Peripheral benzodiazepine receptors in the brain of cirrhosis patients with manifest hepatic encephalopathy.
OBJECTIVE
It has been suggested that ammonia-induced enhancement of peripheral benzodiazepine receptors (PBRs) in the brain is involved in the development of hepatic encephalopathy (HE). This hypothesis is based on animal experiments and studies of post-mortem human brains using radiolabelled PK11195, a specific ligand for PBR, but to our knowledge has not been tested in living patients. The aim of the present study was to test this hypothesis by measuring the number of cerebral PBRs in specific brain regions in cirrhotic patients with an acute episode of clinically manifest HE and healthy subjects using dynamic (11)C-PK11195 brain PET.


METHODS
Eight cirrhotic patients with an acute episode of clinically manifest HE (mean arterial ammonia 81 micromol/l) and five healthy subjects (22 micromol/l) underwent dynamic (11)C-PK11195 and (15)O-H(2)O PET, co-registered with MR images. Brain regions (putamen, cerebellum, cortex and thalamus) were delineated on co-registered (15)O-H(2) (15)O and MR images and copied to the dynamic (15)O-H(2)O and (11)C-PK11195 images. Regional cerebral blood flow (CBF) ((15)O-H(2)O scan) and the volume of distribution of PK11195 ((11)C-PK11195 scan) were calculated by kinetic analysis.


RESULTS
There were regional differences in the CBF, with lowest values in the cortex and highest values in the putamen in both groups of subjects (p<0.05), but no significant differences between the groups. There were no significant differences in the volume of distribution of PK11195 (V (d)) between regions or between the two groups of subjects. Mean values of V (d) ranged from 1.0 to 1.1 in both groups of subjects.


CONCLUSIONS
The results do not confirm the hypothesis of an increased number of PBRs in patients with HE.
PET Centre, Aarhus University Hospital, 8000 Aarhus, Denmark.
Peter
P
Iversen
Dorthe Aagaard
DA
Hansen
Dirk
D
Bender
Anders
A
Rodell
Ole Lajord
OL
Munk
Paul
P
Cumming
Susanne
S
Keiding
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006501:Hepatic Encephalopathy / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008103:Liver Cirrhosis / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000378:metabolism*; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195