TY  - JOUR
AU  - Elmenhorst, D.
AU  - Minuzzi, L.
AU  - Aliaga, A.
AU  - Rowley, J.
AU  - Massarweh, G.
AU  - Diksic, M.
AU  - Bauer, A.
AU  - Rosa-Neto, P.
TI  - In vivo and in vitro validation of reference tissue models for the mGluR5 ligand (11C)ABP688
JO  - Journal of cerebral blood flow & metabolism
VL  - 30
SN  - 0271-678X
CY  - [s.l.]
PB  - Ovid
M1  - PreJuSER-10453
SP  - 1538 - 1549
PY  - 2010
N1  - 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.
AB  - 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.
KW  - Animals
KW  - Autoradiography: methods
KW  - Binding Sites
KW  - Brain: metabolism
KW  - Brain: radionuclide imaging
KW  - Carbon Radioisotopes: analysis
KW  - Carbon Radioisotopes: metabolism
KW  - Carbon Radioisotopes: pharmacokinetics
KW  - Kinetics
KW  - Male
KW  - Oximes: analysis
KW  - Oximes: metabolism
KW  - Oximes: pharmacokinetics
KW  - Positron-Emission Tomography: methods
KW  - Pyridines: analysis
KW  - Pyridines: metabolism
KW  - Pyridines: pharmacokinetics
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - Receptors, Metabotropic Glutamate: analysis
KW  - Receptors, Metabotropic Glutamate: metabolism
KW  - 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime (NLM Chemicals)
KW  - Carbon Radioisotopes (NLM Chemicals)
KW  - Oximes (NLM Chemicals)
KW  - Pyridines (NLM Chemicals)
KW  - Receptors, Metabotropic Glutamate (NLM Chemicals)
KW  - metabotropic glutamate receptor 5 (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:20531460
C2  - pmc:PMC2949244
UR  - <Go to ISI:>//WOS:000280561900013
DO  - DOI:10.1038/jcbfm.2010.65
UR  - https://juser.fz-juelich.de/record/10453
ER  -