title: Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.
abstract: The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical R(T) (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but was not altered by changes in endogenous 5-HT induced by fenfluramine. These findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, 06516, West Haven, CT 06516, USA. julie.stanley@yale.edu
authors.forename: J K
authors.initials: JK
authors.lastname: Staley
authors.forename: C H
authors.initials: CH
authors.lastname: Van Dyck
authors.forename: P Z
authors.initials: PZ
authors.lastname: Tan
authors.forename: M
authors.initials: M
authors.lastname: Al Tikriti
authors.forename: Q
authors.initials: Q
authors.lastname: Ramsby
authors.forename: H
authors.initials: H
authors.lastname: Klump
authors.forename: C
authors.initials: C
authors.lastname: Ng
authors.forename: P
authors.initials: P
authors.lastname: Garg
authors.forename: R
authors.initials: R
authors.lastname: Soufer
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003903:Deuterium; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D007650:Ketanserin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D010215:Papio; D011854:Radiochemistry; D011985:Receptors, Serotonin / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D011985:Receptors, Serotonin; C071983:altanserin; D007650:Ketanserin; D003903:Deuterium