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Deuterium‐substituted 2‐(2′‐((dimethylamino)methyl)‐4′‐[ 18 F](fluoropropoxy)phenylthio)benzenamine as a serotonin transporter imaging agent
Author(s) -
Liu Futao,
Zhu Lin,
Choi Seok Rye,
Plössl Karl,
Zha Zhihao,
Kung Hank F.
Publication year - 2018
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3626
Subject(s) - serotonin transporter , chemistry , serotonergic , serotonin , imaging agent , biodistribution , striatum , in vivo , hypothalamus , stereochemistry , medicine , in vitro , biochemistry , receptor , biology , microbiology and biotechnology , dopamine
Positron emission tomography imaging of serotonin transporter (SERT) is useful for studying brain diseases with altered serotonergic function. A deuterated imaging agent, ([ 18 F]2‐((2‐((bis(methyl‐ d 3 )amino)methyl)‐4‐(3‐fluoropropoxy‐1,1,2,2,3,3‐ d 6 )phenyl)thio)aniline, [ 18 F]D12FPBM, [ 18 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 [ 18 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 [ 18 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; [ 18 F]FPBM and [ 18 F] 1 showed very similar SERT binding. [ 18 F] 1 might be an excellent candidate for SERT imaging.