[ ¹¹ C]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 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.

Neuroimaging in Parkinson’s disease

“…71 Serial 11 C-raclopride PET has shown that after 6 months of exposure to levodopa the mildly increased putamen 11 Craclopride binding seen in de novo PD patients subsequently normalizes. 73 Chronically levodopa-exposed PD cases continue to show normal levels of putamen D2 binding, explaining their good locomotor response to levodopa. 74 11 C-SCH23390 PET, a marker of D1 site binding, has revealed normal striatal uptake in de novo PD, 74 whereas patients who had been exposed to levodopa for several years showed a 20% reduction in striatal binding.…”

Positron emission tomography imaging of transplant function

“…After its intravenous administration 18 F-dopa is taken up by the terminals of dopaminergic projections and stored as 18 F-dopamine and its metabolites. 1 The rate of striatal 18 F accumulation reflects both 18 F-dopa transport into striatal dopamine vesicles and its decarboxylation by dopa decarboxylase (DDC).…”

“…After its intravenous administration 18 F-dopa is taken up by the terminals of dopaminergic projections and stored as 18 F-dopamine and its metabolites. 1 The rate of striatal 18 F accumulation reflects both 18 F-dopa transport into striatal dopamine vesicles and its decarboxylation by dopa decarboxylase (DDC). Within the 90 min of a conventional 18 F-dopa PET scan, striatal 18 F uptake can be regarded as essentially unidirectional and so can be represented kinetically by an influx constant, K i .…”

“…1 The rate of striatal 18 F accumulation reflects both 18 F-dopa transport into striatal dopamine vesicles and its decarboxylation by dopa decarboxylase (DDC). Within the 90 min of a conventional 18 F-dopa PET scan, striatal 18 F uptake can be regarded as essentially unidirectional and so can be represented kinetically by an influx constant, K i . 2,3 18 F-dopa PET, coupled with SPM, reveals bilateral loss of 18 F-dopa uptake in puta-men in early hemi-PD patients, dorsal structures being more affected than ventral.…”

“…Within the 90 min of a conventional 18 F-dopa PET scan, striatal 18 F uptake can be regarded as essentially unidirectional and so can be represented kinetically by an influx constant, K i . 2,3 18 F-dopa PET, coupled with SPM, reveals bilateral loss of 18 F-dopa uptake in puta-men in early hemi-PD patients, dorsal structures being more affected than ventral. 4 Reductions of motor cortex and posterior cingulate K i can also be detected.…”