Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate

Appl Radiat Isot. 2006 May;64(5):570-3. doi: 10.1016/j.apradiso.2005.12.003. Epub 2006 Jan 20.

Abstract

Recently, the pyrazolopyrimidine, [11C] N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide (DPA-713) has been reported as a new promising marker for the study of peripheral benzodiazepine receptors with positron emission tomography. In the present study, DPA-713 has been labelled from the corresponding nor-analogue using [11C]methyl triflate (CH3OTf). Conditions for HPLC were also modified to include physiological saline (aq. 0.9% NaCl)/ethanol:60/40 as mobile phase making it suitable for injection. The total time of radiosynthesis, including HPLC purification, was 18-20 min. This reported synthesis of [11C]DPA-713, using [11C]CH3OTf, resulted in an improved radiochemical yield (30-38%) compared to [11C]methyl iodide (CH3I) (9) with a simpler purification method. This ultimately enhances the potential of [11C]DPA-713 for further pharmacological and clinical evaluation. These improvements make this radioligand more suitable for automated synthesis which is of benefit where multi-dose preparations and repeated syntheses of radioligand are required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / chemistry
  • Carbon Radioisotopes / chemistry*
  • Chromatography, High Pressure Liquid
  • Isotope Labeling / methods
  • Ligands
  • Mesylates / chemistry*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Receptors, GABA-A / metabolism*
  • Spectrophotometry, Ultraviolet

Substances

  • Acetamides
  • Carbon Radioisotopes
  • Ligands
  • Mesylates
  • N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide
  • Pyrazoles
  • Pyrimidines
  • Receptors, GABA-A
  • methyl triflate