Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.
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.
Staley
J K
JK
Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, 06516, West Haven, CT 06516, USA. julie.stanley@yale.edu
Van Dyck
C H
CH
Tan
P Z
PZ
Al Tikriti
M
M
Ramsby
Q
Q
Klump
H
H
Ng
C
C
Garg
P
P
Soufer
R
R
Baldwin
R M
RM
Innis
R B
RB
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
D005462:Fluorine Radioisotopes; D011985:Receptors, Serotonin; C071983:altanserin; D007650:Ketanserin; D003903:Deuterium