[C-11] RACLOPRIDE AND POSITRON EMISSION TOMOGRAPHY IN PREVIOUSLY UNTREATED PATIENTS WITH PARKINSONS-DISEASE - INFLUENCE OF L-DOPA AND LISURIDE THERAPY ON STRIATAL DOPAMINE D-2-RECEPTORS

We studied cerebral dopamine D-2-receptor binding using [C-11]raclopride and PET in 18 previously untreated patients with Parkinson's disease (PD) and 14 healthy volunteer subjects. Sixteen patients were scanned before and after 3 to 4 months of stable oral therapy with either L-dopa (300 mg/d) (n = 7) or lisuride (0.8 to 1.2 mg/d) (n = 9). Two additional patients were investigated before and after a continuous TV infusion of L-dopa. In addition, we studied the effect of acute N L-dopa and lisuride administration on [C-11]raclopride binding in a healthy rhesus monkey. At baseline, PD patients showed higher uptake values in the putamen than did healthy subjects (p < 0.0001). Oral lisuride treatment lowered [C-11]raclopride uptake in the putamen (-19%) and in the caudate nucleus (-15%) compared with baseline, but the difference did not reach significance upon Bonferroni correction for multiple comparisons. However, putamen tracer uptake returned to baseline in two patients when we repeated [C-11]raclopride scans 4 days after lisuride withdrawal. Oral L-dopa treatment did not induce changes in the putamen or caudate nucleus indices. Acute lisuride (25 mu g) administration in a healthy monkey reduced striatal uptake values, but acute injection of L-dopa (300 mg) did not. The results suggest that lisuride blocks [C-11]raclopride binding at dopamine D-2-receptor sites and demonstrate that 3 to 4 months' oral therapy with L-dopa or lisuride does not change striatal dopamine D-2-receptor density in PD patients.