Date Published: June 11, 2019
Publisher: Public Library of Science
Author(s): Glenn Pauwelyn, Lise Vlerick, Robrecht Dockx, Jeroen Verhoeven, Andre Dobbeleir, Kathelijne Peremans, Ingeborg Goethals, Tim Bosmans, Christian Vanhove, Filip De Vos, Ingeborgh Polis, Juri G. Gelovani.
Numerous studies have shown that the serotonin1A (5-HT1A) receptor is implicated in the pathophysiology and treatment of several psychiatric and neurological disorders. Furthermore, functional imaging studies in a variety of species have demonstrated that 4-(2´-Methoxyphenyl)-1-[2´-(N-2´´-pyridinyl)-p- [18F]fluorobenzamidoethylpiperazine ([18F]MPPF) is a valid and useful PET tracer to visualize the 5HT1A receptor. However, to our knowledge, [18F]MPPF has never been demonstrated in the canine brain. The ability to image the 5HT1A receptor with PET in dogs could improve diagnosis and therapy in both canine and human behavioural and neuropsychiatric disorders. To examine the potential use of [18F]MPPF in dogs, five healthy adult laboratory beagles underwent a 60-minutes dynamic PET scan with [18F]MPPF while arterial blood samples were taken. For each region of interest, total distribution volume (VT) and corresponding binding potential (BPND) were calculated using the 1-tissue compartment model (1-TC), 2-Tissue compartment model (2-TC) and Logan plot. The preferred model was chosen based on the goodness-of-fit, calculated with the Akaike information criterium (AIC). Subsequently, the BPND values of the preferred compartment model were compared with the estimated BPND values using three reference tissue models (RTMs): the 2-step simplified reference tissue model (SRTM2), the 2-parameter multilinear reference tissue model (MRTM2) and the Logan reference tissue model. According to the lower AIC values of the 2-TC model compared to the 1-TC in all ROIs, the 2-TC model showed a better fit. Calculating BPND using reference tissue modelling demonstrated high correlation with the BPND obtained by metabolite corrected plasma input 2-TC. This first-in-dog study indicates the results of a bolus injection with [18F]MPPF in dogs are consistent with the observations presented in the literature for other animal species and humans. Furthermore, for future experiments, compartmental modelling using invasive blood sampling could be replaced by RTMs, using the cerebellum as reference region.
The serotonin1A (5-HT1A) receptor is a G-protein-coupled receptor and is believed to be one of the most important 5-HT receptor subtypes [1–3]. Two different 5-HT1A receptor populations can be found in the mammalian brain [4–8]. The first population is located in the raphe nucleus and has an auto-receptor function that inhibits serotonin release at the nerve terminals. The second population is highly abundant in cortico-limbic areas, were it acts as post-synaptic receptor [2,9].
To our knowledge, this is the first study that examines the use of [18F]MPPF as PET-tracer to image the 5HT1A receptor in the canine brain.
This study describes the first step in the visualisation and quantification of the 5HT1A receptor using a bolus injection of [18F]MPPF in dogs. The results are consistent with the observations presented in the literature for other animal species and humans. The kinetics of [18F]MPPF in the canine brain could be best described by a 2-TC model. Furthermore, for future experiments, compartmental modelling using invasive blood sampling could be replaced by RTMs, using the cerebellum as reference region. This could be of great value for future experiments analysing the function of the 5HT1A receptor, improving both diagnosis and therapy in canine and human behavioural and neuropsychiatric disorders.