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Could Sugar replace Gadolinium-Based Contrast Agents used for MRIs?

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Animal studies have shown that D-glucose is a potential biodegradable MRI contrast agent for imaging glucose uptake in tumors.  According to findings reported by Xu et al in “Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients”, dynamic glucose-enhanced (DGE) imaging is feasible in humans.  Chemical exchange saturation transfer (CEST) MRI was used to image dynamic signal changes in the human brain at 7 Tesla (7T) during and after infusion of D-glucose (sugar).

DGE image data from 4 normal volunteers and 3 glioma patients showed strong signal enhancement in blood vessels, while the enhancement varied spatially over the tumor.  The authors noted that the areas of enhancement differed spatially between DGE and conventional Gd-enhanced imaging, suggesting complementary image information content for these two types of agents.

The researchers concluded that it was possible to detect water signal changes in the human brain induced by infusion of D-glucose.  They said that the signal changes are due to glucose uptake in vessels, the brain and tumor tissue areas, and are related to the kinetics of delivery, transport and metabolism of D-glucose.  They noted that an interesting finding is that different tumor areas showed varying times of enhancement, which suggests that the dynamic time curves may contain information about blood-brain barrier (BBB) permeability.

According to the study authors, a larger human study is needed, and for DGE to become relevant clinically, it would have to be possible at 3 Tesla and preferably also at 1.5 Tesla.

Why this is important for patients – 

According to a recent article about the study published on Newswise.com, D-glucose is the first non-metallic, biodegradable, natural MRI contrast agent tested in humans.  This new approach offers a safer alternative to metal complexes, such as gadolinium that are commonly used to enhance MRI images. Gadolinium-based contrast agents can have side effects in patients with impaired kidney function, and retained gadolinium can accumulate in the tissues of people who need repeat MRIs, including those with normal kidneys.

Peter van Zijl, Ph.D., Chief, Neuroscience, Division of MR Research at Johns Hopkins and senior author of the study, is quoted as saying, “It is a significant step to be able to obtain clear MRI images of the brain using a biocompatible substance that is metabolized naturally by the body relatively quickly.”  “The dose of D-glucose is similar to that used for diabetes testing and is much cheaper than the metallic agents.”

Dr. van Zijl explained that the glucose results are even more significant given the recent studies finding gadolinium from gadolinium-based contrast agents deposited in brain and bone.  He is quoted as saying, “These recent published findings are showing that gadolinium deposition in tissue could be more common than previously thought, so the development of a natural contrast agent alternative is certainly a high priority for the imaging community and, of course, patients”.

The good news is that there is existing FDA approval of intravenous D-glucose for other indications such as the glucose tolerance test used daily around the country.  The study authors said that they are in the process of requesting the FDA to approve D-glucose for use as an imaging agent.  In my opinion, that cannot happen soon enough.

Sharon Williams

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Xu, X., Yadav, N. N., Knutsson, L., Hua, J., Kalyani, R., Hall, E., … van Zijl, P. C. M. (2015). Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients. Tomography : A Journal for Imaging Research, 1(2), 105–114. http://doi.org/10.18383/j.tom.2015.00175

Xu, X., Chan, K. W. Y., Knutsson, L., Artemov, D., Xu, J., Liu, G., … van Zijl, P. C. M. (2015). Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer. Magnetic Resonance in Medicine, 74(6), 1556–63. http://doi.org/10.1002/mrm.25995

Newswise, 14-Apr-2016.  Researchers Use Simple Sugar to Detect Human Brain Tumors: Glucose-enhanced MRI provides safer alternative for tumor imaging.  http://www.newswise.com/articles/view/651668/?sc=rsla


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