title: Separation of extra- and intracellular metabolites using hyperpolarized (13)C diffusion weighted MR.
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.
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, CA, USA.
authors.forename: Bertram L
authors.initials: BL
authors.lastname: Koelsch
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA. Electronic address: renuka.sriram@ucsf.edu.
authors.forename: Renuka
authors.initials: R
authors.lastname: Sriram
authors.affiliation: Radiology and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
authors.forename: Kayvan R
authors.initials: KR
authors.lastname: Keshari
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Leon Swisher
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Van Criekinge
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sukumar
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, CA, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Vigneron
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Zhen J
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, CA, USA.
authors.forename: Peder E Z
authors.initials: PEZ
authors.lastname: Larson
authors.affiliation: Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA; UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
mesh_terms: D019149:Bioreactors; D002247:Carbon Isotopes / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D019344:Lactic Acid / Q000032:analysis; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D019289:Pyruvic Acid / Q000032:analysis
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D019289:Pyruvic Acid
keywords: Aerobic glycolysis; Cancer; Cancer aggressiveness; Cellular transport; Diffusion weighted magnetic resonance; Dynamic nuclear polarization (DNP); Hyperpolarized (13)C magnetic resonance (HP (13)C MR); Lactate; Lactate efflux; Pyruvate; Renal cell carcinoma (RCC)