[18F]fluoroalkyl analogues of the potent 5-HT1A antagonist WAY 100635: radiosyntheses and in vivo evaluation

Nucl Med Biol. 1996 May;23(4):487-90. doi: 10.1016/0969-8051(96)00026-1.

Abstract

Two analogues of the potent 5-HT1A antagonist WAY 100635 have been synthesized and radiolabelled with 18F, namely N-[2-[4-(2-2'-[18F] fluoroethoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xan e carboxamide ([18F]FEC) and N-[2-[4-(2-3'-[18F] fluoropropoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cycloh exa ne carboxamide ([18F]FPC). Biodistribution studies in rats showed selective uptake of both radiotracers in regions known to be rich in 5-HT1A receptors following i.v. injection. The ratio of radioactivity in hippocampus to that in the cerebellum was 5.5 (for [18F]FEC) and 7.5 (for [18F]FPC) at 60 min postinjection. Regional brain heterogeneity of radioactivity could be abolished by pretreatment with WAY 100635 and FPC but was unaffected by pretreatment with a variety of drugs including ketanserin, sulpiride, and SCH 23390. These results are compared vis-a-vis with those obtained using [11C]WAY 100635 to evaluate [18F]FEC and [18F]FPC as potential radiotracers for imaging 5-HT1A receptors by positron emission tomography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorine Radioisotopes / chemistry
  • Fluorine Radioisotopes / pharmacokinetics*
  • Isotope Labeling / methods
  • Male
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacokinetics*
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacokinetics*
  • Radiochemistry / methods
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / pharmacokinetics*
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • N-(2-(4-(2-(2'-fluoroethoxy)phenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide
  • N-(2-(4-(2-(3'-fluoropropoxy)phenyl)-1-piperazinyl)ethyl)-N-(2-pyridnyl)cyclohexane carboxamide
  • Piperidines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists