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Isotope Production

Positron decaying materials are needed to form a PET image. In the 1950s mostly O-15 and Ga-68 bound to water, carbon dioxide or Ga-ATP were used. From 1976 F-18, N-13 and C-11 isotopes have also been used. The development of medical cyclotrons, i.e. cyclotrons that produce isotopes used specifically as tracers in radiopharmaceuticals, started in the 1980s.

The most commonly used PET isotope used in practice is F-18. This isotope is produced from O-18 by a cyclotron. Since it is a general tracer molecule, it is chemically bound to glucose, this way it becomes the so-called FDG (fluorodeoxyglucose).
Usually negative H ions are accelerated in the cyclotrons, since it is easy to make particles exit the circular orbit (they lose their electrons when they pass through a foil made of a suitable alloy, thus they leave their circular orbit). When the production of F-18 is completed, it is sent to a chemistry laboratory in underground pipes, which are properly shielded for radiation protection reasons, where F-18 is bound to glucose. This process is carried out by semi-automatic synthesizing machines (see figure below) and experts.

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Figure 1 Semi-automatic syntesizing machnie (from PET Center Debrecen University)

 
The synthesis is a very complex process (see figure below).

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FDG synthesis ( from Positron Diagnostic Ltd. education material )

 
The radiopharmaceutical that is created needs to be treated with appropriate radiation protection. Furthermore, a sample of every produced portion has to undergo quality control. A dose calibrator measures the dose of pharmaceutical to be injected into the patient by an automatic injection machine (~10 mCi = 370 MBq per patient). It takes an hour for the right isotope distribution to form, the examination can be started afterwards. Since tumours take up more nutrients than healthy tissue does, they will consume more of the glucose analogue FDG molecule as well. This way FDG accumulates in the tumours, which thus glow in PET images. Owing to the special formulation of FDG, it can penetrate the cells from the blood as a glucose analogue, but after penetration the cell cannot carry out the next step of catabolism. In this respect FDG is not a glucose analogue anymore, thus the cell cannot break it down and dispose of it, so it stays in the cell; that is why it is visible in the image. FDG is excreted from the blood by the kidneys, therefore the bladder always glows in PET images and so does the brain, since glucose is the primary source of energy for the brain.

The most frequently used PET isotopes, their half lives and their method of production are shown below.

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