The aim of the present study is to describe and validate a method for accurate 
quantification of 5-hydroxytryptamine (5-HT)(2A) receptors using 
[18F]altanserin-positron emission tomography (PET) and the bolus/infusion 
approach. A bolus/infusion ratio of 1.75 h aimed at attaining rapid steady state 
in blood and brain was predicted from previous bolus studies performed in our 
laboratory. The infusion schedule was tested in normal subjects (n = 10) using 
dynamic PET and frequent plasma sampling for 6 h. Steady state was attained in 
brain and plasma within 2 h, and time-activity curves remained constant for 
another 3 h. To represent free and nonspecifically bound [18F]altanserin and its 
radiolabeled metabolites only, cerebellum must show no displacement in 5-HT(2A) 
displacement studies. To validate this, saturating doses of cold ketanserin were 
administered and it was found that specific binding of [18F]altanserin decreased 
uniformly to the level of the cerebellum and no change in the cerebellar 
time-activity curve was found after ketanserin administration. A shorter 
experimental setup was tested in a second group (n = 20) including patients with 
neuropsychiatric disorders. Dynamic PET (five frames of 8 minutes each) and 
venous blood sampling at midscan time started 2 h after [18F]altanserin 
administration. The mean percentage rate of change per hour in the outcome 
parameter, DV(3)', was low (mean -0.3% h-1; range -7.3-7.2% h-1) and no 
correlation of DV(3)' versus time was demonstrated. It is concluded that 
5-HT(2A) receptor studies can be conducted within 2 h of [18F]altanserin 
infusion, yielding reliable results.