[¹¹C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease

Abstract

We studied cerebral dopamine D₂-receptor binding using [¹¹C]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 IV infusion of L-dopa. In addition, we studied the effect of acute IV L-dopa and lisuride administration on [¹¹C]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 [¹¹C]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 [¹¹C]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 μg) 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 [ⁿC]raclopride binding at dopamine D₂-receptor sites and demonstrate that 3 to 4 months' oral therapy with L-dopa or lisuride does not change striatal dopamine D₂-receptor density in PD patients.