Radiosynthesis and mouse brain distribution studies of [11C] CP-126,998: a PET ligand for in vivo study of acetylcholinesterase

Nucl Med Biol. 2002 Jul;29(5):547-52. doi: 10.1016/s0969-8051(02)00299-8.

Abstract

The selective, reversible acetylcholinesterase inhibitor 5,7-Dihydro-7-methyl-3- [2-[1-(phenylmethyl]-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol3-6-one (CP-126,998) was labeled with C-11 iodomethane via base-promoted alkylation of the lactam nitrogen. [11C] CP-126,998 was synthesized in good radiochemical yield (13-29% non-decay corrected) and high specific radioactivity (177-418 GBq/micromol). In vivo mouse biodistribution studies reveal [11C] CP-126,998 to localize preferentially in striatal tissue, a region known to be rich in acetylcholinesterase. Competitive blocking studies using a variety of acetylcholinesterase inhibitors (diisopropylfluorophosphate, tacrine, CP-118,954) verified the specificity of the PET radiotracer for brain acetylcholinesterase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Carbon Radioisotopes / pharmacokinetics*
  • Isoflurophate / pharmacology
  • Isotope Labeling / methods
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / pharmacokinetics*
  • Ligands
  • Male
  • Mice
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Reference Values
  • Tissue Distribution
  • Tomography, Emission-Computed

Substances

  • CP 126,998
  • Carbon Radioisotopes
  • Isoxazoles
  • Ligands
  • Piperidines
  • Radiopharmaceuticals
  • Isoflurophate
  • Acetylcholinesterase