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Talia Harris1, Galit Eliyahu2, Lucio Frydman1, Hadassa Degani2

1Chemical Physics, Weizmann Institute of Science, Rehovot, Israel; 2Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

The enhanced polarization enabled by ex situ Dynamic Nuclear Polarization may allow us to follow metabolic processes non-invasively with unprecedented sensitivity and temporal resolution. In order to understand the altered metabolism of cancer and screen for additional biomarkers we have developed a perfusion-infusion bioreactor, allowing hyperpolarized metabolic measurements on living cell cultures. In this work we compare the metabolism of 1-13C-Pyruvate and 1-13C-Lactate in breast cancer cells. The kinetic measurements allow us to demonstrate that the metabolism of 1-13C-Lactate is transport limited, as was previously established for 1-13C-Pyruvate.



1024. Modeling of Pyruvate/Lactate Kinetics Using a Two-Site Exchange Model

Aaron Keith Grant1, Elena Vinogradov1, Pankaj K. Seth1, Xiaoen Wang1, Robert E. Lenkinski1, Vikas P. Sukhatme1

1Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States

Hyperpolarized pyruvate undergoes rapid conversion into lactate, alanine, and bicarbonate in vivo. Lactate is of particular interest as elevated lactate levels may serve as a biomarker for cancer. Although lactate SNR has been shown to correlate with histological characteristics of tumors, quantitative measures of kinetics are desirable. We present fits of a simple two-site exchange model to data acquired in an animal model of non-small lung cancer, and show that these methods can quantify reductions in lactate formation rates following administration of dichloroacetate, a drug that up-regulates the activity of pyruvate dehydrogenase.



1025. A Feasibility Study in Mini-Pig for Heart Metabolism with Hyperpolarized [1-13C]pyruvate: MRS Cardiac Modelling and Kinetic Considerations

Francesca Frijia1, Luca Menichetti1, Vincenzo Positano1, Vincenzo Lionetti2, Claudia Forte3, Jan H. Ardenkjaer-Larsen4, Matteo Milanesi1, Giulio Giovannetti1, Daniele De Marchi1, Giovanni Aquaro1, Manuela Campan2, Fabio A. Recchia5, Luigi Landini1, Maria Filomena Santarelli1, Massimo Lombardi1

1MRI Lab, "G. Monasterio" Foundation and Institute of Clinical Physiology, Pisa, Italy; 2Sector of Medicine, Scuola Superiore Sant'Anna, Pisa, Italy; 3Istituto per i Processi Chimico Fisici, CNR,, Pisa, Italy; 4GE Healthcare, Huginsvej 8, 3400 Hillerod,, Denmark; 5Department of Physiology, New York College, Valhalla, New York

Changes in metabolic products of pyruvate can be correlated to the patho-physiological condition of the myocardium: The cardiac oxidation of pyruvate depends on oxygen delivery to myocardium and on the activation state of mitochondrial pyruvate dehydrogenase. The real time tracking of the metabolic fate of pyruvate in the intact heart with MRS would provide a key information on the state of myocardium in response to a variety of stimuli. This study deal with the real time in vivo cardiac metabolism after intravenous injection of hyperpolarized [1-13C]-pyruvate in the animal of mid size with a 3T scanner with regards to the typical kinetic profile of accumulation of each metabolite and if the typical pattern could be modelled with simple equations.



1026. Multiplet Asymmetry and Multi-Spin Order in Liquid-State NMR Spectra of Hyperpolarized Compounds


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