In vivo imaging of glucose uptake and metabolism in tumors using MRI

Tumors have a greater reliance on anaerobic glycolysis for energy production than normal tissues. This key discriminator of tumors from normal tissues has been exploited as a target for anticancer therapy as well in the detection of metastatic disease by FDG-PET. This techniques involves imaging of tumors through monitoring of the uptake of 18Fluoro-deoxy glucose and has been used for many years as a standard method for the measurement of the metabolic activity of tumors. However there are drawbacks to the FDG-PET procedure. In addition to being expensive, FDG-PET of course involves the injection of radioactive tracer. There are also concerns that the behavior of the labelled glucose may be slightly different from that of native glucose.

A research group at the Centre of Advanced Biomedical Imaging (CABI) at University College London (UCL) led by Dr S Walker-Samuel realized that the ability to probe tumor glucose uptake by MRI without the use of radioactive tracers would offer substantial cost reductions relative to FDG-PET and yet still provide important clinical benefits.

The CABI group have developed a noninvasive method for imaging glucose uptake in vivo that is based on magnetic resonance imaging and allows the uptake of unlabeled glucose to be measured through the chemical exchange of protons between hydroxyl groups and water. This method differs from existing molecular imaging methods because it permits detection of the delivery and uptake of a metabolically active compound in physiological quantities. The group has now published their findings (Walker-Samuel S et al. Nature Medicine 2013 Jul 7). These show that the technique, named glucose chemical exchange saturation transfer (glucoCEST), is sensitive to tumor glucose accumulation in colorectal tumor models and can distinguish tumor types with differing metabolic characteristics and pathophysiologies. Dr Walker-Samuel said: “GlucoCEST uses radio waves to magnetically label glucose in the body. This can then be detected in tumours using conventional MRI techniques. The method uses an injection of normal sugar and could offer a cheap, safe alternative to existing methods for detecting tumors, which require the injection of radioactive material.” He added “Conventional MRI images mostly map the signal from water and fat, but we have adapted our scanner to allow the signal from glucose to be amplified, via the water signal. We used the technique called chemical exchange saturation transfer (CEST), which employs the exchange of protons between glucose hydroxyl groups and bulk tissue water protons. By selectively saturating the magnetisation of protons in glucose hydroxyl groups, using radiofrequency pulses, the exchange of protons causes an associated reduction in the signal from water, which we can then map using a standard MRI acquisition. Using colorectal carcinoma xenograft models, we tested out whether this effect was sensitive enough to detect the accumulation of injected glucose in vivo, and to evaluate whether the measured glucose signal corresponded with other gold-standard measures of glucose uptake.

The results of the study suggest that glucoCEST has indeed a high potential as a useful and cost-effective method for characterizing disease and assessing response to therapy in the clinic.