Extrastriatal dopamine D2 and D3 receptors in early and advanced Parkinson's disease.
OBJECTIVE
To investigate whether dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the caudate-putamen are affected in PD.


BACKGROUND
Alterations in striatal D2-like dopamine receptors in PD have been extensively demonstrated using PET, but there are no studies focusing on extrastriatal D2/3Rs.


METHODS
Fourteen unmedicated patients with idiopathic early PD with predominantly left-sided symptoms, 14 levodopa-medicated patients with advanced PD, and 20 normal age-matched controls were examined using PET. PET scanning was performed with a novel high-affinity D2/3R radioligand ([11C]FLB 457) and a PET scanner in three-dimensional mode.


RESULTS
In advanced PD, the binding potential of [11C]FLB 457 in the dorsolateral prefrontal cortex was decreased by 40% (p < 0.01), in the anterior cingulate cortex by 20% (p < 0.01), and in the medial thalamus by 17% (p < 0.05) compared with healthy controls. In early PD, the extrastriatal [11C]FLB 457 binding potentials were not significantly different compared with the control group. However, the binding potential in the anterior cingulate cortex (29%; p < 0. 05) was higher in early PD compared with advanced PD.


CONCLUSIONS
These results imply that the D2/3 receptor subtypes outside the striatum are affected in advanced PD but not in the early stages of the disease, and that this receptor decline is present in the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus.
Kaasinen
V
V
Department of Neurology, University of Turku, Finland. valtteri.kaasinen@pet.tyks.fi
Någren
K
K
Hietala
J
J
Oikonen
V
V
Vilkman
H
H
Farde
L
L
Halldin
C
C
Rinne
J O
JO
D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D015259:Dopamine Agents / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000493:pharmacokinetics; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; C493593:DRD3 protein, human; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C065065:FLB 457; D007980:Levodopa