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- W2079119077 abstract "Two selective radioligands of gamma aminobutyric acid (GABA)A receptors containing the alpha5 subunit, [3H]L655,708 and [3H]RY80, were evaluated in rats as potential in vivo tracers for positron emission tomography (PET). Brain uptake index (BUI), a measure of first pass extraction, was moderate for [3H]L655,708 (BUI of 59%) and good for [3H]RY80 (BUI of 96%). This finding was consistent with their in vitro binding to plasma proteins of approximately 76% and 50%, respectively. Following intravenous injection of either radioligand, radioactivity in plasma was measured and uptake characteristics were assessed in brain within a time period relevant to PET scanning (up to 90 min). Discrete brain regions, such as frontal cortex, striatum, hypothalamus, thalamus, hippocampus, colliculi, medulla, and cerebellum, were sampled and the temporal distribution of radioactivity analysed. Despite the reasonable delivery to the brain, neither of the radioligands had sufficient retention in the tissues rich in alpha5-containing GABA(A) receptors to achieve a good selective signal. For both radioligands, a maximal tissue:cerebellum ratio of 1.5 was seen in hippocampus at 10 min after injection. Thus, neither of the compounds studied shows potential for further development as an in vivo PET ligand." @default.
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- W2079119077 date "1999-10-01" @default.
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- W2079119077 title "Evaluation of [methyl-3H]L655,708 and [ethyl-3H]RY80 as putative PET ligands for central GABAA receptors containing α5 subunit" @default.
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- W2079119077 doi "https://doi.org/10.1016/s0969-8051(99)00053-0" @default.
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