Abstract
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.
Highlights
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 [1,2,3]
Several positron emission tomography (PET)-studies have demonstrated that 4-(2 ́-Methoxyphenyl)-1-[2 ́-(N2 ́ ́-pyridinyl)-p- [18F]fluorobenzamidoethylpiperazine ([18F]MPPF) is a valid and reliable PET-tracer for imaging the 5HT1A receptor in the human brain [10,15]
This study describes the first step in the visualisation and quantification of the 5HT1A receptor using a bolus injection of [18F]MPPF in dogs
Summary
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 [1,2,3]. In vitro binding assays with the tritiated compound showed that this 5-HT1A antagonist has a high affinity (Kd: 0.34 nM) and good selectivity towards the 5-HT1A receptors [16] Other advantages of this radiotracer are a high initial brain uptake, the relatively simple radiochemical synthesis compared to other 5HT1A PET-tracers (for example: [11C]WAY100635) and the long physical half-life of 18F, which permits distribution from production facilities to remote hospitals [1,10,17]. Functional imaging studies of the 5-HT1A receptor in dogs could improve our understanding of several canine behavioral disorders and may serve as a tool to improve diagnosis and treatment of these disorders
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