PET quantification of 5-HT2A receptors in the human brain: A constant infusion paradigm with [F-18]altanserin

[F-18]altanserin has been used to label serotonin 5-HT2A receptors, which a re believed to be important in the pathophysiology of schizophrenia and dep ression. The purpose of this study was to test the feasibility of a constan t infusion paradigm for equilibrium modeling of [F-18]altanserin with PET. Kinetic modeling with [F-18]altanserin may be hampered by the presence of l ipophilic radiometabolites observed in plasma after intravenous administrat ion. Methods: Eight healthy volunteers were injected with [F-18]altanserin as a bolus (208 +/- 9 MBq [5.62 +/- 0.25 mCi]) plus constant infusion (65 /- 3 MBq/h [1.76 +/- 0.08 mCi/h]) ranging from 555 to 626 min (615 +/- 24 m in) after injection. PET acquisitions (10-20 min) and Venous blood sampling were performed every 30-60 min throughout the infusion period. Results: Li near regression analysis revealed that time-activity curves for both brain activity and plasma [F-18]altanserin and metabolite concentrations stabiliz ed after about 6 h. This permitted equilibrium modeling and estimation of V -3' (ratio of specific uptake [cortical-cerebellar] to total plasma parent concentration after 6 h). Values of V-3' ranged from 1.57 +/- 0.38 for ante rior cingulate cortex to 1.02 +/- 0.39 for frontal cortex. The binding pote ntial V-3 (ratio of specific uptake to free plasma parent concentration aft er 6 h, using group mean f(1)) was also calculated and ranged from 169 +/- 41 for anterior cingulate cortex to 110 +/- 42 for frontal cortex. From 6 h onward, the rate of change for V-3' and V-3 was only 1.11 +/- 1.69 %/h. Co nclusion: These results demonstrate the feasibility of equilibrium imaging with [F-18]altanserin over more than 5 radioactive half-lives and suggest a method to overcome difficulties associated with lipophilic radiolabeled me tabolites. The stability in V-3 and V-3' once equilibrium is achieved sugge sts that a single PET acquisition obtained at 6 h may provide a reasonable measure of 5-HT2A receptor density.