J Cancer 2017; 8(15):3078-3085. doi:10.7150/jca.20250

Research Paper

Hyperpolarized 13C Diffusion MRS of Co-Polarized Pyruvate and Fumarate to Measure Lactate Export and Necrosis

Benedikt Feuerecker1, 5✉, Markus Durst2, 3, Michael Michalik1, Günter Schneider4, Dieter Saur4, 5, Marion Menzel3, Markus Schwaiger1, Franz Schilling1

1. Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany;
2. Institute of Medical Engineering, Technische Universität München, Garching, Germany;
3. GE Global Research, Munich, Germany;
4. Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Garching, Germany;
5. German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

Background: Non-invasive tumor characterization and monitoring are among the key goals of medical imaging. Using hyperpolarized 13C-labelled metabolic probes fast metabolic pathways can be probed in real-time, providing new opportunities for tumor characterization. In this in vitro study, we investigated whether measurement of apparent diffusion coefficient (ADC) measurements and magnetic resonance spectroscopy (MRS) of co-polarized 13C-labeled pyruvic acid and fumaric acid can non-invasively detect both necrosis and changes in lactate export, which are parameters indicative of tumor aggressiveness.

Methods: 13C-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.

Results: The mean ratios of the ADC values of lactate and pyruvate (ADClac/ADCpyr) between 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.

Conclusion: We provide evidence that MRS of hyperpolarized 13C-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.

Keywords: Hyperpolarization, diffusion-weighted magnetic resonance spectroscopy, lactate export, tumor metabolism.

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How to cite this article:
Feuerecker B, Durst M, Michalik M, Schneider G, Saur D, Menzel M, Schwaiger M, Schilling F. Hyperpolarized 13C Diffusion MRS of Co-Polarized Pyruvate and Fumarate to Measure Lactate Export and Necrosis. J Cancer 2017; 8(15):3078-3085. doi:10.7150/jca.20250. Available from http://www.jcancer.org/v08p3078.htm