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[18F]-AV-1451 tau PET imaging in Alzheimer’s disease and suspected non-AD tauopathies using a late acquisition time window

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Abstract

The utility of tau PET imaging in non-Alzheimer’s disease (AD) tauopathies like behavioural frontotemporal dementia (bvFTD), which is mainly underlain by TDP-43 or tau pathology, remains debated. We aim to test the hypothesis that [18F]-AV-1451 tau PET using later than usual acquisition times, which have previously been shown in AD to allow to get closer to tracer equilibrium between the reference region and high-binding structures, and could be better suited to the lower affinity of this tracer for the straight tau filaments present in non-AD tauopathies, would allow to detect cortical tau pathology in a fraction of bvFTD patients and in patients with non-fluent primary progressive aphasia (nfPPA, most often underlain by tau pathology). Sixteen AD patients, 11 controls, 7 bvFTD patients (including a carrier of a GRN mutation leading to TDP-43 pathology) and 2 nfPPA patients were included. We compared SUVr obtained at the usual early time window for [18F]-AV-1451 PET acquisition (ET: 80–100 min) to a later acquisition window (LT: 190–210 min) between groups. Compared with ET, [18F]-AV-1451 LT uptake in AD patients was significantly higher in the temporo-parietal cortex, and lower in subcortical regions. The LT window allowed to detect significantly increased tau binding in the frontal or temporal cortex in 3 bvFTD patients and in the 2 nfPPA patients that was not detectable with ET. The GRN mutation carrier showed no significant increase of tracer binding. [18F]-AV-1451 late acquisition window could allow cortical binding to abnormal tau deposits to be revealed in a subset of bvFTD patients, which may distinguish them from the TDP-43 subtype.

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Abbreviations

AD:

Alzheimer’s disease

bvFTD:

Behavioural frontotemporal dementia

nfPPA:

Non-fluent/agrammatic variant of primary progressive aphasia

PET:

Positron emission tomography

CDR:

Clinical dementia rating

GCI:

Global cortical index

MMSE:

Mini-mental state examination

PiB:

Pittsburgh compound B

SUVr:

Standard uptake value ratio

ET:

Early time window

LT:

Late time window

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Acknowledgements

The authors are grateful to the chemical/radiopharmaceutical and nursing staff of the Service Hospitalier Frederic Joliot for the synthesis of [11C]-PIB and [18F]-AV-1451 and patient management, respectively, the staff of the Centre de Neuroimagerie de Recherche (CENIR), Salpêtrière Hospital, for patient management during MRI acquisition.

We are also indebted to AVID Radiopharmaceuticals, Inc., for their support in supplying the AV- 1451 precursor and chemistry production advice.

Funding

This study was funded by the French Ministry of Health grant (PHRC-2013-0919), CEA, Fondation pour la recherche sur Alzheimer, Institut de recherche internationale Servier, France-Alzheimer.

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Authors and Affiliations

  1. Unit of Neurology of Memory and Language, Université Paris Descartes, Sorbonne Paris Cité, Centre Hospitalier Sainte Anne, 1 rue Cabanis, 75014, Paris, France

    Julien Lagarde, Pauline Olivieri & Marie Sarazin

  2. UMR 1023, IMIV, Service Hospitalier Frédéric Joliot, CEA, Inserm, Université Paris Sud, CNRS, Université Paris-Saclay, Orsay, France

    Julien Lagarde, Fabien Caillé, Philippe Gervais, Michel Bottlaender & Marie Sarazin

  3. Department of Neurology, Centre Hospitalier Sainte-Anne, Inserm U894, Université Paris Descartes, Paris, France

    Jean-Claude Baron

  4. UNIACT, Neurospin, CEA, 91191, Gif-sur-Yvette, France

    Michel Bottlaender

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  1. Julien Lagarde
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  2. Pauline Olivieri
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  3. Fabien Caillé
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  4. Philippe Gervais
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  5. Jean-Claude Baron
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  7. Marie Sarazin
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Correspondence to Marie Sarazin.

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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 Helsinki declaration and its later amendments or comparable ethical standards.

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

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Lagarde, J., Olivieri, P., Caillé, F. et al. [18F]-AV-1451 tau PET imaging in Alzheimer’s disease and suspected non-AD tauopathies using a late acquisition time window. J Neurol 266, 3087–3097 (2019). https://doi.org/10.1007/s00415-019-09530-7

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  • DOI: https://doi.org/10.1007/s00415-019-09530-7

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