Stimulated Raman scattering: Glucose tracking

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  • Published: Aug 1, 2015
  • Author: David Bradley
  • Channels: Raman
thumbnail image: Stimulated Raman scattering: Glucose tracking

Following glucose

Stimulated Raman scattering (SRS) imaging of glucose uptake activity by targeting the alkyne tag of a novel glucose analogue in live mouse brain hippocampal neurons and tumor tissues (in red). (Credit: Fanghao Hu)

Stimulated Raman scattering (SRS) imaging can be used to follow glucose uptake activity in living cells by using a derivative of the sugar molecule tagged with an alkynyl group. The technique has been demonstrated on live mouse brain hippocampal neurones and tumour tissues.

Fanghao Hu, Zhixing Chen, Luyuan Zhang, Yihui Shen, Lu Wei1 and Wei Min of Columbia University, New York, USA, explain how glucose is a ubiquitous energy source for most living organisms..from bacterium to human. As such, its uptake correlates with cellular metabolic demand, and this activity could be a particularly useful indicator of problems in various physiopathological conditions, such as obesity, diabetes, and cancer. However, radioactive fluorine-18 labelled glucose in positron emission tomography (PET), magnetic resonance imaging (MRI), and fluorescence microscopy can all be used but have limitations that stymie research in various ways. Primarily, none of these techniques has the requisite spatial resolution to visualize glucose uptake down to the single cell level. Min and colleagues have now devised a new research platform to help them visualize this glucose uptake activity in live cells and tissues that disturbs the organism only minimally and yet provides a much clearer view of glucose uptake activity than has been possible previously.

Alkynyl tag

Writing in the journal Angewandte Chemie International Edition, Min's team describe a new glucose analogue that behaves in a similar manner physiologically to natural glucose but the alkynyl moiety appended to the sugar ring allows them to image its uptake as an energy source by living cancer cells, neurons and tissues at the single cell level using SRS. Previously used tags, such as fluorescent labels might have been useful but for the fact that they alter the chemistry of glucose too much and so change the biochemical reaction pathways down which it wends its way once inside the living cell. Moreover, the fluorescent labels themselves are large and so become targets for a whole range of enzymes and the glucose becomes almost an incidental part of the process.

Demanding tissues

The team reported their initial work on coupling SRS with alkyne tags earlier in the year as a general strategy for imaging small biomolecules. An alkyne tag gives rise to a strong and characteristic Raman scattering signal in an otherwise silent spectroscopic region. As such, it can be used with high sensitivity and specificity to generate a quantitative concentration map in three dimensions.

The team has now demonstrated that this technique can distinguish between cancer cell lines having different metabolic activities and can reveal heterogeneous uptake patterns in neurons, mouse brain tissues and tumour tissues with clear cell-to-cell variations. The team points out that the border between tumour proliferating regions and dead tissue, the necrotic region, can be clearly seen at the single cell level through the sharp contrast in glucose uptake activity.

"By offering the distinct advantage of subcellular resolution and avoiding the undesirable influence of fluorescent dyes, we believe our technique can complement FDG in clinical PET imaging for visualizing glucose uptake activity at the cellular level," explains team member Fanghao Hu. Indeed, while the researchers are currently using their approach to image glucose uptake dynamics in mice they hope that it will be useful in human medicine for imaging the brain and malignant tumours both of which have high energy, and therefore glucose, demands.

Related Links

Angew Chem Int Edn 2015, online: "Vibrational Imaging of Glucose Uptake Activity in Live Cells and Tissues by Stimulated Raman Scattering"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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