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Diffusion of hyperpolarized 13C-metabolites in tumor cell spheroids using real-time NMR spectroscopy

The detection of tumors noninvasively, the characterization of their progression by defined markers and the monitoring of response to treatment are goals of medical imaging techniques. In this article, a method which measures the apparent diffusion coefficients (ADCs) of metabolites using hyperpolar...

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Bibliographic Details
Published in:NMR in biomedicine 2013-05, Vol.26 (5), p.557-568
Main Authors: Schilling, Franz, Düwel, Stephan, Köllisch, Ulrich, Durst, Markus, Schulte, Rolf F., Glaser, Steffen J., Haase, Axel, Otto, Angela M., Menzel, Marion I.
Format: Article
Language:English
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Summary:The detection of tumors noninvasively, the characterization of their progression by defined markers and the monitoring of response to treatment are goals of medical imaging techniques. In this article, a method which measures the apparent diffusion coefficients (ADCs) of metabolites using hyperpolarized 13C diffusion‐weighted spectroscopy is presented. A pulse sequence based on the pulsed gradient spin echo (PGSE) was developed that encodes both kinetics and diffusion information. In experiments with MCF‐7 human breast cancer cells, we detected an ADC of intracellularly produced lactate of 1.06 ± 0.15 µm2/ms, which is about one‐half of the value measured with pyruvate in extracellular culture medium. When monitoring tumor cell spheroids during progressive membrane permeabilization with Triton X‐100, the ratio of lactate ADC to pyruvate ADC increases as the fraction of dead cells increases. Therefore, 13C ADC detection can yield sensitive information on changes in membrane permeability and subsequent cell death. Our results suggest that both metabolic label exchange and 13C ADCs can be acquired simultaneously, and may potentially serve as noninvasive biomarkers for pathological changes in tumor cells. Copyright © 2012 John Wiley & Sons, Ltd. We have demonstrated that hyperpolarized 13C diffusion‐weighted spectroscopy is feasible. For the first time, apparent diffusion coefficients (ADCs) of 13C‐metabolites could be measured in real time in cells. As a new technique, 13C ADCs can also provide information on the viability of tumor cells. An increase in the ADClac/ADCpyr ratio correlated with the fraction of dead cells, so that these metabolite ADCs are good indicators of necrosis, making them useful tools to monitor the pathological state of tumors in vivo.
ISSN:0952-3480
1099-1492
DOI:10.1002/nbm.2892