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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2017
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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. |
format | Online Article Text |
id | pubmed-5473678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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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