Equilibrium modeling of 5-HT2A receptors with [F-18]deuteroaltanserin and PET: Feasibility of a constant infusion paradigm

[F-18]Altanserin has emerged as a promising positron emission tomography (P ET) ligand for serotonin-2A (5 HT2A) receptors. The deuterium substitution of both of the 2'-hydrogens of altanserin ([F-18]deuteroaltanserin) yields a metabolically more stable radiotracer with higher ratios of parent tracer to radiometabolites and increased specific brain uptake than [F-18]altanse rin. The slower metabolism of the deuterated analog might preclude the poss ibility of achieving stable plasma and brain activities with a bolus plus c onstant infusion within a reasonable time frame for an F-18-labeled tracer (T-1/2 110 min). Thus, the purpose of this study was to test the feasibilit y in human subjects of a constant infusion paradigm for equilibrium modelin g of [F-18]deuteroaltanserin with PET. Seven healthy male subjects were inj ected with [F-18]deuteroaltanserin as a bolus plus constant infusion lastin g 10 h postinjection. PET acquisitions and venous blood sampling were perfo rmed throughout the infusion period. Linear regression analysis revealed th at time-activity curves for both specific brain uptake and plasma [F-18]deu teroaltanserin concentration stabilized after about 5 h, This permitted equ ilibrium modeling and estimation of V-3' (ratio of specific uptake to total plasma parent concentration) and the binding potential V-3 (ratio of speci fic uptake to free plasma parent concentration), Cortical/cerebellar ratios were increased by 26% relative to those we previously observed with [F-18] altanserin using similar methodology in a somewhat older subject sample. Th ese results demonstrate feasibility of equilibrium imaging with [F-18]deute roaltanserin and suggest that it may be superior to [F-18]altanserin as a P ET radioligand. NUCL MED BIOL 27;8:715-722, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.