Premium
Diffusion of hyperpolarized 13 C‐metabolites in tumor cell spheroids using real‐time NMR spectroscopy
Author(s) -
Schilling Franz,
Düwel Stephan,
Köllisch Ulrich,
Durst Markus,
Schulte Rolf F.,
Glaser Steffen J.,
Haase Axel,
Otto Angela M.,
Menzel Marion I.
Publication year - 2013
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.2892
Subject(s) - spheroid , chemistry , extracellular , nuclear magnetic resonance , nuclear magnetic resonance spectroscopy , effective diffusion coefficient , kinetics , intracellular , hyperpolarization (physics) , membrane permeability , diffusion , biophysics , membrane , analytical chemistry (journal) , biochemistry , in vitro , magnetic resonance imaging , chromatography , medicine , biology , physics , quantum mechanics , radiology , organic chemistry , thermodynamics
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 13 C 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 µm 2 /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, 13 C ADC detection can yield sensitive information on changes in membrane permeability and subsequent cell death. Our results suggest that both metabolic label exchange and 13 C ADCs can be acquired simultaneously, and may potentially serve as noninvasive biomarkers for pathological changes in tumor cells. Copyright © 2012 John Wiley & Sons, Ltd.