Brain dopaminergic mechanisms in Parkinson's disease evaluated by positron emission tomography

The meso-striatal dopamine neurons, essential for the automated control of movements, are primarily affected in patients with P.D. Direct study of the role of this pathway in states of disease has not been possible until recently and the application of PET for the in vivo investigation of dopaminergic mechanisms may serve to demonstrate the potential of the technique. One basic idea has been to work out methods to investigate multiple aspects of dopaminergic function, i.e. presynaptic mechanisms such as re-uptake sites and synthesis of neurotransmitter as well as postsynaptic such as receptor properties. Furthermore, efforts have been made to evaluate dopamine degradating enzymes. Preclinical PET-investigations have regularly been performed in Rhesus monkeys and the hemiparkinsonian model produced by infusing MPTP into one internal carotid artery has been of great value to characterize new 11C-labelled tracers. Today 11C--(+)-nomifensine is used to give a measure of dopamine re-uptake sites, probably reflecting nerve terminals. 11C-labelled L-dopa has now been introduced and can be expected to replace 18F-L-fluorodopa as a physiological tracer for precursor transport and transmitter synthesis. Several ligands are available for the quantitation of dopamine receptors--11C-N-methylspiperone and 11C-raclopride have been used in our studies. 11C-L-selegiline and its "inactive" D-form have been used in clinical PET-studies aimed to evaluate the enzyme MAO-B. A summary of in vivo information of dopaminergic mechanisms in P.D. obtained using the above-mentioned tracers and PET is presented.