In vitro and in vivo characterisation of [11C]-DASB: a probe for in vivo measurements of the serotonin transporter by positron emission tomography

Nucl Med Biol. 2002 Jul;29(5):509-15. doi: 10.1016/s0969-8051(02)00316-5.

Abstract

3-Amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, labeled with carbon-11 ([11C]-DASB), is a recently introduced radiotracer for imaging the serotonin transporter (SERT) by positron emission tomography (PET). A series of in vitro and in vivo experiments were performed to further characterise the properties of [11C]-DASB as an in vivo imaging agent for SERT. In vitro binding assays confirmed that DASB binds specifically to SERT with nanomolar affinity and high selectivity over a large number of other receptors, ion-channels and enzymes in the central nervous system. Ex vivo, [11C]-DASB binding in rat brain was shown to be saturable (ED(50) of 56 nmoles/kg), and sensitive to both the number of available SERT binding sites and the number of viable serotonin neurons. Estimates of the radiation dose in man were extrapolated from rat biodistribution data (effective dose 5.5 E-03 mSv/MBq; critical organ --urinary bladder wall). Together with previous studies, the present findings indicate that [11C]-DASB is a very useful radiopharmaceutical for probing changes in SERT densities using PET imaging in the living human brain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacokinetics*
  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbon Radioisotopes / pharmacokinetics*
  • Carrier Proteins / metabolism*
  • Female
  • Fluoxetine / pharmacology
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Radiation Dosage
  • Radiometry / methods
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Sensitivity and Specificity
  • Serotonin Plasma Membrane Transport Proteins
  • Sulfides / pharmacokinetics*
  • Tissue Distribution
  • Tomography, Emission-Computed*
  • Whole-Body Counting

Substances

  • 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile
  • Aniline Compounds
  • Carbon Radioisotopes
  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, rat
  • Sulfides
  • Fluoxetine