Synthesis and preliminary evaluation of 4-hydroxy-6-(3-[11C]methoxyphenethyl)pyridazin-3(2H)-one, a 11C-labeled d-amino acid oxidase (DAAO) inhibitor for PET imaging

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127326. doi: 10.1016/j.bmcl.2020.127326. Epub 2020 Jun 9.


Selective DAAO inhibitors have demonstrated promising therapeutic effects in clinical studies, including clinically alleviating symptoms of schizophrenic patients and ameliorating cognitive function in Alzheimer's patients with early phase. Herein we report the synthesis and preliminary evaluation of a 11C-labeled positron emission tomography ligand based on a DAAO inhibitor, DAO-1903 (8). 11C-Isotopologue of 8 was prepared in high radiochemical yield with high radiochemical purity (>99%) and high molar activity (>37 GBq/µmol). In vitro autoradiography studies indicated that the ligand possessed high in vitro specific binding to DAAO, while in vivo dynamic PET studies demonstrated that [11C]8 failed to cross the blood-brain barrier possibly due to moderate brain efflux mechanism. Further chemical scaffold optimization is necessary to overcome limited brain permeability and improve specific binding.

Keywords: Carbon-11; Cerebellum function; Positron emission tomography (PET); Schizophrenia; d-Amino acid oxidase (DAAO).

Publication types

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

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • D-Amino-Acid Oxidase / antagonists & inhibitors
  • D-Amino-Acid Oxidase / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Molecular Structure
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship


  • Radiopharmaceuticals
  • D-Amino-Acid Oxidase