title: Probing lactate secretion in tumours with hyperpolarised NMR.
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.
authors.affiliation: IMETUM, Technische Universität München, Garching, Germany.|GE Global Research, Garching, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Durst
authors.affiliation: IMETUM, Technische Universität München, Garching, Germany.|GE Global Research, Garching, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koellisch
authors.affiliation: University of Torino, Turin, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Daniele
authors.affiliation: Institute of Pathology, TU München, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Steiger
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik,Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: IMETUM, Technische Universität München, Garching, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Haase
authors.affiliation: GE Global Research, Garching, Germany.
authors.forename: Marion I
authors.initials: MI
authors.lastname: Menzel
authors.affiliation: GE Global Research, Garching, Germany.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Schulte
authors.affiliation: University of Torino, Turin, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.affiliation: University of Torino, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Reineri
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D019344:Lactic Acid / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D015336:Molecular Probe Techniques; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D019344:Lactic Acid; D019289:Pyruvic Acid
keywords: Gd chelate based contrast agents; breast cancer; hyperpolarised C-13; spectroscopic imaging