Quantification of 11C-SB207145-PET for 5-HT4 receptors in the human brain: Preliminary results

Abstract

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Objectives: 5-HT4 receptors are of pharmacological interest in Alzheimer’s Disease because of their involvement in learning and memory. The purpose of the study is to evaluate a novel 5-HT4-receptor tracer, [11C]-SB207145, for positron emission tomography (PET). Methods: Three healthy subjects (2 females and 1 male) have been included so far in the study. Magnetic resonance imaging (MRI) was performed as well as a 2-hour PET scan after a bolus injection of [11C]-SB207145. Arterial blood samples were drawn regularly during the scan for measurements of radioactivity. At least 5 samples were further processed by high-pressure liquid chromatography to measure the fraction of plasma activity representing unmetabolized parent compound. From these measures a metabolite corrected arterial input function to the brain was established. Volumes of interest (VOI’s) were delineated automatically on coregistered MRI images, and partial volume corrected mean VOI values were extracted from the different time points in the PET images to establish the tissue activity curves of each VOI. Results: The basal ganglia showed the highest binding followed by the hippocampus and the cortices in accordance with earlier findings (1). In the low binding regions the two-tissue-compartment (2-TC) model was necessary to describe the tissue activity data. In the high binding regions the 2-TC model only showed a marginally better description of the data compared to the one-tissue compartment model. Using cerebellum as a reference region, the simplified reference tissue model (SRTM) showed a 30% underestimation of the BP2 compared to the 2-TC model. This is most likely due to the slow tissue kinetics of the tracer. Conclusions: The underestimation of BP2 using the SRTM is consistent with earlier findings in pigs (2). Further studies are ongoing to determine the appropriate kinetic modeling approach. 1. Wishart, M. et al. (2003). J Cereb Blood Flow Metab (Proc. of Brain’03) 2. Comley R. et al. (2006). NeuroImage 31 (Abstract for NRM06)