Journal Article PreJuSER-22269

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Test-Retest Stability of Cerebral mGluR5 Quantification Using [11C]ABP688 and Positron Emission Tomography in Rats

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2012
Wiley-Liss New York, NY

Synapse 66, 552 - 560 () [10.1002/syn.21542]

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Abstract: This study evaluates the reproducibility of the quantification of metabotropic glutamate receptor type 5 (mGluR₅) densities in rats using the PET radiotracer [¹¹C]ABP688 and pharmacokinetic models that are based on an input function, which is derived from a reference tissue. Seven rats underwent dynamic PET scans (60 min) after bolus injection of [¹¹C]ABP688. Kinetic analyses included: binding potential (BP(ND) ) determined by calculating (a) the simplified reference tissue model (SRTM) and (b) its two-steps simplified version (SRTM2); (c) multilinear reference tissue model (MRTM) and (d) its 2-parameter version (MRTM2); (e) noninvasive graphical analysis (NIGA). Parametric images were generated representing BP(ND) by the MRTM2 model. BP(ND) determinations were reproducible with low to acceptable variability ranging from 5 to 10% and reproducibility scores (intraclass correlation coefficient) between 0.51 and 0.88. The pharmacokinetic model that showed lowest overall variability was the SRTM. In contrast, the use of the NIGA was associated with significantly lower reproducibility scores. Comparison of parametric images revealed no significant bias between test and retest measurements and is therefore suitable to compare groups at voxel levels. In conclusion, our results suggest that noninvasive quantification of [¹¹C]ABP688 imaging is reproducible and reliable for PET studies of the cerebral mGluR₅ in rats.

Keyword(s): Algorithms (MeSH) ; Animals (MeSH) ; Brain: radionuclide imaging (MeSH) ; Brain Chemistry (MeSH) ; Carbon Radioisotopes: chemistry (MeSH) ; Image Interpretation, Computer-Assisted (MeSH) ; Kinetics (MeSH) ; Male (MeSH) ; Oximes: analysis (MeSH) ; Oximes: chemistry (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Pyridines: analysis (MeSH) ; Pyridines: chemistry (MeSH) ; Rats (MeSH) ; Rats, Sprague-Dawley (MeSH) ; Receptors, Metabotropic Glutamate: analysis (MeSH) ; Reproducibility of Results (MeSH) ; 3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime ; Carbon Radioisotopes ; Oximes ; Pyridines ; Receptors, Metabotropic Glutamate ; metabotropic glutamate receptor 5 ; J ; positron emission tomography (auto) ; test-retest (auto) ; kinetic modeling (auto) ; [11C]ABP688 (auto)

Classification:

Note: Contract grant sponsor: Heinrich Hertz Foundation of the Ministry of Science and Technology; Contract grant sponsor: North-Rhine Westfalia, Germany; Contract grant sponsor: Alzheimer's Association new investigator award; Contract grant number: NIRG-08-92090; Contract grant sponsor: Fonds de la Recherche en Sante du Quebec (FRSQ); Contract grant sponsor: Chercheur Burcier award (PRN); Contract grant sponsor: Aisenstadt Foundation.

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 2012
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Medline ; BIOSIS Previews ; Current Contents - Life Sciences ; JCR ; NCBI Molecular Biology Database ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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