Synthesis and in vivo evaluation of [18F]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide as a PET imaging probe for COX-2 expression

Bioorg Med Chem. 2007 Feb 15;15(4):1802-7. doi: 10.1016/j.bmc.2006.11.033. Epub 2006 Nov 29.

Abstract

Synthesis of [18F]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ([18F]celecoxib), a selective COX-2 inhibitor, is achieved via a bromide to [18F]F- exchange reaction. Synthesis of the precursor for radiolabeling was achieved from 4'-methylacetophenone in four steps with 22% overall yield. Under non-radioactive conditions, fluorination was achieved using TBAF in DMSO at 135 degrees C in 80% yield. Synthesis of [18F]celecoxib was achieved using [18F]TBAF in DMSO at 135 degrees C in 10+/-2% yield (EOS) with >99% chemical and radiochemical purities. The specific activity was 120+/-40 mCi/micromol (EOB). [18F]celecoxib was found to be stable in ethanol, however, de[18F]fluorination (6.5%) was observed after 4 h in 10% ethanol-saline solution. Rodent PET studies show bone labeling indicating in vivo de[18F]fluorination of [18F]celecoxib. PET studies in baboon indicated a lower rate of de[18F]fluorination than rat and retention of radioactivity in brain regions consistent with the known distribution of COX-2. A radiolabeling method that can generate consistent high specific activity is needed for routine human use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzenesulfonamides
  • Bone and Bones / diagnostic imaging
  • Brain / diagnostic imaging
  • Cyclooxygenase 2 / analysis*
  • Cyclooxygenase 2 / pharmacokinetics
  • Drug Stability
  • Fluorine Radioisotopes
  • Humans
  • Membrane Proteins / analysis*
  • Membrane Proteins / pharmacokinetics
  • Papio
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Rodentia
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / pharmacokinetics
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • Membrane Proteins
  • Radiopharmaceuticals
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human