| Cerebral benzodiazepine receptor binding in vivo in patients with recurrent hepatic encephalopathy. | |
| | |
MedLine Citation:
|
PMID: 9252134 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Increased activation of the central benzodiazepine receptor (BZR) appears to play an important role in hepatic encephalopathy (HE). However, there is controversy regarding whether the density or affinity of BZRs is altered. A previous positron emission tomography (PET) study using the BZR antagonist [11C]flumazenil (FMZ) found two- to threefold greater cerebral cortical tracer uptake in recurrent HE, but did not account for impaired FMZ metabolism due to liver disease or assess the relative contributions of tracer delivery versus BZR binding. We hypothesized that correcting for these factors would affect estimations of BZR binding in HE. Nine patients with recurrent HE and 13 age-comparable controls were studied with [11C]FMZ PET. After intravenous administration of [11C]FMZ, arterial blood samples were collected, and PET images were acquired over 60 minutes. FMZ transport and binding maps were calculated for each subject by using a physiological tracer kinetic model. In agreement with the previous report, we found that FMZ reached a much higher level and was retained longer in the HE cerebral cortex despite similar total blood radioactivity levels in the two groups. However, the patients showed impaired hepatic metabolism of FMZ. After physiological modeling incorporating these data, significant increases in BZR binding were found in the thalamus (13%), cerebellum (20%), and pons (23%). There were minor, statistically insignificant increases in cerebral cortical (10%), putamen (12%), and whole brain (12%) BZR binding in patients with recurrent HE. These findings are in general agreement with results of autopsy studies, confirming a lack of major increases in cortical or basal ganglial BZR binding in HE. They emphasize that physiological tracer modeling should be used and altered peripheral radioligand metabolism considered in future PET studies of HE. |
| | |
Authors:
|
G A Macdonald; K A Frey; B W Agranoff; S Minoshima; R A Koeppe; D E Kuhl; B L Shulkin; M R Lucey |
Related Documents
:
|
1359574 - Benzodiazepine receptor binding of benzodiazepine hypnotics: receptor and ligand specif... 9378234 - Peripheral-type benzodiazepine receptors. 2166014 - The radiosynthesis of [18f]pk 14105 as an alternative radioligand for peripheral type b... 3262414 - Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for di... 6365664 - Characterization of the serum from a patient with insulin resistance and hypoglycemia. ... 12525164 - In vitro characterization of lactoferrin aggregation and amyloid formation. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Hepatology (Baltimore, Md.) Volume: 26 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 1997 Aug |
Date Detail:
|
Created Date: 1997-08-28 Completed Date: 1997-08-28 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 8302946 Medline TA: Hepatology Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 277-82 Citation Subset: IM |
Affiliation:
|
Department of Internal Medicine, University of Michigan, Ann Arbor, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Brain / metabolism* Carbon Radioisotopes / diagnostic use Female Flumazenil / metabolism* Hepatic Encephalopathy / metabolism* Humans Male Middle Aged Receptors, GABA-A / analysis* Recurrence Tomography, Emission-Computed |
| Grant Support | |
ID/Acronym/Agency:
|
P50 NS15655/NS/NINDS NIH HHS; R01 MH49748/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Carbon Radioisotopes; 0/Receptors, GABA-A; 78755-81-4/Flumazenil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Elevated glomerular and blood mononuclear lymphocyte nitric oxide production in rats with chronic bi...
Next Document: Factors regulating tumor pressure in hepatocellular carcinoma and implications for tumor spread.