title: PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.
abstract: [18F]altanserin has been used to label serotonin 5-HT2A 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.
  
  
  CONCLUSIONS
  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-HT2A receptor density.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: P Z
authors.initials: PZ
authors.lastname: Tan
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: L A
authors.initials: LA
authors.lastname: Amici
authors.forename: P K
authors.initials: PK
authors.lastname: Garg
authors.forename: C K
authors.initials: CK
authors.lastname: Ng
authors.forename: R
authors.initials: R
authors.lastname: Soufer
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D007650:Ketanserin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016014:Linear Models; D008297:Male; D011985:Receptors, Serotonin / Q000032:analysis*; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D011985:Receptors, Serotonin; C071983:altanserin; D007650:Ketanserin