Abstract

This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs.

Highlights

  • The serotonin transporter (SERT) is a plasma membrane transporter that belongs to the neurotransmitter sodium symporter (NSS) family

  • The aim of this study is to present an evaluation of the [11C]DASB positron emission tomography (PET) data obtained in beagles, where different standard kinetic models for quantification were assessed using a metabolite corrected arterial plasma input function

  • During the first minutes after tracer injection, the fraction of unmetabolized [11C]DASB in arterial plasma rapidly declined to 53 ± 3% at 5 minutes

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Summary

Objectives

The aim of this study is to present an evaluation of the [11C]DASB PET data obtained in beagles, where different standard kinetic models for quantification were assessed using a metabolite corrected arterial plasma input function

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