Document Detail


In vivo and in vitro validation of reference tissue models for the mGluR(5) ligand [(11)C]ABP688.
MedLine Citation:
PMID:  20531460     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
David Elmenhorst; Luciano Minuzzi; Antonio Aliaga; Jared Rowley; Gassan Massarweh; Mirko Diksic; Andreas Bauer; Pedro Rosa-Neto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-09
Journal Detail:
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:
Created Date:  2010-08-03     Completed Date:  2010-09-07     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1538-49     Citation Subset:  IM    
Affiliation:
Institute of Neurosciences and Medicine, INM-2, Research Center Juelich, Juelich, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Blockade of astrocytic glutamate uptake in rats induces signs of anhedonia and impaired spatial memo...
Next Document:  Cell number and timing of transplantation determine survival of human neural stem cell grafts in str...