Abstract
This chapter presents results from positron emission tomography (PET) scans in rhesus monkeys using a dihydroxyphenylalanine (DOPA) analog, which is not catecholic and not methylated, and therefore has much higher specific-to-nonspecific activity in PET studies of the brain. This allows the delineation of areas of small concentrations of dopaminergic neurons and terminals. Because of the decarboxylating enzyme that acts on DOPA, 18F-6-fluoro-L-DOPA (FDOPA), and 18F-6-fluoro-meta-tyrosine (FMT) present in all catecholaminergic and serotonergic neurons, small concentrations of nondopaminergic neurons are also demonstrated. This tracer may be particularly useful in the evaluation of diseases, such as schizophrenia, that involve extrastriatal dopamine systems. Dopamine is the dominant monoaminergic neurotransmitter in the striatum, and dopaminergic neurons may be responsible for much of the limbic, diencephalic, and mesencephalic uptake as well. However, the presence of specific FMT uptake diffusely through the brain stem, including large areas without dopaminergic cell bodies or terminals, demonstrates accumulation in other monoamine neurons. Lack of the 3-O-methyl metabolite after FMT administration will markedly simplify dopaminergic PET scans performed for the evaluation of the nigrostriatal system in patients with movement disorders. More striking, however, is the possibility that smaller concentrations of extrastriatal Dopaminergic terminals may be now measurable in vivo by PET, which may be important in studying diseases such as schizophrenia. Even the “confounding” specific accumulation of FMT in nondopaminergic neurons may find eventual scientific or clinical use. Studies should be carried out soon to assess both the chemoarchitectural features and potential clinical significance of this tracer in the human brain.
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