PET quantification of 5-HT(2A) receptors in the human brain: A constant infusion paradigm with [18F]altanserin

Abstract

[18F]altanserin has been used to label serotonin 5-HT(2A) receptors, which are believed to be important in the pathophysiology of schizophrenia and depression. The purpose of this study was to test the feasibility of a constant infusion paradigm for equilibrium modeling of [18F]altanserin with PET. Kinetic modeling with [18F]altanserin may be hampered by the presence of lipophilic radiometabolites observed in plasma after intravenous administration. Methods: Eight healthy volunteers were injected with [18F]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 min) after injection. PET acquisitions (10-20 min) and venous blood sampling were performed every 30-60 min throughout the infusion period. Results: Linear regression analysis revealed that time-activity curves for both brain activity and plasma [18F]altanserin and metabolite concentrations stabilized after about 6 h. This permitted equilibrium modeling and estimation of V3' (ratio of specific uptake [cortical- cerebellar] to total plasma parent concentration after 6 h). Values of V3' ranged from 1.57 ± 0.38 for anterior cingulate cortex to 1.02 ± 0.39 for frontal cortex. The binding potential V3 (ratio of specific uptake to free plasma parent concentration after 6 h, using group mean f1) 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 V3' and V3 was only 1.11 ± 1.69 %/h. Conclusion: These results demonstrate the feasibility of equilibrium imaging with [18F]altanserin over more than 5 radioactive half-lives and suggest a method to overcome difficulties associated with lipophilic radiolabeled metabolites. The stability in V3 and V3' once equilibrium is achieved suggests that a single PET acquisition obtained at 6 h may provide a reasonable measure of 5-HT(2A) receptor density.