3.18.2008




HOW CAN WE IMAGE GLUCOSE METABOLISM?
Fluro-deoxy-glucose (FDG) is an analog of glucose that is labeled to the radioactive positron emitter Flourine-18. The FDG is injected intravenously and is taken up by normal and tumor cells alike in a fashion similar to glucose. In fact, FDG and glucose actively compete with each other for cellular uptake and transport using the GLUT transporters.
When within a cell FDG will be converted into FDG-6- phosphate under the action of hexokinase. The pattern of uptake and phosphorylation being identical for both glucose and FDG. Beyond this point however their pathways diverge, whereas glucose is converted into either energy or stored as glycogen, FDG undergoes no further reaction and by in large remains trapped in the cell. FDG is a radioactive substance and emits radioactive particles called positrons (see Chapter 10 for a basic description of the physics involved in PET/CT and a brief mention of some other positron emitters and their possible medical usage). FDG has a half-life of approximately two hours, meaning that the amount of radioactivity within the body will halve every two hours. Practically speaking. this means that approximately 3% of injected activity will remain in the patient after 10 hours (or 5 half-lives). The distribution of radioactivity within the body can be imaged using a specialized camera called a PET scanner. The resultant image gives a picture of the areas of the body which have FDG (and therefore glucose) uptake. The intense accumulation of FDG within many tumor cells allows those cells to be identified when compared to the less intense uptake in normal cells. Patients are imaged in the fasting state because most normal cells will continue to use free fatty acids as their energy substrate. FDG will primarily be taken up into tumor cells as these cells often lack the ability to effectively use other substrates for energy production (see Figure 1.2). Figure 1.2 is a PET scan showing the normal distribution of glucose (as identified by FDG uptake). This image is called the maximum intensity projection image or MIP and is the 2 dimensional representation of the accumulation of FDG uptake in the body as a whole. The appearances are sometimes likened to that of a glass man. We can see that the brain has intense uptake, with less marked uptake in the heart, liver, and spleen. What we also see is intense uptake in the renal system, kidneys, ureters, and bladder. As you will be aware, normal individuals do not excrete glucose through the renal system, but FDG is excreted renally. We must remember that FDG is not glucose; it is only an analogue of glucose, and it is handled in a different way than normal glucose. Whereas most normal glucose is freely filtered within the renal glomeruli and rapidly reabsorbed by the nephron, the FDG filtered is poorly reabsorbed and a large proportion is excreted in the urine. FIGURE 1.2. The distribution of FDG within a normal individual (MIP).

Top Tip
FDG distribution reflects the glucose metabolism in the body (except for the renal system).

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