Dopamine D1 receptor number--a sensitive PET marker for early brain degeneration in Huntington's disease.
D1-dopamine receptor binding in the brain was determined by positron emission tomography (PET) in five patients with Huntington's disease, in one asymptomatic gene carrier and in five control subjects. [11C] SCH 23390 was used as the radioligand. Brain morphology was recorded by MRI. The patients who all had a mild to moderate functional impairment showed an almost 50% reduction of putamen volume as well as D1-dopamine receptor density as compared to the controls. The total D1-dopamine receptor number in the putamen was reduced by 75% in the patient group. A similar reduction was found for the caudate nucleus. The asymptomatic gene carrier had volume and density values in the lower range of the control subjects. In the frontal neocortex there also tended to be a reduced D1-dopamine receptor binding in the symptomatic patients. The results indicate that [11C] SCH 23390 binding in combination with MRI can be used as a sensitive marker for early brain degeneration in Huntington's disease. This marker may be useful to monitor the pathophysiological effect of the disease gene and also to follow therapeutic interventions aiming at preventing the degenerative process.
Sedvall
G
G
Department of Clinical Neuroscience, Karolinska Hospital and Institute, Stockholm, Sweden.
Karlsson
P
P
Lundin
A
A
Anvret
M
M
Suhara
T
T
Halldin
C
C
Farde
L
L
D000328:Adult; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000503:physiopathology; D001552:Benzazepines / Q000493:pharmacokinetics; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000502:physiology*; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D012016:Reference Values; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D017447:Receptors, Dopamine D1