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Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer

Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or “fluxes” of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact c...

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Autores principales: Jeong, Sangmoo, Eskandari, Roozbeh, Park, Sun Mi, Alvarez, Julio, Tee, Sui Seng, Weissleder, Ralph, Kharas, Michael G., Lee, Hakho, Keshari, Kayvan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473678/
https://www.ncbi.nlm.nih.gov/pubmed/28630930
http://dx.doi.org/10.1126/sciadv.1700341
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author Jeong, Sangmoo
Eskandari, Roozbeh
Park, Sun Mi
Alvarez, Julio
Tee, Sui Seng
Weissleder, Ralph
Kharas, Michael G.
Lee, Hakho
Keshari, Kayvan R.
author_facet Jeong, Sangmoo
Eskandari, Roozbeh
Park, Sun Mi
Alvarez, Julio
Tee, Sui Seng
Weissleder, Ralph
Kharas, Michael G.
Lee, Hakho
Keshari, Kayvan R.
author_sort Jeong, Sangmoo
collection PubMed
description Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or “fluxes” of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials. However, because of their limited sensitivity, these methods require a larger number of cells, on the order of 10(7), which is impractical for analyzing scant target cells or mass-limited samples. We present a new technology platform, a hyperpolarized micromagnetic resonance spectrometer (HMRS), that achieves real-time, 10(3)-fold more sensitive metabolic analysis on live cells. This platform enables quantification of the metabolic flux in a wide range of cell types, including leukemia stem cells, without significant changes in viability, which allows downstream molecular analyses in tandem. It also enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients. We further advanced this platform for high-throughput analysis of hyperpolarized molecules by integrating a three-dimensionally printed microfluidic system. The HMRS platform holds promise as a sensitive method for studying metabolic dynamics in mass-limited samples, including primary cancer cells, providing novel therapeutic targets and an enhanced understanding of cellular metabolism.
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spelling pubmed-54736782017-06-19 Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer Jeong, Sangmoo Eskandari, Roozbeh Park, Sun Mi Alvarez, Julio Tee, Sui Seng Weissleder, Ralph Kharas, Michael G. Lee, Hakho Keshari, Kayvan R. Sci Adv Research Articles Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or “fluxes” of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials. However, because of their limited sensitivity, these methods require a larger number of cells, on the order of 10(7), which is impractical for analyzing scant target cells or mass-limited samples. We present a new technology platform, a hyperpolarized micromagnetic resonance spectrometer (HMRS), that achieves real-time, 10(3)-fold more sensitive metabolic analysis on live cells. This platform enables quantification of the metabolic flux in a wide range of cell types, including leukemia stem cells, without significant changes in viability, which allows downstream molecular analyses in tandem. It also enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients. We further advanced this platform for high-throughput analysis of hyperpolarized molecules by integrating a three-dimensionally printed microfluidic system. The HMRS platform holds promise as a sensitive method for studying metabolic dynamics in mass-limited samples, including primary cancer cells, providing novel therapeutic targets and an enhanced understanding of cellular metabolism. American Association for the Advancement of Science 2017-06-16 /pmc/articles/PMC5473678/ /pubmed/28630930 http://dx.doi.org/10.1126/sciadv.1700341 Text en Copyright © 2017, The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Jeong, Sangmoo
Eskandari, Roozbeh
Park, Sun Mi
Alvarez, Julio
Tee, Sui Seng
Weissleder, Ralph
Kharas, Michael G.
Lee, Hakho
Keshari, Kayvan R.
Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
title Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
title_full Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
title_fullStr Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
title_full_unstemmed Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
title_short Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
title_sort real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473678/
https://www.ncbi.nlm.nih.gov/pubmed/28630930
http://dx.doi.org/10.1126/sciadv.1700341
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