Quantification of 5-HT2A receptors in the human brain using [18F]altanserin-PET and the bolus/infusion approach

The aim of the present study is to describe and validate a method for accurate quantification of 5-hydroxytryptamine (5-HT)(2A) receptors using [F-18]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 It. Steady state was attained in brain and plasma within 2 h, and time-activity curves remained constant for another 3 It. To represent free and nonspecifically bound [18 F]altanserin and its radiolabeled metabolites only, cerebellum must show no displacement in 5-HT,, displacement studies. To validate this, saturating doses of cold ketanserin were administered and it was found that specific binding of [F-18]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 mid-scan time started 2 h after [F-18]altanserin administration. The mean percentage rate of change per hour in the outcome parameter, DV3', was low (mean -0.3% h(-1); range -7.3-7.2% h(-1)) and no correlation of DV3' versus time was demonstrated. It is concluded that 5-HT2A receptor studies can be conducted within 2 h of [F-18]altanserin infusion, yielding reliable results.