Synthesis and evaluation of C-11, F-18 and I-125 small molecule radioligands for detecting oxytocin receptors

Bioorg Med Chem. 2012 Apr 15;20(8):2721-38. doi: 10.1016/j.bmc.2012.02.019. Epub 2012 Feb 25.


Compounds 1-4 were synthesized and investigated for selectivity and potency for the oxytocin receptor (OTR) to determine their viability as radioactive ligands. Binding assays determined 1-4 to have high binding affinity for both the human and rodent OTR and also have high selectivity for the human OTR over human vasopressin V1a receptors (V1aR). Inadequate selectivity for OTR over V1aR was found for rodent receptors in all four compounds. The radioactive (C-11, F-18, and I-125) derivatives of 1-4 were synthesized and investigated for use as autoradiography and positron emission tomography (PET) ligands. Receptor autoradiography performed with [(125)I]1 and [(125)I]2 on rodent brain slices provided the first small molecule radioligand images of the OTR and V1aR. Biodistribution studies determined [(125)I]1 and [(125)I]2 were adequate for in vivo peripheral investigations, but not for central investigations due to low uptake within the brain. A biodistribution study with [(18)F]3 suggested brain uptake occurred slowly over time. PET imaging studies with [(18)F]3 and [(11)C]4 using a rat model provided insufficient uptake in the brain over a 90 and 45 min scan times respectively to merit further investigations in non-human primates.

Publication types

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

MeSH terms

  • Animals
  • Arvicolinae
  • Autoradiography
  • Binding, Competitive
  • Carbon Isotopes
  • Cell Line
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Iodine Radioisotopes
  • Ligands
  • Molecular Structure
  • Molecular Weight
  • Piperidines* / chemical synthesis
  • Piperidines* / pharmacokinetics
  • Positron-Emission Tomography
  • Quinolines* / chemical synthesis
  • Quinolines* / pharmacokinetics
  • Radioligand Assay
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Oxytocin / analysis*
  • Structure-Activity Relationship
  • Tissue Distribution


  • Carbon Isotopes
  • Fluorine Radioisotopes
  • Iodine Radioisotopes
  • Ligands
  • Piperidines
  • Quinolines
  • Radiopharmaceuticals
  • Receptors, Oxytocin