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Early [18F]florbetaben and [11C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer’s disease

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

Abstract

Purpose

[18F]FDG is a commonly used neuronal injury biomarker for early and differential diagnosis of dementia. Typically, the blood supply to the brain is closely coupled to glucose consumption. Early uptake of the Aβ tracer [11C]PiB on PET images is mainly determined by cerebral blood flow and shows a high correlation with [18F]FDG uptake. Uptake data for 18F-labelled Aβ PET tracers are, however, scarce. We investigated the value of early PET images using the novel Aβ tracer [18F]FBB in the diagnosis of Alzhimers disease (AD).

Methods

This retrospective analysis included 22 patients with MCI or dementia who underwent dual time-point PET imaging with either [11C]PiB (11 patients) or [18F]FBB (11 patients) in routine clinical practice. Images were acquired 1 – 9 min after administration of both tracers and 40 – 70 min and 90 – 110 min after administration of [11C]PiB and [18F]FBB, respectively. The patients also underwent [18F]FDG brain PET imaging. PET data were analysed visually and semiquantitatively. Associations between early Aβ tracer uptake and dementia as well as brain atrophy were investigated.

Results

Regional visual scores of early Aβ tracer and [18F]FDG PET images were significantly correlated (Spearman’s ρ = 0.780, P < 0.001). Global brain visual analysis revealed identical results between early Aβ tracer and [18F]FDG PET images. In a VOI-based analysis, the early Aβ tracer data correlated significantly with the [18F]FDG data (r = 0.779, P < 0.001), but there were no differences between [18F]FBB and [11C]PiB. Cortical SUVRs in regions typically affected in AD on early Aβ tracer and [18F]FDG PET images were correlated with MMSE scores (ρ = 0.458, P = 0.032, and ρ = 0.456, P = 0.033, respectively). A voxel-wise group-based search for areas with relatively higher tracer uptake on early Aβ tracer PET images compared with [18F]FDG PET images revealed a small cluster in the midbrain/pons; no significant clusters were found for the opposite comparison.

Conclusion

Early [18F]FBB and [11C]PiB PET brain images are similar to [18F]FDG PET images in AD patients, and these tracers could potentially be used as biomarkers in place of [18F]FDG. Thus, Aβ tracer PET imaging has the potential to provide biomarker information on AD pathology and neuronal injury. The potential of this approach for supporting the diagnosis of AD needs to be confirmed in prospective studies in larger cohorts.

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Acknowledgments

We thank all patients who took part in this trial. We also acknowledge the excellent support of the cyclotron, radiochemistry, and PET teams of the University of Leipzig, Department of Nuclear Medicine. Special thanks to Martin Wehner for his support in preparing the PET data analysis.

Assistance with editing the manuscript was provided by Michelle Thorpe (Bioscript Medical, London, UK) and funded by Piramal Imaging S.A.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany

    Solveig Tiepolt, Swen Hesse, Marianne Patt, Julia Luthardt, Osama Sabri & Henryk Barthel

  2. Clinic for Cognitive Neurology & Max Planck Institute for Human Cognitive & Brain Sciences, University of Leipzig, Leipzig, Germany

    Matthias L. Schroeter

  3. Department of Neuroradiology, University of Leipzig, Leipzig, Germany

    Karl-Titus Hoffmann

  4. Department of Neurology, University of Leipzig, Leipzig, Germany

    David Weise

  5. Department of Psychiatry, University of Leipzig, Leipzig, Germany

    Hermann-Josef Gertz

  6. Integrated Research and Treatment Center (IFB) Adiposity Diseases, Leipzig, Germany

    Swen Hesse & Osama Sabri

Authors
  1. Solveig Tiepolt
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Corresponding author

Correspondence to Solveig Tiepolt.

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Conflicts of interest

H.B. and O.S. receive consultant or speaker honoraria from Piramal Imaging.

S.H. has received travel grants and honoraria from General Electric (GE) Healthcare and Bayer Schering Pharma. S.H. is in part funded by a grant from the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01E01001 (http://www.bmbf.de).

M.L.S. has been supported by LIFE – Leipzig Research Center for Civilization Diseases at the University. LIFE is funded by the European Union, by the European Regional Development Fund (ERFD) and by the Free State of Saxony within the framework of the Excellence Initiative. M.L.S. is also supported by the German Federal Ministry of Education and Research (BMBF; German FTLD consortium – grant no. FKZ 01GI1007A), and by the Parkinson’s Disease Foundation (grant no. PDF-IRG-1307).

M.P. received a speaker’s fee from Roche, holds patents in cooperation with Piramal and ABX and received research grants from Navidea and Piramal.

The other authors declare that they have no conflicts of interest.

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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Tiepolt, S., Hesse, S., Patt, M. et al. Early [18F]florbetaben and [11C]PiB PET images are a surrogate biomarker of neuronal injury in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 43, 1700–1709 (2016). https://doi.org/10.1007/s00259-016-3353-1

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  • DOI: https://doi.org/10.1007/s00259-016-3353-1

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