A new single-photon emission computed tomography (SPECT) imaging agent for serotonin transporters: [(125)I]Flip-IDAM, (2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol

Bioorg Med Chem Lett. 2013 Feb 1;23(3):869-72. doi: 10.1016/j.bmcl.2012.11.043. Epub 2012 Dec 2.

Abstract

New ligands for in vivo brain imaging of serotonin transporter (SERT) with single photon emission tomography (SPECT) were prepared and evaluated. An efficient synthesis and radiolabeling of a biphenylthiol, FLIP-IDAM, 4, was accomplished. The affinity of FLIP-IDAM was evaluated by an in vitro inhibitory binding assay using [(125)I]-IDAM as radioligand in rat brain tissue homogenates (K(i) = 0.03 nM). New [(125)I]Flip-IDAM exhibited excellent binding affinity to SERT binding sites with a high hypothalamus to cerebellum ratio of 4 at 30 min post iv injection. The faster in vivo kinetics for brain uptake and a rapid washout from non-specific regions provide excellent signal to noise ratio. This new agent, when labeled with (123)I, may be a useful imaging agent for mapping SERT binding sites in the human brain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzylamines / chemical synthesis
  • Benzylamines / chemistry*
  • Chromatography, High Pressure Liquid
  • Iodine Radioisotopes / chemistry*
  • Molecular Structure
  • Protein Binding
  • Radiopharmaceuticals / chemistry*
  • Rats
  • Serotonin Plasma Membrane Transport Proteins / chemistry*
  • Sulfides / chemical synthesis
  • Sulfides / chemistry*
  • Tomography, Emission-Computed, Single-Photon*

Substances

  • (2-((2-((dimethylamino)methyl)-4-iodophenyl)thio)phenyl)methanol
  • Benzylamines
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Serotonin Plasma Membrane Transport Proteins
  • Sulfides