HyperpolarizedC Diffusion MRS of Co-Polarized Pyruvate and Fumarate to Measure Lactate Export and Necrosis.

Feuerecker, Benedikt; Durst, Markus; Michalik, Michael; Schneider, Günter; Saur, Dieter; Menzel, Marion; Schwaiger, Markus; Schilling, Franz

doi:10.7150/jca.20250

2017

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Dokumenttyp:: Journal Article; 15
Autor(en):: Feuerecker, Benedikt; Durst, Markus; Michalik, Michael; Schneider, Günter; Saur, Dieter; Menzel, Marion; Schwaiger, Markus; Schilling, Franz
Titel:: HyperpolarizedC Diffusion MRS of Co-Polarized Pyruvate and Fumarate to Measure Lactate Export and Necrosis.
Abstract:: Non-invasive tumor characterization and monitoring are among the key goals of medical imaging. Using hyperpolarizedC-labelled metabolic probes fast metabolic pathways can be probed in real-time, providing new opportunities for tumor characterization. In thisstudy, we investigated whether measurement of apparent diffusion coefficient (ADC) measurements and magnetic resonance spectroscopy (MRS) of co-polarizedC-labeled pyruvic acid and fumaric acid can non-invasively detect both necrosis and changes in lactate export, which are parameters indicative of tumor aggressiveness.C-labeled pyruvic acid and fumaric acid were co-polarized in a preclinical hyperpolarizer and the dissolved compounds were added to prepared samples of 8932 pancreatic cancer and MCF-7 breast carcinoma cells. Extracellular lactate concentrations and cell viability were measured in separate assays.The mean ratios of the ADC values of lactate and pyruvate (ADC/ADCbetween MCF-7 (0.533 ± 0.015, n = 3) and 8932 pancreatic cancer cells (0.744 ± 0.064, n = 3) showed a statistically significant difference (p = 0.048). 8932 cells had higher extracellular lactate concentrations in the extracellular medium (22.97 ± 2.53 ng/µl) compared with MCF-7 cells (7.52 ± 0.59 ng/µl; p < 0.001). Fumarate-to-malate conversion was only detectable in necrotic cells, thereby allowing clear differentiation between necrotic and viable cells.We provide evidence that MRS of hyperpolarizedC-labelled pyruvic acid and fumaric acid, with their respective conversions to lactate and malate, are useful for characterization of necrosis and lactate efflux in tumor cells.
Zeitschriftentitel:: J Cancer
Jahr:: 2017
Band / Volume:: 8
Heft / Issue:: 15
Seitenangaben Beitrag:: 3078-3085
Sprache:: eng
Volltext / DOI:: doi:10.7150/jca.20250
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/28928899
Print-ISSN:: 1837-9664
TUM Einrichtung:: II. Medizinische Klinik und Poliklinik (Gastroenterologie); Klinik und Poliklinik für Nuklearmedizin
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