Abstract
Background[11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([11C]DASB) is currently the mostly used radiotracer for positron emission tomography (PET) quantitative studies of the serotonin transporter (SERT) in the human brain but has never been validated in dogs. The first objective was therefore to evaluate normal [11C]DASB distribution in different brain regions of healthy dogs using PET. The second objective was to provide less invasive and more convenient alternative methods to the arterial sampling-based kinetic analysis.ResultsA dynamic acquisition of the brain was performed during 90 min. The PET images were coregistered with the magnetic resonance images taken prior to the study in order to manually drawn 20 regions of interest (ROIs). The highest radioactivity concentration of [11C]DASB was observed in the hypothalamus, raphe nuclei and thalamus and lowest levels in the parietal cortex, occipital cortex and cerebellum.The regional radioactivity in those 20 ROIs was quantified using the multilinear reference tissue model 2 (MRTM2) and a semi-quantitative method. The values showed least variability between 40 and 60 min and this time interval was set as the optimal time interval for [11C]DASB quantification in the canine brain. The correlation (R2) between the MRTM2 and the semi-quantitative method using the data between 40 and 60 min was 99.3 % (two-tailed p-value < 0.01).ConclusionsThe reference tissue models and semi-quantitative method provide a more convenient alternative to invasive arterial sampling models in the evaluation of the SERT of the normal canine brain. The optimal time interval for static scanning is set at 40 to 60 min after tracer injection.
Highlights
In vivo imaging of the living brain can be performed with positron emission tomography (PET), based on the detection of two opposite 511 keV gamma-rays that result from the annihilation of a positron and a negatron
The highest radioactivity concentration of [11C]DASB was observed in the hypothalamus, raphe nuclei and thalamus, intermediate levels were observed in the basal ganglia, hippocampus and frontal cortex, modest levels in the anterior and posterior cingulate gyri and temporal cortex, and low levels in the parietal cortex, occipital cortex and cerebellum
The highest radioactivity levels were observed in the hypothalamus, raphe nuclei and thalamus, intermediate levels were observed in the basal ganglia, hippocampus and frontal cortex, modest levels in the anterior and posterior cingulate gyri and temporal cortex, and low levels in the parietal cortex, occipital cortex and cerebellum
Summary
In vivo imaging of the living brain can be performed with positron emission tomography (PET), based on the detection of two opposite 511 keV gamma-rays that result from the annihilation of a positron and a negatron. Involvement of the serotonergic system in impulsive aggression, anxiety and compulsive disorders was demonstrated with single photon emission computed tomography [4,5,6]. As the primary molecular target of the selective serotonin reuptake inhibitors (SSRIs), the most common antidepressant drugs used in human medicine, the serotonin transporter (SERT) has been the focus of many studies in the past years. It is located on the presynaptic nerve endings of serotonergic neurons.
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