Synthesis and evaluation of (11)C-labeled (S)-N-[[1-(2-phenylethyl) pyrrolidin-2-yl]methyl]-3-methylthiobenzamide as a PET 5-HT(1A) receptor ligand

Nucl Med Biol. 2002 Aug;29(6):657-63. doi: 10.1016/s0969-8051(02)00305-0.

Abstract

We prepared 5-HT(1A) receptor ligands (S)-N-[[1-(2-phenylethyl)pyrrolidin-2-yl]methyl]-3-[11C]methylthiobenzamide ([11C](S)-PPMMB) (Ki = 4.3 nM) and the less active [(11)C](R)-PPMMB (Ki = 160 nM) by reduction of the disulfide dimer and subsequent [(11)C]methylation of demethyl (S)- and (R)-PPMMB, respectively. Both radioligands showed similar brain distribution in mice with relatively higher affinity for the hippocampus being rich in 5-HT(1A) receptors than for other brain regions. Uptake of [(11)C](S)-PPMMB was not reduced by carrier-loading nor by pretreatment with 5-HT(1A) receptor ligands. [(11)C](S)-PPMMB is therefore not a suitable radioligand for mapping 5-HT(1A) receptors using positron emission tomography.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacokinetics*
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Male
  • Mice
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Reference Values
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sulfides / chemical synthesis*
  • Sulfides / pharmacokinetics*
  • Tissue Distribution
  • Tomography, Emission-Computed

Substances

  • Benzamides
  • N-((1-(2-phenylethyl)pyrrolidin-2-yl)methyl)-3-methylthiobenzamide
  • Radiopharmaceuticals
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Sulfides