Development of a Novel Nonpeptidic (18)F-Labeled Radiotracer for in Vivo Imaging of Oxytocin Receptors with Positron Emission Tomography

J Med Chem. 2016 Mar 10;59(5):1800-17. doi: 10.1021/acs.jmedchem.5b01080. Epub 2016 Feb 3.

Abstract

With the aim of imaging and quantification of oxytocin receptors (OTRs) in living brain using positron emission tomography (PET), we developed a (18)F-labeled small molecule radiotracer and investigated its in vivo pharmacokinetics in mice and pig. [(18)F]6b (KD = 12.3 nM) was radiolabeled by a two-step procedure using a microwave system with radiochemical yields of 26.9 ± 4.7%. Both organ distribution and small animal PET studies revealed limited brain uptake of [(18)F]6b in mouse (mean SUV of 0.04 at 30 min pi). Besides, significant radioactivity uptake in the pituitary gland was observed (SUV of 0.7 at 30 min pi). In a dynamic PET study in one piglet, we detected a higher uptake of [(18)F]6b in the olfactory bulb (SUV of 0.34 at 30 min pi) accompanied by a low uptake in the whole brain. In vitro autoradiographic studies on porcine brain sections indicated interaction of [(18)F]6b with several off-target receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepines / chemical synthesis
  • Benzodiazepines / chemistry*
  • Benzodiazepines / pharmacokinetics*
  • Benzodiazepines / pharmacology
  • Brain / diagnostic imaging
  • Fluorine Radioisotopes / analysis
  • Fluorine Radioisotopes / chemistry*
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Positron-Emission Tomography*
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry*
  • Pyrroles / pharmacokinetics*
  • Pyrroles / pharmacology
  • Radioactive Tracers
  • Receptors, Oxytocin / analysis*
  • Receptors, Oxytocin / antagonists & inhibitors
  • Receptors, Oxytocin / metabolism
  • Swine

Substances

  • Fluorine Radioisotopes
  • Pyrroles
  • Radioactive Tracers
  • Receptors, Oxytocin
  • WAY-162720
  • Benzodiazepines