PMID- 28630930
OWN - NLM
STAT- MEDLINE
DCOM- 20190701
LR  - 20190701
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 3
IP  - 6
DP  - 2017 Jun
TI  - Real-time quantitative analysis of metabolic flux in live cells using a 
      hyperpolarized micromagnetic resonance spectrometer.
PG  - e1700341
LID - 10.1126/sciadv.1700341 [doi]
LID - e1700341
AB  - 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.
FAU - Jeong, Sangmoo
AU  - Jeong S
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
FAU - Eskandari, Roozbeh
AU  - Eskandari R
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
FAU - Park, Sun Mi
AU  - Park SM
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
AD  - Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Alvarez, Julio
AU  - Alvarez J
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
FAU - Tee, Sui Seng
AU  - Tee SS
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
FAU - Weissleder, Ralph
AU  - Weissleder R
AD  - Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, 
      USA.
AD  - Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.
AD  - Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA.
FAU - Kharas, Michael G
AU  - Kharas MG
AUID- ORCID: 0000-0002-1165-6991
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
AD  - Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Lee, Hakho
AU  - Lee H
AUID- ORCID: 0000-0002-0087-0909
AD  - Center for Systems Biology, Massachusetts General Hospital, Boston, MA 02114, 
      USA.
AD  - Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.
FAU - Keshari, Kayvan R
AU  - Keshari KR
AD  - Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
AD  - Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, 
      NY 10065, USA.
AD  - Weill Cornell Medical College, New York, NY 10065, USA.
LA  - eng
GR  - R00 EB014328/EB/NIBIB NIH HHS/United States
GR  - R21 CA205322/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R21 CA212958/CA/NCI NIH HHS/United States
GR  - R01 HL113156/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170616
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - *Energy Metabolism/drug effects
MH  - Humans
MH  - Magnetic Resonance Spectroscopy/*methods
MH  - Neoplasms/metabolism
MH  - Neoplastic Stem Cells/metabolism
MH  - Sensitivity and Specificity
PMC - PMC5473678
OTO - NOTNLM
OT  - Cancer metabolism
OT  - Hyperpolarization
OT  - Leukemia stem cells
OT  - Nuclear magnetic resonance
OT  - metabolic flux
OT  - microfluidics
EDAT- 2017/06/21 06:00
MHDA- 2019/07/02 06:00
PMCR- 2017/06/16
CRDT- 2017/06/21 06:00
PHST- 2017/02/01 00:00 [received]
PHST- 2017/04/26 00:00 [accepted]
PHST- 2017/06/21 06:00 [entrez]
PHST- 2017/06/21 06:00 [pubmed]
PHST- 2019/07/02 06:00 [medline]
PHST- 2017/06/16 00:00 [pmc-release]
AID - 1700341 [pii]
AID - 10.1126/sciadv.1700341 [doi]
PST - epublish
SO  - Sci Adv. 2017 Jun 16;3(6):e1700341. doi: 10.1126/sciadv.1700341. eCollection 2017 
      Jun.