Comparison of [F-18]altanserin and [F-18]deuteroaltanserin for PET imagingof serotonin(2A) receptors in baboon brain: pharmacological studies

The regional distribution in brain, distribution volumes, and pharmacologic al specificity of the PET 5-HT2A receptor radiotracer [F-18]deuteroaltanser in were evaluated and compared to those of its non-deuterated derivative [F -18]altanserin. Both radiotracers were administered to baboons by bolus plu s constant infusion and PET images were acquired up to 8 h. The time-activi ty curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between rad iotracers; nevertheless, total cortical R-T (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [F-1 8]deuteroaltanserin than for [F-18]altanserin. In contrast, the binding pot ential (B-max/K-D) was similar between radiotracers. [F-18]Deuteroaltanseri n cortical activity was displaced by the 5-HT2A receptor antagonist SR 4634 9B but was not altered by changes in endogenous 5-HT induced by fenfluramin e. These findings suggest that [F-18]deuteroaltanserin is essentially equiv alent to [F-18]altanserin for 5-HT2A receptor imaging in the baboon. (C) 20 01 Elsevier Science Inc. All rights reserved.