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Peripheral benzodiazepine receptors in the brain of cirrhosis patients with manifest hepatic encephalopathy

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

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 11C-PK11195 brain PET.

Methods

Eight cirrhotic patients with an acute episode of clinically manifest HE (mean arterial ammonia 81 μmol/l) and five healthy subjects (22 μmol/l) underwent dynamic 11C-PK11195 and 15O-H2O PET, co-registered with MR images. Brain regions (putamen, cerebellum, cortex and thalamus) were delineated on co-registered 15O-H2 15O and MR images and copied to the dynamic 15O-H2O and 11C-PK11195 images. Regional cerebral blood flow (CBF) (15O-H2O scan) and the volume of distribution of PK11195 (11C-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.

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Acknowledgement

This study was supported by grants from the Novo Nordic Foundation.

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Authors and Affiliations

  1. PET Centre, Aarhus University Hospital, 8000, Aarhus, Denmark

    Peter Iversen, Dorthe Aagaard Hansen, Dirk Bender, Ole Lajord Munk, Paul Cumming & Susanne Keiding

  2. Department of Medicine V (Hepatology), Aarhus University Hospital, Aarhus, Denmark

    Dorthe Aagaard Hansen & Susanne Keiding

  3. Centre of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Aarhus, Denmark

    Anders Rodell

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  1. Peter Iversen
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  2. Dorthe Aagaard Hansen
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  5. Ole Lajord Munk
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Correspondence to Susanne Keiding.

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Iversen, P., Hansen, D.A., Bender, D. et al. Peripheral benzodiazepine receptors in the brain of cirrhosis patients with manifest hepatic encephalopathy. Eur J Nucl Med Mol Imaging 33, 810–816 (2006). https://doi.org/10.1007/s00259-005-0052-8

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  • DOI: https://doi.org/10.1007/s00259-005-0052-8

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