Reproducibility of Non-Invasive A1 Adenosine Receptor Quantification in the Rat Brain Using [18F]CPFPX and Positron Emission Tomography

Abstract

The A1AR antagonist 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([(18)F]CPFPX) has recently been shown to be a suitable radiotracer for quantitative in vivo imaging of the A1 adenosine receptor (A1AR) in rats. The present study evaluates the reproducibility of non-invasive longitudinal A1AR studies with [(18)F]CPFPX and a dedicated small animal positron emission tomography (PET) scanner. Twelve male Sprague Dawley rats underwent four repeated dynamic PET scans with a bolus injection of [(18)F]CPFPX. A1AR availability was determined by different non-invasive approaches including simplified and multilinear reference tissue (olfactory bulb)-based models and graphical methods. The outcome parameter binding potential (BP) was evaluated in terms of variability and reproducibility. Repeated estimations of [(18)F]CPFPX BP ND gave reliable results with acceptable variability (mean 12%) and reproducibility (intraclass correlation coefficients raging from 0.57 to 0.68) in cortical and subcortical regions of the rat brain. With regard to kinetic models, test-retest stability of the simplified reference-tissue model (SRTM) was superior to multilinear and graphical approaches. Non-invasive quantification of A1AR density in the rat brain is reproducible and reliable with [(18)F]CPFPX PET and allows longitudinal designs of in vivo imaging studies in rodents.