University of Oulu

Guannan Zhang, Susanna Ahola, Mathilde H. Lerche, Ville-Veikko Telkki, and Christian Hilty (2018) Identification of Intracellular and Extracellular Metabolites in Cancer Cells Using 13C Hyperpolarized Ultrafast Laplace NMR, Analytical Chemistry 2018 90 (18), 11131-11137 DOI: 10.1021/acs.analchem.8b03096

Identification of intracellular and extracellular metabolites in cancer cells using ¹³C hyperpolarized ultrafast laplace NMR

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Author: Zhang, Guannan1,2; Ahola, Susanna3; Lerche, Mathilde H.4;
Organizations: 1Department of Chemistry, Texas A&M University, 3255 TAMU, College Station, Texas 77843, United States
2Guannan Zhang, Department of Chemistry, Duke University, Durham, North Carolina 27708, United States
3NMR Research Unit, Faculty of Science, University of Oulu, P.O. Box 3000, 90014 Oulu, Finland
4Department of Electrical Engineering, Center for Hyperpolarization in Magnetic Resonance, Technical University of Denmark, Building 349, DK-2800 Kgs Lyngby, Denmark
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: American Chemical Society, 2018
Publish Date: 2018-10-12


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 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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Series: Analytical chemistry
ISSN: 0003-2700
ISSN-E: 1520-6882
ISSN-L: 0003-2700
Volume: 90
Issue: 18
Pages: 11131 - 11137
DOI: 10.1021/acs.analchem.8b03096
Type of Publication: A1 Journal article – refereed
Field of Science: 114 Physical sciences
116 Chemical sciences
Funding: We acknowledge the generous support provided by the European Research Council (ERC) under Horizon 2020 (H2020/2018-2022/ERC grant agreement no. 772110), the Academy of Finland (grant numbers 289649 and 294027), the National Science Foundation (Grant CHE-1362691), the Ji and Li Family Foundation, and the Welch Foundation (Grant A-1658).
EU Grant Number: (772110) UFLNMR - Ultrafast Laplace NMR
Academy of Finland Grant Number: 289649
Detailed Information: 289649 (Academy of Finland Funding decision)
294027 (Academy of Finland Funding decision)
Copyright information: © ACS 2018. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.