title: Quantitative positron emission tomography of mGluR5 in rat brain with [(18) F]PSS232 at minimal invasiveness and reduced model complexity.
abstract: Imaging the density of metabotropic glutamate receptor 5 (mGluR5) in brain by positron emission tomography (PET) is of interest in relation to several brain disorders. We have recently introduced [(18) F]PSS232, an F-18-labeled analog of the mGluR5-targeting [(11) C]ABP688. Quantitative PET requires kinetic modeling with an input function (IF) or an appropriate reference tissue model. We aimed at minimizing invasiveness of IF recording in rat and employing this protocol for mGluR5 quantitative PET with [(18) F]PSS232. We further aimed at defining models of low complexity for quantitative PET with [(18) F]PSS232. The IF was recorded in an arterio-venous shunt applied by minimally invasive cannulation. PET data were analyzed with a modified two-tissue compartment model including a single variable for radiometabolite correction in brain. We further evaluated a simple reference tissue model. Receptor-dependent accumulation was similar to [(11) C]ABP688 at lower unspecific accumulation of unchanged [(18) F]PSS232, in agreement with its higher plasma protein binding and lower lipophilicity. The minimally invasive protocol revealed similar results as the invasive shunt method and parameters calculated with the modified two-tissue compartment model were similar to those calculated with the standard model. The simple area under the curve ratios agreed with the Logan reference method. [(18) F]PSS232 is a promising radioligand for mGluR5 quantification. Methods were evaluated to quantify mGluR5 in rat brain by PET with [(18) F]PSS232. We present a minimally invasive protocol for input function recording. A two-tissue compartment model correcting for radiometabolites at reduced complexity is compared with the standard model. Finally, we demonstrate and explain why for [(18) F]PSS232 the area-under-the-curve ratio is a valid alternative to the Logan reference tissue analysis.
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences (D-CHAB), ETH Zurich, Zurich, Switzerland.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Müller Herde
authors.forename: Claudia
authors.initials: C
authors.lastname: Keller
authors.forename: Selena
authors.initials: S
authors.lastname: Milicevic Sephton
authors.forename: Linjing
authors.initials: L
authors.lastname: Mu
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Krämer
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D019788:Fluorodeoxyglucose F18 / Q000032:analysis* / Q000378:metabolism; D055786:Gene Knockout Techniques / Q000379:methods; D006801:Humans; D008297:Male; D023421:Models, Animal; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5 / Q000032:analysis* / Q000378:metabolism
chemical_list: C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D019788:Fluorodeoxyglucose F18
keywords: area under the curve; cannulation; mGluR5; quantitative PET; radiometabolite; receptor imaging