Nuclear Medicine and Biology
Volume 33, Issue 8 , Pages 1013-1019 , November 2006

Species differences in metabolites of PET ligands: serotonergic 5-HT1A receptor antagonists 3-trans-FCWAY and 3-cis-FCWAY

  • Ying Ma

      Affiliations

    • PET Radiochemistry Group, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
    • ,
  • Lixin Lang

      Affiliations

    • PET Radiochemistry Group, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
    • ,
  • Dale Kiesewetter

      Affiliations

    • PET Radiochemistry Group, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
    • ,
  • Elaine Jagoda

      Affiliations

    • PET Radiochemistry Group, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA
    • ,
  • William C. Eckelman

      Affiliations

    • Molecular Tracer LLC, Bethesda, MD 20892, USA
    • Corresponding Author InformationCorresponding author.

Received 27 June 2006 ,Revised 28 September 2006 ,Accepted 28 September 2006.

References 

  1. Kroeze WK, Kristiansen K, Roth BL. Molecular biology of serotonin receptors — structure and function at the molecular level. Curr Top Med Chem. 2002;2:507–528
  2. Cliffe IA. A retrospect on the discovery of WAY-100635 and the prospect for improved 5-HT(1A) receptor PET radioligands. Nucl Med Biol. 2000;27:441–447
  3. Cliffe IA, Brightwell CI, Fletcher A, Forster EA, Mansell HL, et al. (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide [(S)-WAY-100135]: a selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. J Med Chem. 1993;36:1509–1510
  4. Fletcher A, Bill DJ, Cliffe IA, Dover GM, Forster EA, et al. WAY100135: a novel, selective antagonist at pre-synaptic and post-synaptic 5-HT1A receptors. Eur J Pharmacol. 1993;283–291
  5. Mathis CA, Simpson NR, Mahmood K, Kinahan PE, Mintun MA. [11C]WAY 100635: a radioligand for imaging 5-HT1A receptors with positron emission tomography. Life Sci. 1994;PL403–PL407
  6. Pike VW, McCarron JA, Lammertsma AA, Hume SP, Poole K, et al. First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635. Eur J Pharmacol. 1995;283:R1–R3
  7. Pike VW, McCarron JA, Lammertsma AA, Osman S, Hume SP, et al. Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11C]WAY-100635. Eur J Pharmacol. 1996;301:R5–R7
  8. Lang L, Jagoda E, Schmall B, Vuong BK, Adams HR, et al. The development of fluorine-18-labeled 5-HT1A antagonists. J Med Chem. 1999;42:1576–1586
  9. Carson RE, Lang L, Watabe H, Der MG, Adams HR, et al. PET evaluation of [(18)F]FCWAY, an analog of the 5-HT(1A) receptor antagonist, WAY-100635. Nucl Med Biol. 2000;27:493–497
  10. Lang L, Jagoda E, Schmall B, Sassaman M, Ma Y, et al. Fluoro analogs of WAY-100635 with varying pharmacokinetics properties. Nucl Med Biol. 2000;27:457–462
  11. Lang L, Jagoda E, Ma Y, Sassaman MB, Eckelman WC. Synthesis and in vivo biodistribution of F-18 labeled 3-cis-, 3-trans-, 4-cis-, and 4-trans-fluorocyclohexane derivatives of WAY 100635. Bioorg Med Chem. 2006;14:3737–3748
  12. Ma Y, Kiesewetter DO, Lang L, Der M, Huang BX, Carson RE, et al. Determination of [18F]FC-WAY, [18F]FP-TZTP, and their metabolites in plasma using rapid and efficient liquid–liquid and solid phase extractions. Nucl Med Biol. 2003;30(3):235–240
  13. Ma Y, Kiesewetter D, Lang L, Eckelman WC. Application of LC-MS to the analysis of new radiopharmaceuticals. Mol Imaging Biol. 2003;5(6):397–403
  14. Ma Y, Lang L, Kiesewetter DO, Jagoda E, Sassaman MB, et al. Liquid chromatography–tandem mass spectrometry identification of metabolites of two 5-HT1A antagonists, N-[2-[4-(2-methoxylphenyl)piperazino]ethyl]-N-(2-pyridyl) trans- and cis-4-fluorocyclohexanecarboxamide, produced by human and rat hepatocytes. J Chromatogr B Biomed Sci Appl. 2001;755:47–56
  15. Ma Y, Lang L, Kiesewetter DO, Eceklman WC. LC/MS identification of metabolites of three derivatives of 5-HT1A antagonist produced by human and rat hepatocytes. J Chromatogr B. 2002;780:99–110
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PII: S0969-8051(06)00193-4

doi: 10.1016/j.nucmedbio.2006.09.006

Nuclear Medicine and Biology
Volume 33, Issue 8 , Pages 1013-1019 , November 2006

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