[11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors.
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 micrograms) 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 [11C]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.
Antonini
A
A
PET Department, Paul Scherrer Institute, Villigen, Switzerland.
Schwarz
J
J
Oertel
W H
WH
Beer
H F
HF
Madeja
U D
UD
Leenders
K L
KL
D000328:Adult; D000368:Aged; D000818:Animals; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008090:Lisuride / Q000627:therapeutic use; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012457:Salicylamides / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D007980:Levodopa; D008090:Lisuride