Quantification of 5-HT2A Receptors in the Human Brain Using [18F]Altanserin-PET and the Bolus/Infusion Approach

Abstract

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, 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-HT_2A receptor studies can be conducted within 2 h of [¹⁸F]altanserin infusion, yielding reliable results.