying gradient strength, and it provides a combined diffusion and T2 contrast. Furthermore, the ultrafast concept can be extended to various other multidimensional LNMR experiments, which will provide detailed information about the dynamics and exchange processes of cell metabolites.

U2 - 10.1021/acs.analchem.8b03096

DO - 10.1021/acs.analchem.8b03096

M3 - Journal article

VL - 90

SP - 11131

EP - 11137

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 18

ER -