Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

European Radiology volume 22, pages1465–1478(2012)Cite this article

Abstract

The evaluation of drug pharmacodynamics and early tumour response are integral to current clinical trials of novel cancer therapeutics to explain or predict long term clinical benefit or to confirm dose selection. Tumour vascularity assessment by positron emission tomography could be viewed as a generic pharmacodynamic endpoint or tool for monitoring response to treatment. This review discusses methods for semi-quantitative and quantitative assessment of tumour vascularity. The radioligands and radiotracers range from direct physiological functional tracers like [15O]-water to macromolecular probes targeting integrin receptors expressed on neovasculature. Finally we make recommendations on ways to incorporate such measurements of tumour vascularity into early clinical trials of novel therapeutics.

Key Points

• [ 15 O]-water is the gold standard for blood flow/tissue perfusion with PET

• In some instances dynamic [ 18 F]-FDG uptake may be used to estimate perfusion

• Radiopharmaceuticals that target integrins are now being evaluated for measuring tumour vascularity

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Acknowledgements

The authors thank the Society of Nuclear Medicine and Dr Matthew Morrison for allowing permission to reprint the data in Fig. 3. We would also like to acknowledge the Experimental Cancer Medicine Centre Imaging Steering Committee and Secretariat for supporting the workshop on tumour vascularity in May 2010 and coordinating activities, and all of the speakers and delegates who contributed to the meeting. The Experimental Cancer Medicine Centre Initiative is jointly funded by Cancer Research UK, the National Institute for Health Research in England and the Departments of Health for Scotland, Wales and Northern Ireland.

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Affiliations

  1. Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, MRC Cyclotron Building, Hammersmith Hospital Campus, London, W12 0NN, UK

    Eric O. Aboagye & Laura M. Kenny

  2. Radiology Department, University of Cambridge, Addenbrooke’s Hospital, Box 218, Cambridge, CB2 0QQ, UK

    Fiona J. Gilbert

  3. NCRI PET Research Network, Aberdeen Bioimaging Centre, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK

    Ian N. Fleming

  4. Department of Nuclear Medicine, Technische Universität Munchen, Klinikum rechts der Isar, Ismaninger str. 22, 81675, Munich, Germany

    Ambros J. Beer

  5. Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK

    Vincent J. Cunningham

  6. Division of Imaging Sciences, PET Imaging Centre, St. Thomas’ Hospital, Lower Ground Floor, Lambeth Wing, London, SE1 7EH, UK

    Paul K. Marsden

  7. INSERM National Institute of Health and Clinical Sciences LaTIM, CHU Morvan, Bat2bis 5 Avenue Foch, 29609, Brest, France

    Dimitris Visvikis

  8. Division of Imaging Sciences, The Rayne Institute, St. Thomas’ Hospital, 4th Floor, Lambeth Wing, London, SE1 7EH, UK

    Antony D. Gee

  9. Institute of Nuclear Medicine, University College London, University College Hospital, 250 Euston Road, London, NW1 2BU, UK

    Ashley M. Groves

  10. KCL Division of Imaging, Sciences and Biomedical Engineering, PET Imaging Centre, St. Thomas’ Hospital, London, SE1 7EH, UK

    Gary J. Cook

  11. University of Washington, 222 Old Fisheries Center (FIS), Box 357987, Seattle, WA, 98195-7987, USA

    Paul E. Kinahan

  12. Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK

    Melvyn Myers

  13. Imaging Technology Development Branch, Cancer Imaging Program, EPN, Room 6066, 6130 Executive Boulevard, Rockville, MD, 20852-7412, USA

    Larry Clarke

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  1. Eric O. Aboagye
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  13. Melvyn Myers
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  14. Larry Clarke
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Corresponding author

Correspondence to Eric O. Aboagye.

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L. Clarke represents on behalf of the Experimental Cancer Medicine Centre 13 Imaging Network Group.

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Aboagye, E.O., Gilbert, F.J., Fleming, I.N. et al. Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials. Eur Radiol 22, 1465–1478 (2012). https://doi.org/10.1007/s00330-011-2311-3

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Keywords

  • Tumour vascularity
  • Positron emission tomography
  • Angiogenesis
  • [15O]-water
  • Integrin receptor ligand