TY  - JOUR
AU  - Boy, C.
AU  - Meyer, P. T.
AU  - Kircheis, G.
AU  - Holschbach, M. H.
AU  - Herzog, H.
AU  - Elmenhorst, D.
AU  - Kaiser, H. J.
AU  - Coenen, H. H.
AU  - Häussinger, D.
AU  - Zilles, K.
AU  - Bauer, A.
TI  - Cerebral A(1) adenosine receptors (A(1)AR) in liver cirrhosis
JO  - European Journal of Nuclear Medicine and Molecular Imaging
VL  - 35
SN  - 1619-7070
CY  - Heidelberg [u.a.]
PB  - Springer-Verl.
M1  - PreJuSER-61611
SP  - 589 - 597
PY  - 2008
N1  - Record converted from VDB: 12.11.2012
AB  - The cerebral mechanisms underlying hepatic encephalopathy (HE) are poorly understood. Adenosine, a neuromodulator that pre- and postsynaptically modulates neuronal excitability and release of classical neurotransmitters via A(1) adenosine receptors (A(1)AR), is likely to be involved. The present study investigates changes of cerebral A(1)AR binding in cirrhotic patients by means of positron emission tomography (PET) and [(18)F]CPFPX, a novel selective A(1)AR antagonist.PET was performed in cirrhotic patients (n = 10) and healthy volunteers (n = 10). Quantification of in vivo receptor density was done by Logan's non-invasive graphical analysis (pons as reference region). The outcome parameter was the apparent binding potential (aBP, proportional to B (max)/K (D)).Cortical and subcortical regions showed lower A(1)AR binding in cirrhotic patients than in controls. The aBP changes reached statistical significance vs healthy controls (p < 0.05, U test with Bonferroni-Holm adjustment for multiple comparisons) in cingulate cortex (-50.0%), precentral gyrus (-40.9%), postcentral gyrus (-38.6%), insular cortex (-38.6%), thalamus (-32.9%), parietal cortex (-31.7%), frontal cortex (-28.6), lateral temporal cortex (-28.2%), orbitofrontal cortex (-27.9%), occipital cortex (-24.6), putamen (-22.7%) and mesial temporal lobe (-22.4%).Regional cerebral adenosinergic neuromodulation is heterogeneously altered in cirrhotic patients. The decrease of cerebral A(1)AR binding may further aggravate neurotransmitter imbalance at the synaptic cleft in cirrhosis and hepatic encephalopathy. Different pathomechanisms may account for these alterations including decrease of A(1)AR density or affinity, as well as blockade of the A(1)AR by endogenous adenosine or exogenous xanthines.
KW  - Adult
KW  - Aged
KW  - Brain: metabolism
KW  - Brain: radionuclide imaging
KW  - Female
KW  - Humans
KW  - Liver Cirrhosis: metabolism
KW  - Liver Cirrhosis: radionuclide imaging
KW  - Male
KW  - Middle Aged
KW  - Radiopharmaceuticals: diagnostic use
KW  - Radiopharmaceuticals: pharmacokinetics
KW  - Receptor, Adenosine A1: metabolism
KW  - Tissue Distribution
KW  - Xanthines: diagnostic use
KW  - Xanthines: pharmacokinetics
KW  - 8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine (NLM Chemicals)
KW  - Radiopharmaceuticals (NLM Chemicals)
KW  - Receptor, Adenosine A1 (NLM Chemicals)
KW  - Xanthines (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:18000666
UR  - <Go to ISI:>//WOS:000254402800018
DO  - DOI:10.1007/s00259-007-0586-z
UR  - https://juser.fz-juelich.de/record/61611
ER  -