title: Diffusion of hyperpolarized (13) C-metabolites in tumor cell spheroids using real-time NMR spectroscopy.
abstract: 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.
authors.affiliation: Institute of Medical Engineering, Technische Universität München, Garching, Germany. fschilling@tum.de
authors.forename: Franz
authors.initials: F
authors.lastname: Schilling
authors.forename: Stephan
authors.initials: S
authors.lastname: Düwel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Köllisch
authors.forename: Markus
authors.initials: M
authors.lastname: Durst
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Schulte
authors.forename: Steffen J
authors.initials: SJ
authors.lastname: Glaser
authors.forename: Axel
authors.initials: A
authors.lastname: Haase
authors.forename: Angela M
authors.initials: AM
authors.lastname: Otto
authors.forename: Marion I
authors.initials: MI
authors.lastname: Menzel
mesh_terms: D002247:Carbon Isotopes; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D004058:Diffusion; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019289:Pyruvic Acid / Q000378:metabolism; D018874:Spheroids, Cellular
chemical_list: D002247:Carbon Isotopes; D019289:Pyruvic Acid