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

作者：Liu, Futao; Zhu, Lin; Choi, Seok Rye; Ploessl, Karl; Zha, Zhihao; Kung, Hank F.^*

来源：Journal of Labelled Compounds and Radiopharmaceuticals, 2018, 61(8): 576-585.

DOI：10.1002/jlcr.3626

• F-18
• brain
• deuterium
• PET imaging agent
• serotonin transporter

Positron emission tomography imaging of serotonin transporter (SERT) is useful for studying brain diseases with altered serotonergic function. A deuterated imaging agent, ([F-18]2-((2-((bis(methyl-d(3))amino)methyl)-4-(3-fluoropropoxy-1,1,2,2,3,3-d(6))phenyl)thio)aniline, [F-18]D12FPBM, [F-18]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-18]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-18]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-18]FPBM and [F-18]1 showed very similar SERT binding. [F-18]1 might be an excellent candidate for SERT imaging.

• 出版日期2018-6-30
• 单位北京师范大学