Certain neutron-poor isotopes, for example, ¹¹C and ¹⁸F, are very short-lived (about 20 and 103 min, respectively) and decay by converting protons into neutrons. In the process, positrons (positively-charged electrons) are produced. Positrons are a form of antimatter. When a positron meets an electron, both are annihilated and gamma-ray photons are produced that move away from the point of annihilation in exactly opposite directions.

When such an experiment is carried out in biological tissue, annihilation occurs very close to the point of positron emission. The point of annihilation, and therefore the location of the positron source, can be precisely located by gamma-ray detectors surrounding the experiment. Such an experiment is called positron emission tomography; or PET. Because the radioisotopes are so short-lived and are used at very low levels, they pose no significant threat to the subject.

Imagine that a drug known to have some effect on brain function is chemically “tagged” with one of these positron-emitting isotopes and injected into a patient; the precise location of the drug in the brain can be determined by a PET experiment. A number of drugs have been prepared and used in PET experiments to study brain biochemistry. For example, localization of ¹¹C-cocaine was determined under various dosing conditions (1).

The PET technique was applied to an effort to understand addiction to smoking (enzyme monoamine oxidase-B (MAO-B). MAO-B is involved in the breakdown of dopamine, which is, in turn, implicated in reinforcing and motivating behaviors. They found that the brains of living smokers show a 40% decrease in the level of this enzyme.

The synthesis and purification of compounds using radioisotopes with short half-lives is an art in itself that requires careful “orchestration” and rehearsal with unlabeled compounds. If the synthesis is not performed quickly enough, the radioisotope, and thus the PET-imaging capability, disappears. The radioisotope and the labeled compound to be used are prepared immediately before the PET experiment and used on the spot.

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