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

J Labelled Comp Radiopharm. 2018 Jun 30;61(8):576-585. doi: 10.1002/jlcr.3626. Epub 2018 May 16.


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-d3 )amino)methyl)-4-(3-fluoropropoxy-1,1,2,2,3,3-d6 )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.

Keywords: 18F; PET imaging agent; brain; deuterium; serotonin transporter.

MeSH terms

  • Amines / chemistry*
  • Amines / metabolism
  • Amines / pharmacokinetics
  • Animals
  • Cell Line
  • Deuterium / chemistry*
  • Isotope Labeling
  • Positron-Emission Tomography / methods*
  • Radiochemistry
  • Rats
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Tissue Distribution


  • Amines
  • Serotonin Plasma Membrane Transport Proteins
  • Deuterium