Deuterium‐substituted 2‐(2′‐((dimethylamino)methyl)‐4′‐[¹⁸F](fluoropropoxy)phenylthio)benzenamine as a serotonin transporter imaging agent

Abstract

Positron emission tomography imaging of serotonin transporter (SERT) is useful for studying brain diseases with altered serotonergic function. A deuterated imaging agent, ([ F]2-((2-((bis(methyl-d )amino)methyl)-4-(3-fluoropropoxy-1,1,2,2,3,3-d )phenyl)thio)aniline, [ F]D12FPBM, [ F]1), was prepared as a new chemical entity. The deuterated agent, 1, showed excellent binding affinity to SERT; Ki was 0.086 nM, comparable with the undeuterated FPBM. In vivo biodistribution studies in rats with [ F]1 showed good brain uptake (1.09% dose/g at 2 min post injection) and high specific uptake into the hypothalamus (HY) as compared with cerebellum (CB) (HY/CB = 7.55 at 120 min), suggesting a specific localization to SERT binding sites. Regional brain distribution in rats provided clear indication that [ F]1 concentrated in the hypothalamus, hippocampus, and striatum, areas with a high SERT density. Results indicate that very little D to H substitution effect was found; [ F]FPBM and [ F]1 showed very similar SERT binding. [ F]1 might be an excellent candidate for SERT imaging.