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Quantification of 5-HT 2A Receptors in the Human Brain Using [ 18 F]Altanserin-PET and the Bolus/Infusion Approach

2003; SAGE Publishing; Volume: 23; Issue: 8 Linguagem: Inglês

10.1097/01.wcb.0000074092.59115.23

1559-7016

Lars H. Pinborg, Karen Husted Adams, Claus Svarer, Søren Holm, Steen Gregers Hasselbalch, Steven Haugbøl, Jacob Madsen, Gitte M. Knudsen,

Advanced MRI Techniques and Applications

The aim of the present study is to describe and validate a method for accurate quantification of 5-hydroxytryptamine (5-HT) 2A receptors using [ 18 F]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 [ 18 F]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 [ 18 F]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 [ 18 F]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 [ 18 F]altanserin infusion, yielding reliable results.