| In vivo and in vitro validation of reference tissue models for the mGluR(5) ligand [(11)C]ABP688. | |
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MedLine Citation:
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PMID: 20531460 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The primary objective of this study was to verify the suitability of reference tissue-based quantification methods of the metabotropic glutamate receptor type 5 (mGluR(5)) with [(11)C]ABP688. This study presents in vivo (Positron Emission Tomography (PET)) and in vitro (autoradiography) measurements of mGluR(5) densities in the same rats and evaluates both noninvasive and blood-dependent pharmacokinetic models for the quantification of [(11)C]ABP688 binding. Eleven rats underwent [(11)C]ABP688 PET scans. In five animals, baseline scans were compared with blockade experiments with the antagonist 1,2-methyl-6-(phenylethynyl)-pyridine (MPEP), and arterial blood samples were drawn and corrected for metabolites. Afterward, saturation-binding autoradiography was performed. Blocking with MPEP resulted in an average decrease of the total distribution volume (V(T)) between 43% and 58% (thalamus and caudate-putamen, respectively) but had no significant effect on cerebellar V(T) (mean reduction: -0.01%). Comparing binding potential (BP(ND)) based on the V(T) with noninvasively determined BP(ND) revealed an average negative bias of 0.7% in the caudate-putamen and an average positive bias of 3.1% in the low-binding regions. Scan duration of 50 minutes is required. The cerebellum is a suitable reference region for the quantification of mGluR(5) availability as measured with [(11)C]ABP688 PET in rats. Blood-based and reference region-based PET quantification shows a significant linear relationship to autoradiographic determinations. |
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Authors:
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David Elmenhorst; Luciano Minuzzi; Antonio Aliaga; Jared Rowley; Gassan Massarweh; Mirko Diksic; Andreas Bauer; Pedro Rosa-Neto |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-09 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 30 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-03 Completed Date: 2010-09-07 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1538-49 Citation Subset: IM |
Affiliation:
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Institute of Neurosciences and Medicine, INM-2, Research Center Juelich, Juelich, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoradiography / methods Binding Sites Brain / metabolism, radionuclide imaging* Carbon Radioisotopes / analysis, metabolism, pharmacokinetics Kinetics Male Oximes / analysis, metabolism*, pharmacokinetics* Positron-Emission Tomography / methods* Pyridines / analysis, metabolism*, pharmacokinetics* Rats Rats, Sprague-Dawley Receptors, Metabotropic Glutamate / analysis, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; 0/Carbon Radioisotopes; 0/Oximes; 0/Pyridines; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 5 |
| Comments/Corrections | |
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