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An increase in dopamine turnover has been shown to occur early in Parkinson's disease (PD). This study investigated changes of dopamine turnover as a function of PD duration using the effective distribution volume (EDV) for dopamine, determined by positron emission tomography with 6-[ 18 F]-fluoro-L-dopa, and compared them with changes in dopamine synthesis and storage ability, quantified with the fluorodopa uptake rate constant K i . Six healthy subjects, 9 early PD patients (PD1), and 13 advanced PD patients (PD2) participated in the study. In the caudate, the K i  and EDV for PD1 were not significantly different from the normal values, whereas in the putamen K i  was 63% of normal and EDV was only 35%. Between PD1 and PD2 the decline in EDV was higher than that for K i  (caudate 44% and putamen 46% for EDV vs. 21% and 34%, respectively, for K i ). Turnover was higher in the caudate than the putamen in controls, whereas the PD patients exhibited the reverse pattern. This comparison of changes in K i  and EDV as a function of disease progression indicates that a relatively slower decrease in dopamine synthesis and a relatively faster increase in turnover in early disease likely act as compensatory mechanisms, and that the clinical onset of PD reflects a global failure of dopaminergic compensatory mechanisms.

journal of cerebral blood flow and metabolism

Changes of Dopamine Turnover in the Progression of Parkinson's Disease as Measured by Positron Emission Tomography: Their Relation to Disease-Compensatory Mechanisms