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Near-simultaneous intravital microscopy of glucose uptake and mitochondrial membrane potential, key endpoints that reflect major metabolic axes in cancer.

Publication ,  Journal Article
Zhu, C; Martinez, AF; Martin, HL; Li, M; Crouch, BT; Carlson, DA; Haystead, TAJ; Ramanujam, N
Published in: Sci Rep
October 23, 2017

While the demand for metabolic imaging has increased in recent years, simultaneous in vivo measurement of multiple metabolic endpoints remains challenging. Here we report on a novel technique that provides in vivo high-resolution simultaneous imaging of glucose uptake and mitochondrial metabolism within a dynamic tissue microenvironment. Two indicators were leveraged; 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) reports on glucose uptake and Tetramethylrhodamine ethyl ester (TMRE) reports on mitochondrial membrane potential. Although we demonstrated that there was neither optical nor chemical crosstalk between 2-NBDG and TMRE, TMRE uptake was significantly inhibited by simultaneous injection with 2-NBDG in vivo. A staggered delivery scheme of the two agents (TMRE injection was followed by 2-NBDG injection after a 10-minute delay) permitted near-simultaneous in vivo microscopy of 2-NBDG and TMRE at the same tissue site by mitigating the interference of 2-NBDG with normal glucose usage. The staggered delivery strategy was evaluated under both normoxic and hypoxic conditions in normal tissues as well as in a murine breast cancer model. The results were consistent with those expected for independent imaging of 2-NBDG and TMRE. This optical imaging technique allows for monitoring of key metabolic endpoints with the unique benefit of repeated, non-destructive imaging within an intact microenvironment.

Duke Scholars

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 23, 2017

Volume

7

Issue

1

Start / End Page

13772

Location

England

Related Subject Headings

  • Phantoms, Imaging
  • Organometallic Compounds
  • Mice, Nude
  • Mice
  • Membrane Potential, Mitochondrial
  • Mammary Neoplasms, Animal
  • Intravital Microscopy
  • Glucose
  • Female
  • Deoxyglucose
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhu, C., Martinez, A. F., Martin, H. L., Li, M., Crouch, B. T., Carlson, D. A., … Ramanujam, N. (2017). Near-simultaneous intravital microscopy of glucose uptake and mitochondrial membrane potential, key endpoints that reflect major metabolic axes in cancer. Sci Rep, 7(1), 13772. https://doi.org/10.1038/s41598-017-14226-x
Zhu, Caigang, Amy F. Martinez, Hannah L. Martin, Martin Li, Brian T. Crouch, David A. Carlson, Timothy A. J. Haystead, and Nimmi Ramanujam. “Near-simultaneous intravital microscopy of glucose uptake and mitochondrial membrane potential, key endpoints that reflect major metabolic axes in cancer.Sci Rep 7, no. 1 (October 23, 2017): 13772. https://doi.org/10.1038/s41598-017-14226-x.
Zhu, Caigang, et al. “Near-simultaneous intravital microscopy of glucose uptake and mitochondrial membrane potential, key endpoints that reflect major metabolic axes in cancer.Sci Rep, vol. 7, no. 1, Oct. 2017, p. 13772. Pubmed, doi:10.1038/s41598-017-14226-x.
Zhu C, Martinez AF, Martin HL, Li M, Crouch BT, Carlson DA, Haystead TAJ, Ramanujam N. Near-simultaneous intravital microscopy of glucose uptake and mitochondrial membrane potential, key endpoints that reflect major metabolic axes in cancer. Sci Rep. 2017 Oct 23;7(1):13772.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 23, 2017

Volume

7

Issue

1

Start / End Page

13772

Location

England

Related Subject Headings

  • Phantoms, Imaging
  • Organometallic Compounds
  • Mice, Nude
  • Mice
  • Membrane Potential, Mitochondrial
  • Mammary Neoplasms, Animal
  • Intravital Microscopy
  • Glucose
  • Female
  • Deoxyglucose