Reproducibility of Non-Invasive A1 Adenosine Receptor Quantification in the Rat Brain Using [18F]CPFPX and Positron Emission Tomography
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The A1AR antagonist 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([18F]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 [18F]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 [18F]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 [18F]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 [18F]CPFPX PET and allows longitudinal designs of in vivo imaging studies in rodents.
Key wordsA1 adenosine receptor [18F]CPFPX Positron emission tomography Test-retest Pharmacokinetic modeling Rat brain
Magdalene Vögeling, Dina Alghzawi, Tanja Juraschek, Larissa Damm, and Michaela Bohlen are gratefully acknowledged for excellent technical assistance, and Andreas Matusch for proofreading the manuscript. We thank Nikola Kornadt-Beck for the fruitful discussions and valuable support. Johannes Ermert and Heinz H. Coenen are gratefully acknowledged for the supply of the radioligand.
Conflict of Interest
The authors have no conflicts of interest to disclose.