[(11)C]PR04.MZ, a promising DAT ligand for low concentration imaging: Synthesis, efficient (11)C-O-methylation and initial small animal PET studies

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4343-5. doi: 10.1016/j.bmcl.2009.05.090. Epub 2009 May 28.

Abstract

PR04.MZ was designed as a highly selective dopamine transporter inhibitor, derived from natural cocaine. Its binding profile indicates that [(11)C]PR04.MZ may be suited as a PET radioligand for the non-invasive exploration of striatal and extrastriatal DAT populations. As a key feature, its structural design facilitates both, labelling with fluorine-18 at its terminally fluorinated butynyl moiety and carbon-11 at its methyl ester function. The present report concerns the efficient [(11)C]MeI mediated synthesis of [(11)C]PR04.MZ from an O-desmethyl precursor trifluoroacetic acid salt with Rb(2)CO(3) in DMF in up to 95+/-5% labelling yield. A preliminary muPET-experiment demonstrates the reversible, highly specific binding of [(11)C]PR04.MZ in the brain of a male Sprague-Dawley rat.

MeSH terms

  • Animals
  • Azabicyclo Compounds / chemical synthesis*
  • Azabicyclo Compounds / pharmacology
  • Brain / drug effects
  • Carbon Isotopes / chemistry
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Dopamine Plasma Membrane Transport Proteins / chemistry
  • Drug Design
  • Fluorine Radioisotopes / chemistry
  • Magnetic Resonance Imaging / methods
  • Male
  • Methylation
  • Models, Chemical
  • Positron-Emission Tomography / instrumentation
  • Positron-Emission Tomography / methods*
  • Radioligand Assay / instrumentation
  • Radioligand Assay / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tropanes

Substances

  • Azabicyclo Compounds
  • Carbon Isotopes
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes
  • PR04.MZ compound
  • Tropanes