Effects of Citalopram Infusion on the Serotonin Transporter Binding of [¹¹C]DASB in Healthy Controls

Abstract

The positron emission tomography (PET) ligand [ 11 C]DASB is currently the most widely used imaging agent for quantitative studies of the serotonin transporter (SERT) in human brain. The aim of this work was to assess the effects of an intravenous infusion of 10 mg citalopram, a selective serotonin reuptake inhibitor (SSRI), before the PET scan on the kinetics of [ 11 C]DASB in arterial plasma and in selected brain regions. Four healthy male volunteers underwent two PET scans with a mean of 523 MBq injected activity after either placebo or citalopram infusion in a randomised design. The citalopram infusion led to a substantial increase of the area under the curve of the metabolitecorrected arterial plasma input function. Total volumes of distribution V T were estimated applying the Logan plot to regional time-activity curves or by generating parametric maps with spectral analysis. A mean reduction of the cerebellar V T of 19% with Logan analysis and of 24% with spectral analysis was observed after citalopram infusion, which confirms previous findings of displaceable SERT ligand binding in cerebellar grey matter. The SERT occupancy for six target regions with moderate to high binding was 60% derived from BP ND and 69% derived from BP P .

Tracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter

“…This pattern was similar to that of [ 11 C]DASB. 35 The plasma free fraction (f P ) of [ 11 C]AFM was 8.6 ± 1.8% (n ¼ 10), which was similar to that in baboons (9.6 ± 0.5%, n ¼ 4).…”

“…The initial metabolism rate of [ 11 C]AFM was faster or similar to that of [ 11 C]DASB. 28,35,37 The effect of interpolation/extrapolation of parent fraction curves was investigated: (1) Assuming very slow metabolism at early time, i.e., the first 3 minutes parent fraction was set to one. (2) Avoiding the potential extrapolation errors, the parent fraction at 90 to 120 minutes was set to be the (constant) 90-minute value.…”

“…However, several blocking studies showed that there were changes in radioligand binding in the cerebellum, especially in the white matter and vermis. 35,49 In this study, white matter, vermis, and cerebellar subregions with confirmed blocking effect by citalopram were excluded from the cerebellum region used in our analysis.…”

Quantification of Ligand PET Studies using a Reference Region with a Displaceable Fraction: Application to Occupancy Studies with [11C]-DASB as an Example

“…The amount of [ 11 C]-DASB and its radioactive metabolites at a given time point were calculated from the decay-corrected integrated radio-chromatogram and from the levels of radioactivity in the solid-phase extraction eluate and expressed as a percentage of total plasma sample injected. Detailed information on data extraction and processing is reported in the original reference (Hinz et al, 2008).…”

“…For the occupancy study, the data already published in Hinz et al (2008) were reanalyzed. In short, four healthy male volunteers (aged 37, 42, 49, and 57 years) were recruited and underwent two PET scans with […”