Separation of extra- and intracellular metabolites using hyperpolarized 13C diffusion weighted MR

Pyruvate Magnetic Resonance Spectroscopy Biophysics 610 Diffusion weighted magnetic resonance Cell Line 03 medical and health sciences Engineering Bioreactors 0302 clinical medicine Dynamic nuclear polarization Cell Line, Tumor 616 Hyperpolarized (13)C magnetic resonance (HP (13)C MR) Pyruvic Acid Hyperpolarized C-13 magnetic resonance Cellular transport Humans Lactate efflux Lactic Acid Cancer Carbon Isotopes Tumor Magnetic Resonance Imaging Renal cell carcinoma Physical sciences Physical Sciences Cancer aggressiveness Biomedical Imaging Lactate Aerobic glycolysis
DOI: 10.1016/j.jmr.2016.07.002 Publication Date: 2016-07-10T05:02:39Z
ABSTRACT
This work demonstrates the separation of extra- and intracellular components of glycolytic metabolites with diffusion weighted hyperpolarized (13)C magnetic resonance spectroscopy. Using b-values of up to 15,000smm(-2), a multi-exponential signal response was measured for hyperpolarized [1-(13)C] pyruvate and lactate. By fitting the fast and slow asymptotes of these curves, their extra- and intracellular weighted diffusion coefficients were determined in cells perfused in a MR compatible bioreactor. In addition to measuring intracellular weighted diffusion, extra- and intracellular weighted hyperpolarized (13)C metabolites pools are assessed in real-time, including their modulation with inhibition of monocarboxylate transporters. These studies demonstrate the ability to simultaneously assess membrane transport in addition to enzymatic activity with the use of diffusion weighted hyperpolarized (13)C MR. This technique could be an indispensible tool to evaluate the impact of microenvironment on the presence, aggressiveness and metastatic potential of a variety of cancers.
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