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Amyloid imaging in cognitively normal older adults: comparison between 18F-flutemetamol and 11C-Pittsburgh compound B

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Preclinical, or asymptomatic, Alzheimer’s disease (AD) refers to the presence of positive AD biomarkers in the absence of cognitive deficits. This research concept is being applied to define target populations for clinical drug development. In a prospective community-recruited cohort of cognitively intact older adults, we compared two amyloid imaging markers within subjects: 18F-flutemetamol and 11C-Pittsburgh compound B (PIB).

Methods

In 32 community-recruited cognitively intact older adults aged between 65 and 80 years, we determined the concordance between binary classification based on 18F-flutemetamol versus 11C-PIB according to semiquantitative assessment (standardized uptake value ratio in composite cortical volume, SUVRcomp) and, alternatively, according to visual reads. We also determined the correlation between 18F-flutemetamol and 11C-PIB SUVR and evaluated how this was affected by the reference region chosen (cerebellar grey matter versus pons) and the use of partial volume correction (PVC) in this population.

Results

Binary classification based on semiquantitative assessment was concordant between 18F-flutemetamol and 11C-PIB in 94 % of cases. Concordance of blinded binary visual reads between tracers was 84 %. The Spearman correlation between 18F-flutemetamol and 11C-PIB SUVRcomp with cerebellar grey matter as reference region was 0.84, with a slope of 0.98. Correlations in neocortical regions were significantly lower with the pons as reference region. PVC improved the correlation in striatum and medial temporal cortex.

Conclusion

For the definition of preclinical AD based on 18F-flutemetamol, concordance with 11C-PIB was highest using semiquantitative assessment with cerebellar grey matter as reference region.

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Acknowledgements

We would like to thank the staff of Nuclear Medicine, Neurology, and Radiology at the University Hospitals Leuven. Special thanks to Carine Schildermans, Dorien Timmers, Kwinten Porters and Mieke Steukers for help with the study.

Compliance with ethical standards

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Funding

This study was funded by the Foundation for Alzheimer Research SAO-FRMA (grant numbers 09013, 11020, 13007); Research Foundation Flanders (grant number G.0660.09); KU Leuven (grant numbers OT/08/056, OT/12/097); IWT VIND; IWT TGO BioAdapt AD; Belspo IAP (grant number P7/11); Research Foundation Flanders senior clinical investigator grant to R.V. and K.V.L.; Research Foundation Flanders doctoral fellowship to K.A; and KH is supported by the Research Fund KU Leuven (grant numbers OT/11/087 and CREA/14/023). 18F-Flutemetamol was provided by GE Healthcare free of charge for this academic investigator-driven trial.

Conflicts of interest

Katarzyna Adamczuk, Jolien Schaeverbeke, Natalie Nelissen, Veerle Neyens, Mathieu Vandenbulcke, Karolien Goffin, Johan Lilja, Kelly Hilven, Patrick Dupont and Koen Van Laere declare that they have no conflicts of interest. Rik Vandenberghe was the PI of the phase 1 and 2 18F-flutemetamol trials. UZ Leuven has had a clinical trial agreement for these trials with GE Healthcare. RV has a consultancy agreement with GE Healthcare. 18F-Flutemetamol was provided by GE Healthcare for the conduct of reported investigator-driven trial free of cost.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Laboratory for Cognitive Neurology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    Katarzyna Adamczuk, Jolien Schaeverbeke, Natalie Nelissen, Veerle Neyens, Patrick Dupont & Rik Vandenberghe

  2. Alzheimer Research Centre KU Leuven, Leuven Institute of Neuroscience and Disease, Herestraat 49, 3000, Leuven, Belgium

    Katarzyna Adamczuk, Jolien Schaeverbeke, Veerle Neyens, Patrick Dupont, Koen Van Laere & Rik Vandenberghe

  3. Department of Psychiatry, Oxford University, OX3 7JX, Oxford, UK

    Natalie Nelissen

  4. Old Age Psychiatry Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Mathieu Vandenbulcke

  5. Nuclear Medicine and Molecular Imaging Department, KU Leuven and University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Karolien Goffin & Koen Van Laere

  6. GE Healthcare, Björkgatan 30, 753 23, Uppsala, Sweden

    Johan Lilja

  7. Uppsala University, Department of Surgical Sciences, Radiology, Uppsala University Hospital, 751 85, Uppsala, Sweden

    Johan Lilja

  8. Laboratory for Neuroimmunology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    Kelly Hilven

  9. Neurology Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Rik Vandenberghe

Authors
  1. Katarzyna Adamczuk
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  2. Jolien Schaeverbeke
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  3. Natalie Nelissen
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  4. Veerle Neyens
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  5. Mathieu Vandenbulcke
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  6. Karolien Goffin
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  7. Johan Lilja
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  8. Kelly Hilven
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  9. Patrick Dupont
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  10. Koen Van Laere
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  11. Rik Vandenberghe
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Corresponding author

Correspondence to Rik Vandenberghe.

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Adamczuk, K., Schaeverbeke, J., Nelissen, N. et al. Amyloid imaging in cognitively normal older adults: comparison between 18F-flutemetamol and 11C-Pittsburgh compound B. Eur J Nucl Med Mol Imaging 43, 142–151 (2016). https://doi.org/10.1007/s00259-015-3156-9

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  • DOI: https://doi.org/10.1007/s00259-015-3156-9

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