Selective alterations of brain dopamine D(2) receptor binding in cirrhotic patients: results of a (11)C-N-methylspiperone PET study.
Alterations of the brain dopamine system have been implicated in the neurological complications of chronic liver failure. The present study was aimed at the measurement of dopamine D(2) binding sites in cirrhotic patients by positron emission tomography (PET) using (11)C-N-methylspiperone as ligand. The regions of interest (ROI) were designated on a three-dimensional stereotaxic ROI template (3DSRT). The pixel values of twelve ROIs corrected by the pixel value of the cerebellum after 80 min static scanning were used to quantitate changes in binding. D(2) binding sites were significantly decreased in the hippocampus and thalamus of cirrhotic patients and were positively correlated with serum bilirubin levels and Child-Pugh scores and were negatively correlated with prothrombin times (thalamus). Loss of D(2) sites was greater in thalamus and hippocampus of alcoholic cirrhotics compared to non-alcoholics. Statistically significant correlations were also observed between D(2) binding sites in hippocampus, thalamus and lenticular nuclei and history of overt encephalopathy. These findings suggest that D(2) receptor binding in some regions of brain in cirrhotic patients is influenced by factors such as the severity of liver damage and history of alcohol dependency or overt encephalopathy. Alterations of D(2) receptor sites indicative of dopaminergic synaptic dysfunction could play an important role in the pathogenesis of the cognitive and motor disturbances associated with chronic liver failure.
Watanabe
Yuki
Y
First Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan. yuwatana@iwate-med.ac.jp
Kato
Akinobu
A
Sawara
Kei
K
Butterworth
Roger F
RF
Sasaki
Toshiaki
T
Terasaki
Kazunori
K
Sera
Koichiro
K
Suzuki
Kazuyuki
K
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry / Q000502:physiology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008103:Liver Cirrhosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D013134:Spiperone; C039167:3-N-methylspiperone