Equilibrium modeling of 5-ht2a receptors with [18f]deuteroaltanserin and pet: feasibility of a constant infusion paradigm

Abstract ABSTRACT. [ 18 F]Altanserin has emerged as a promising positron emission tomography (PET) ligand for serotonin-2A (5-HT 2A ) receptors. The deuterium substitution of both of the 2′-hydrogens of altanserin ([ 18 F]deuteroaltanserin) yields a metabolically more stable radiotracer with higher ratios of parent tracer to radiometabolites and increased specific brain uptake than [ 18 F]altanserin. The slower metabolism of the deuterated analog might preclude the possibility of achieving stable plasma and brain activities with a bolus plus constant infusion within a reasonable time frame for an 18 F-labeled tracer (T 1/2 110 min). Thus, the purpose of this study was to test the feasibility in human subjects of a constant infusion paradigm for equilibrium modeling of [ 18 F]deuteroaltanserin with PET. Seven healthy male subjects were injected with [ 18 F]deuteroaltanserin as a bolus plus constant infusion lasting 10 h postinjection. PET acquisitions and venous blood sampling were performed throughout the infusion period. Linear regression analysis revealed that time-activity curves for both specific brain uptake and plasma [ 18 F]deuteroaltanserin concentration stabilized after about 5 h. This permitted equilibrium modeling and estimation of V ′ 3 (ratio of specific uptake to total plasma parent concentration) and the binding potential V 3 (ratio of specific uptake to free plasma parent concentration). Cortical/cerebellar ratios were increased by 26% relative to those we previously observed with [ 18 F]altanserin using similar methodology in a somewhat older subject sample. These results demonstrate feasibility of equilibrium imaging with [ 18 F]deuteroaltanserin and suggest that it may be superior to [ 18 F]altanserin as a PET radioligand.