High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635

Nucl Med Biol. 1998 May;25(4):343-50. doi: 10.1016/s0969-8051(97)00229-1.

Abstract

No-carrier-added 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) was synthesized by nucleophilic substitution of the corresponding nitro compound in the presence of Kryptofix 222 and K2CO3 by microwave heating (3 min, 500 W) using a remotely controlled radiosynthesis. Baseline separation of p-[18F]MPPF from the nitro derivative was performed on a semipreparative HPLC C18 column. After Sep-Pak formulation, the radiopharmaceutical was obtained with a radiochemical yield of 25% (EOS) in about 70 min. Specific radioactivity averaged between 1-5 Ci/micromol EOS. Labelling of the ortho and meta derivatives was also attempted. Brain uptake of p-[18F]MPPF was studied with PET on fluothane-anesthetized cats. Following intravenous injection of p-[18F]MPPF, high accumulation of radioactivity was observed in the hippocampus and cerebral cortex. Low levels of radioactivity were observed in cerebellum. At 30 min, the mean hippocampus/cerebellum and cortex/cerebellum ratios were 5 and 3.8, respectively. The accumulation of the tracer was blocked by prior administration of reference WAY-100635, demonstrating the specificity of the ligand.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cats
  • Chromatography, High Pressure Liquid
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Molecular Structure
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacokinetics*
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacokinetics*
  • Quality Control
  • Radioligand Assay
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics*
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / pharmacokinetics*
  • Tomography, Emission-Computed*

Substances

  • 4-fluoro-N-(2-(1-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinylbenzamide
  • Fluorine Radioisotopes
  • Piperazines
  • Pyridines
  • Radiopharmaceuticals
  • Serotonin Antagonists
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide