Probing lactate secretion in tumours with hyperpolarised NMR. (27th June 2016)

• Record Type: Journal Article
• Authors: Durst, Markus; Koellisch, Ulrich; Daniele, Valeria; Steiger, Katja; Schwaiger, Markus; Haase, Axel; Menzel, Marion I.; Schulte, Rolf F.; Aime, Silvio; Reineri, Francesca
• Is Part Of: NMR in biomedicine. Volume 29:Number 8(2016:Aug.)
• Page Start: 1079
• Page End: 1087
• Publication Date: 2016-06-27
• Subjects: hyperpolarised C‐13 -- Gd chelate based contrast agents -- spectroscopic imaging -- breast cancer; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3574
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Most tumours exhibit a high rate of glycolysis and predominantly produce energy by lactic acid fermentation. To maintain energy production and prevent toxicity, the lactate generated needs to be rapidly transported out of the cell. This is achieved by monocarboxylate transporters (MCTs), which therefore play an essential role in cancer metabolism and development. In vivo experiments were performed on eight male Fisher F344 rats bearing a subcutaneous mammary carcinoma after injection of hyperpolarised [1‐ 13 C]pyruvate. A Gd(III)DO3A complex that binds to pyruvate and its metabolites was used to efficiently destroy the extracellular magnetisation after hyperpolarised lactate had been formed. Moreover, a pulse sequence including a frequency‐selective saturation pulse was designed so that the pyruvate magnetisation could be destroyed to exclude effects arising from further conversion. Given this preparation, metabolite transport out of the cell manifested as additional decay and apparent cell membrane transporter rates could thus be obtained using a reference measurement without a relaxation agent. In addition to slice‐selective spectra, spatially resolved maps of apparent membrane transporter activity were acquired using a single‐shot spiral gradient readout. A considerable increase in decay rate was detected for lactate, indicating rapid transport out of the cell. The alanine signal was unaltered, which corresponds to a slower efflux rate. This technique could allow for better understanding of tumour metabolism and progression, and enable treatment response measurements for MCT‐targeted cancer therapies. Moreover, it provides vital insights into the signal kinetics of hyperpolarised [1‐ 13 C]pyruvate examinations. Copyright © 2016 John Wiley & Sons, Ltd. Abstract : A method to directly measure metabolite efflux in vivo using hyperpolarised biomarkers in combination with a tailored relaxation agent is presented. High lactate efflux rates were found in mammary carcinoma bearing rats after injection of hyperpolarised [1‐ 13 C]pyruvate. In addition to slice‐selective spectra, spatially resolved maps of membrane transporter activity could be obtained using frequency‐selective excitation and a single‐shot spiral gradient readout.