The feasibility of in vivo serotonin 5HT(2) receptor binding measurement using 
[18F]altanserin as a radioligand has been well established. In this study, the 
postsynaptic receptor binding potential of this ligand was examined as a 
possible indicator of synaptic serotonin content after pharmacological 
challenge. Studies were performed in 11 subjects with a history of recurrent 
major depression. Six of them received serotonergic antidepressive treatment at 
the time of the experiment, the other five patients were untreated. Two PET 
measurements were carried out in each subject within 2 or 3 days. Before one of 
the measurements, 25 mg of the serotonin re-uptake inhibitor clomipramine were 
given intravenously, the other measurement was done without pharmacological 
challenge. The data were analyzed using non-linear least-square regression and 
Logan's graphical method. In the whole group of subjects, binding potential and 
distribution volume of altanserin decreased following clomipramine challenge. 
The decrease was between 14 (P=0.03) and 23% (P=0.004). This effect was mainly 
seen in subjects not on antidepressive medication. Clomipramine challenge 
probably increased the synaptic serotonin level, which competed with altanserin 
leading to the lowered binding potential. The paradigm might, thus, be useful to 
estimate serotonin release in vivo. Pretreatment with serotonergic 
antidepressants reduces the effect of clomipramine.