Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study.
OBJECTIVE
To evaluate the relationship between clinical improvement and in vivo synaptic dopamine (DA) release after a single oral dose of levodopa (LD) in patients with advanced Parkinson disease (PD).


METHODS
We studied 16 patients with advanced PD with [(11)C]raclopride (RAC) PET. Each patient had RAC PET twice: once when medication had been withdrawn and once after an LD challenge. On the day of the LD challenge scan, oral 250 mg LD/25 mg carbidopa was given before scanning. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were rated in an "off" state before LD and again at the end of PET.


RESULTS
All the patients were still in "on" state at the end of their LD challenge RAC PET scans. Following LD, mean caudate and putamen RAC binding potentials (BPs) were significantly lower vs baseline, consistent with increased synaptic DA. Individual LD-induced improvements in UPDRS score correlated significantly with reductions in putaminal BP. Additionally, large putaminal RAC BP changes were associated with higher dyskinesia scores. When motor UPDRS subitems were examined, improvements in rigidity and bradykinesia, but not in tremor or axial symptoms, correlated with putamen DA release.


CONCLUSIONS
In advanced Parkinson disease, the improvement of rigidity and bradykinesia and the presence of dyskinesias after a single dose of oral levodopa are governed by the level of dopamine generated at striatal D2 receptors. In contrast, relief of parkinsonian tremor and axial symptoms is not related to striatal synaptic dopamine levels and presumably occurs via extrastriatal mechanisms.
Pavese
N
N
MRC Clinical Sciences Centre and Division of Neurosciences, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK.
Evans
A H
AH
Tai
Y F
YF
Hotton
G
G
Brooks
D J
DJ
Lees
A J
AJ
Piccini
P
P
D000284:Administration, Oral; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D004185:Disability Evaluation; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage; D018492:Dopamine Antagonists; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D002250:Carbon Radioisotopes; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D020891:Raclopride; D007980:Levodopa; D004298:Dopamine