PURPOSE: 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. CONCLUSION: The results do not confirm the hypothesis of an increased number of PBRs in patients with HE.
PURPOSE: 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 cirrhoticpatients with an acute episode of clinically manifest HE and healthy subjects using dynamic (11)C-PK11195 brain PET. METHODS: Eight cirrhoticpatients 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. CONCLUSION: The results do not confirm the hypothesis of an increased number of PBRs in patients with HE.
Authors: J Versijpt; J C Debruyne; K J Van Laere; F De Vos; J Keppens; K Strijckmans; E Achten; G Slegers; R A Dierckx; J Korf; J L De Reuck Journal: Mult Scler Date: 2005-04 Impact factor: 6.312
Authors: G Le Fur; M L Perrier; N Vaucher; F Imbault; A Flamier; J Benavides; A Uzan; C Renault; M C Dubroeucq; C Guérémy Journal: Life Sci Date: 1983-04-18 Impact factor: 5.037
Authors: J Logan; J S Fowler; N D Volkow; A P Wolf; S L Dewey; D J Schlyer; R R MacGregor; R Hitzemann; B Bendriem; S J Gatley Journal: J Cereb Blood Flow Metab Date: 1990-09 Impact factor: 6.200
Authors: A Gerhard; B Neumaier; E Elitok; G Glatting; V Ries; R Tomczak; A C Ludolph; S N Reske Journal: Neuroreport Date: 2000-09-11 Impact factor: 1.837
Authors: M A Kropholler; R Boellaard; E H Elzinga; C J van der Laken; K Maruyama; R W Kloet; A E Voskuyl; B A C Dijkmans; A A Lammertsma Journal: Eur J Nucl Med Mol Imaging Date: 2008-11-29 Impact factor: 9.236