Annals of Nuclear Medicine

, 19:617

Radiosynthesis andin vivo evaluation of11C-Iabeled 1,5-diarylpyrazole derivatives for mapping cyclooxygenases

Authors

  • Yoshihiko Fujisaki
    • Graduate School of Pharmaceutical SciencesKyushu University
  • Kazunori Kawamura
    • Positron Medical CenterTokyo Metropolitan Institute of Gerontology
  • Wei-Fang Wang
    • Positron Medical CenterTokyo Metropolitan Institute of Gerontology
  • Kiichi Ishiwata
    • Positron Medical CenterTokyo Metropolitan Institute of Gerontology
  • Fumihiko Yamamoto
    • Graduate School of Pharmaceutical SciencesKyushu University
  • Takashi Kuwano
    • Graduate School of Medical SciencesKyushu University
  • Mayumi Ono
    • Graduate School of Medical SciencesKyushu University
    • Graduate School of Pharmaceutical SciencesKyushu University
Technical Notes

DOI: 10.1007/BF02985057

Cite this article as:
Fujisaki, Y., Kawamura, K., Wang, W. et al. Ann Nucl Med (2005) 19: 617. doi:10.1007/BF02985057

Abstract

We prepared11C-labeled5-(4-chlorophenyl)-l-(4-methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazole ([11C] 1) and 4-[5-(4-methoxyphenyl)-3-trifluoromethyl-lH-pyrazol-1 -yljbenzenesulfonamide ([11C]2) for imaging COX-1 and COX-2 isoforms, respectively, by positron emission tomography. [11C]l and [11C]2 were synthesized in high radiochemical yields byO-[11C]methylation with [11C]methyl triflate in acetone containing an equivalent of NaOH as a base with respect to the phenolic precursors.In vivo evaluation in rats bearing AH109A hepatoma demonstrated minimal specific binding of [11C]1 to COX-1 in peripheral organs, such as the spleen and small intestine. Carrier-saturable uptake of [11C]2 was found in the spleen, but COX-2-specific binding of [101C]2 was not identifiable in the brain, AH109A hepatoma or other peripheral organs, althoughex vivo autoradiography showed regionally different distribution in the brain and AH 109A. The results suggest that neither [11C]1 nor [11C]2 is a suitable radioligand forin vivo biomarkers of COX enzymes, mainly because of marked non-specific binding.

Key words

cyclooxygenase inhibitorcarbon-11radiosynthesistissue distribution

Copyright information

© Springer 2005