J Cancer 2017; 8(15):3078-3085. doi:10.7150/jca.20250
Hyperpolarized 13C Diffusion MRS of Co-Polarized Pyruvate and Fumarate to Measure Lactate Export and Necrosis
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.
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
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.