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Identification of PET radiometabolites by cytochrome P450, UHPLC/Q-ToF-MS and fast radio-LC: applied to the PET radioligands [11C]flumazenil, [18F]FE-PE2I, and [11C]PBR28

Analytical and Bioanalytical Chemistry volume 405, pages 1303–1310 (2013)Cite this article

Abstract

A general method is presented for the identification of radiometabolites in plasma of human and monkey subjects after administration of positron emission tomography (PET) radioligands. The radiometabolites are first produced in vitro, using liver microsomes, subsequently separated using fast radio-liquid chromatography (radio-LC), and individually collected and identified by ultra high-performance liquid chromatography/quadrupole-time of flight-mass spectrometry in MS and MSE mode. Fast radio-LC provided superior resolution compared to conventional radio-LC, resulting in separation of a greater number of metabolites. The radiometabolites produced in vivo are then compared to and identified based on the in vitro results. This approach was applied to three PET radioligands, [11C]flumazenil, [18F]FE-PE2I, and [11C]PBR28, resulting in the identification of five, two, and one radiometabolites, respectively. This procedure can easily be adopted to identify the radiometabolites produced in vivo from a variety of PET radioligands.

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Acknowledgments

The authors thank all the members of the PET group at Karolinska Institutet for their kind assistance during this study.

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Affiliations

  1. Department of Clinical Neuroscience, Center for Psychiatric Research, Karolinska Institutet, Stockholm, 171 76, Sweden

    Nahid Amini, Ryuji Nakao, Magnus Schou & Christer Halldin

  2. AstraZeneca, Research & Development, Innovative Medicines, CNSP iMed, 151 85, Södertälje, Sweden

    Magnus Schou

Authors
  1. Nahid Amini
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  2. Ryuji Nakao
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  3. Magnus Schou
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  4. Christer Halldin
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Correspondence to Nahid Amini.

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Amini, N., Nakao, R., Schou, M. et al. Identification of PET radiometabolites by cytochrome P450, UHPLC/Q-ToF-MS and fast radio-LC: applied to the PET radioligands [11C]flumazenil, [18F]FE-PE2I, and [11C]PBR28. Anal Bioanal Chem 405, 1303–1310 (2013). https://doi.org/10.1007/s00216-012-6541-2

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  • DOI: https://doi.org/10.1007/s00216-012-6541-2

Keywords

  • Positron emission tomography (PET) radioligands
  • Radiometabolites
  • Fast radio-liquid chromatography (radio-LC)
  • Ultra high-performance liquid chromatography/quadrupole-time of flight-mass spectrometry (UHPLC/Q-ToF-MS)
  • Cytochrome P450