Quantitative positron emission tomography of mGluR5 in rat brain with [18F]PSS232 at minimal invasiveness and reduced model complexity.

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 [¹⁸F] PSS232, an F-18-labeled analog of the mGluR5-targeting [¹¹C] 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 [¹⁸F] PSS232. We further aimed at defining models of low complexity for quantitative PET with [¹⁸F] 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 [¹¹C] ABP688 at lower unspecific accumulation of unchanged [¹⁸F] 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. [¹⁸F] PSS232 is a promising radioligand for mGluR5 quantification. [ABSTRACT FROM AUTHOR]