Journal Article

PreJuSER-10453

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png In vivo and in vitro validation of reference tissue models for the mGluR5 ligand (11C)ABP688

Elmenhorst, D.FZJ* ; Minuzzi, L. ; Aliaga, A. ; Rowley, J. ; Massarweh, G. ; Diksic, M. ; Bauer, A.FZJ* ; Rosa-Neto, P.

2010
Ovid [s.l.]

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Please use a persistent id in citations: doi:10.1038/jcbfm.2010.65

Abstract: 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.

Keyword(s): Animals (MeSH) ; Autoradiography: methods (MeSH) ; Binding Sites (MeSH) ; Brain: metabolism (MeSH) ; Brain: radionuclide imaging (MeSH) ; Carbon Radioisotopes: analysis (MeSH) ; Carbon Radioisotopes: metabolism (MeSH) ; Carbon Radioisotopes: pharmacokinetics (MeSH) ; Kinetics (MeSH) ; Male (MeSH) ; Oximes: analysis (MeSH) ; Oximes: metabolism (MeSH) ; Oximes: pharmacokinetics (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Pyridines: analysis (MeSH) ; Pyridines: metabolism (MeSH) ; Pyridines: pharmacokinetics (MeSH) ; Rats (MeSH) ; Rats, Sprague-Dawley (MeSH) ; Receptors, Metabotropic Glutamate: analysis (MeSH) ; Receptors, Metabotropic Glutamate: metabolism (MeSH) ; 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime ; Carbon Radioisotopes ; Oximes ; Pyridines ; Receptors, Metabotropic Glutamate ; metabotropic glutamate receptor 5 ; J ; autoradiography (auto) ; blocking (auto) ; kinetic modeling (auto) ; positron emission tomography (auto) ; [C-11]ABP688 (auto)

Note: This study was supported by the Alzheimer's Association new investigator grant, the Heinrich Hertz Foundation of the Ministry of Science and Technology, North-Rhine Westfalia, Germany (DE), Fonds de la Recherche en Sante du Quebec (FRSQ), Chercheur Burcier Award, Nussia and Andre Aisenstadt Foundation and Fondation Savoy.

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Contributing Institute(s):

1. Molekulare Organisation des Gehirns (INM-2)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (FUEK409) (FUEK409)
2. 89574 - Theory, modelling and simulation (POF2-89574) (POF2-89574)

Appears in the scientific report 2010

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