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Identification of Intracellular and Extracellular Metabolites in Cancer Cells Using 13C Hyperpolarized Ultrafast Laplace NMR
journal contribution
posted on 2018-08-20, 00:00 authored by Guannan Zhang, Susanna Ahola, Mathilde H. Lerche, Ville-Veikko Telkki, Christian HiltyUltrafast
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 pyruvate
to 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 predominantly
in 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.
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Keywords
exchange processesExtracellular Metabolites2 D relaxationpyruvatecell metabolitessensitivity13 C Hyperpolarized Ultrafast Laplace NMR Ultrafast Laplace NMRCancer CellsT 2 relaxation timespolarization stepgradient strengthcell metabolismdiffusion coefficientsangle diffusion methodsexperiment timeUF-LNMR methodscanultrafast conceptLNMR experimentsextracellular poolT 2 contrastlactatemouse 4 T 1 cancer cellshyperpolarized UF-LNMRvs intracellular locationdiffusion measurementsD-DNP
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