%0 Journal Article
%A Elmenhorst, D.
%A Minuzzi, L.
%A Aliaga, A.
%A Rowley, J.
%A Massarweh, G.
%A Diksic, M.
%A Bauer, A.
%A Rosa-Neto, P.
%T In vivo and in vitro validation of reference tissue models for the mGluR5 ligand (11C)ABP688
%J Journal of cerebral blood flow & metabolism
%V 30
%@ 0271-678X
%C [s.l.]
%I Ovid
%M PreJuSER-10453
%P 1538 - 1549
%D 2010
%Z 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.
%X 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.
%K Animals
%K Autoradiography: methods
%K Binding Sites
%K Brain: metabolism
%K Brain: radionuclide imaging
%K Carbon Radioisotopes: analysis
%K Carbon Radioisotopes: metabolism
%K Carbon Radioisotopes: pharmacokinetics
%K Kinetics
%K Male
%K Oximes: analysis
%K Oximes: metabolism
%K Oximes: pharmacokinetics
%K Positron-Emission Tomography: methods
%K Pyridines: analysis
%K Pyridines: metabolism
%K Pyridines: pharmacokinetics
%K Rats
%K Rats, Sprague-Dawley
%K Receptors, Metabotropic Glutamate: analysis
%K Receptors, Metabotropic Glutamate: metabolism
%K 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime (NLM Chemicals)
%K Carbon Radioisotopes (NLM Chemicals)
%K Oximes (NLM Chemicals)
%K Pyridines (NLM Chemicals)
%K Receptors, Metabotropic Glutamate (NLM Chemicals)
%K metabotropic glutamate receptor 5 (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:20531460
%2 pmc:PMC2949244
%U <Go to ISI:>//WOS:000280561900013
%R 10.1038/jcbfm.2010.65
%U https://juser.fz-juelich.de/record/10453