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Tumour glucose uptake and metabolism
Tumours utilise glucose at a higher rate than most other tissues, a phenomenon that is known as the Warburg effect. As most tumours exhibit this effect, it has been suggested as a basis for discriminating them from normal tissues and as a target for therapies. This is the basis of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which uses a form of radioactive glucose to identify tumour deposits in the clinic. However, it is a very expensive technique and the behaviour of the form of glucose used in FDG-PET behaves very differently to normal glucose. Our new technique, named glucose chemical exchange saturation transfer (glucoseCEST, developed in collaboration with Prof. Xavier Golay from the Institute of Neurology) can measure the uptake of normal, unlabelled glucose in tumours using an MRI scanner (see Figure 1).
This approach is potentially much cheaper than FDG-PET and the results of recent experiments suggest that it may allow the metabolism of glucose into breakdown products (e.g. glucose-6-phosphate, fructose) to be measured. We have also investigated the ability to model glucose pharmacokinetics using an accelerated, dynamic glucoseCEST acquisition scheme (see Figure 2).
Figure 1: Top row: Maps of 18F-FDG (a glucose analogue (top row), acquired using autoradiography. Bottom row: Maps of glucose uptake from the same tumours (bottm row), measured using glucoseCEST.
Figure 2: Top: Pharmacokinetic maps from fits to dynamic glucose-enhanced CEST data. Kin is the rate of wash-in of glucose, V is the volume accessible to glucose and AUC is the area under the curve. Bottom: Average raw data and fitted curves from the regions of interest defined in the V parameter map above.
Walker-Samuel S, Ramasawmy R, Torrealdea F, Rega M, Rajkumar V, Johnson SP, Richardson S, Gonçalves M, Parkes HG, Arstad E, Thomas DL, Pedley RB, Lythgoe MF, Golay X. In vivo imaging of glucose uptake and metabolism in tumors. Nature Medicine, 2013 Aug;19(8):1067-72.
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