Extrastriatal dopamine D(2) receptor binding in Huntington's disease.
Huntington's disease (HD) is a neurodegenerative disorder, primarily affecting medium spiny neurones in the striatum. The density of striatal dopamine D(2) receptors is reduced in HD but there is little known about this biomarker in brain regions outside the striatum. The primary objective of this study was to compare extrastriatal dopamine D(2) receptor binding, in age-matched control subjects and patients with HD. All subjects were examined using a high-resolution positron emission tomography system and the high-affinity dopamine D(2) receptor radioligand [(11) C]FLB 457. A ROI based analysis was used with an atrophy correction method. Dopamine D(2) receptor binding potential was reduced in the striatum of patients with HD. Unlike the striatum, dopamine D(2) receptor binding in thalamic and cortical subregions was not significantly different from that in control subjects. A partial least square regression analysis which included binding potential values from all investigated cortical and subcortical regions revealed a significant model separating patients from controls, conclusively dependent on differences in striatal binding of the radioligand. Some clinical assessments correlated with striatal dopamine D(2) receptor binding, including severity of chorea and cognitive test performance. Hence, the present study demonstrates that dopamine D(2) receptors extrinsic to the striatum are well preserved in early to mid stage patients with HD. This observation may have implication for the development of therapy for HD.
Esmaeilzadeh
Mouna
M
PET Centre, Stockholm Brain Institute, Karolinska Institutet, Stockholm, Sweden. mouna.esmaeilzadeh@ki.se
Farde
Lars
L
Karlsson
Per
P
Varrone
Andrea
A
Halldin
Christer
C
Waters
Susanna
S
Tedroff
Joakim
J
D000328:Adult; D000368:Aged; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D013223:Statistics as Topic; D055815:Young Adult
D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457