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Quantitative positron emission tomography of mG luR5 in rat brain with [ 18 F]PSS232 at minimal invasiveness and reduced model complexity
Author(s) -
Müller Herde Adrienne,
Keller Claudia,
Milicevic Sephton Selena,
Mu Linjing,
Schibli Roger,
Ametamey Simon M.,
Krämer Stefanie D.
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13001
Subject(s) - positron emission tomography , radioligand , metabotropic glutamate receptor 5 , binding potential , nuclear medicine , chemistry , biomedical engineering , metabotropic glutamate receptor , glutamate receptor , receptor , medicine , biochemistry
Imaging the density of metabotropic glutamate receptor 5 ( mG luR5) in brain by positron emission tomography ( PET ) is of interest in relation to several brain disorders. We have recently introduced [ 18 F] PSS 232, an F‐18‐labeled analog of the mG luR5‐targeting [ 11 C] ABP 688. 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 mG luR5 quantitative PET with [ 18 F] PSS 232. We further aimed at defining models of low complexity for quantitative PET with [ 18 F] PSS 232. 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] ABP 688 at lower unspecific accumulation of unchanged [ 18 F] PSS 232, 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] PSS 232 is a promising radioligand for mG luR5 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.