Abstract
BackgroundCurrently, [18F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region.ResultsThe distribution of [18F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling.ConclusionsThis study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5-HT2A receptor in the canine brain.
Highlights
[18F] altanserin is the most frequently used Positron emission tomography (PET)-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs
In order to help calculating the sample size of future PET studies with [18F] altanserin, the assessment of the testretest variability can be performed in a future study. In conclusion this first-in-dog study describes a first step in the visualization and quantification of the 5HT2A receptor in the canine brain after bolus injection of [18F]altanserin
To avoid invasive blood sampling in future experiments, reference tissue models can be used instead of compartmental modelling, using the cerebellum as reference region
Summary
[18F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. The in vivo formation of lipophilic radiolabeled metabolites that cross the blood brain barrier complicates kinetic modeling with this radiotracer [15, 17, 20, 21] Correction for these radiolabeled metabolites can be achieved by the application of a bolus-infusion protocol with equilibrium imaging [23] or by using a dual-input functional approach [24] but is not feasible in clinical routine. On the contrary, increased binding potential of the 5-HT2A receptor was found in dogs suffering from impulsive aggression [31] These findings emphasize the role of the 5HT2A receptor in canine behavioral disorders. Using the advantages of PET imaging over other imaging techniques to study the 5-HT2A receptor in the dogs, its involvement in several behavioral disorders can be further investigated which could help to gain insight in the pathophysiology of certain canine behavioural disorders and would help to guide the treatment of these disorders
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