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Alzheimer's Research & Therapy
Published in: Alzheimer's Research & Therapy 1/2018

Open Access 01-12-2018 | Research

In vivo quantification of neurofibrillary tangles with [18F]MK-6240

Authors: Tharick A. Pascoal, Monica Shin, Min Su Kang, Mira Chamoun, Daniel Chartrand, Sulantha Mathotaarachchi, Idriss Bennacef, Joseph Therriault, Kok Pin Ng, Robert Hopewell, Reda Bouhachi, Hung-Hsin Hsiao, Andrea L. Benedet, Jean-Paul Soucy, Gassan Massarweh, Serge Gauthier, Pedro Rosa-Neto

Published in: Alzheimer's Research & Therapy | Issue 1/2018

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Abstract

Background

Imaging agents capable of quantifying the brain’s tau aggregates will allow a more precise staging of Alzheimer’s disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau imaging agent [18F]MK-6240.

Methods

In vitro properties of [18F]MK-6240 were estimated with autoradiography in postmortem brain tissues of 14 subjects (seven AD patients and seven age-matched controls). In vivo quantification of [18F]MK-6240 binding was performed in 16 subjects (four AD patients, three mild cognitive impairment patients, six healthy elderly individuals, and three healthy young individuals) who underwent 180-min dynamic scans; six subjects had arterial sampling for metabolite correction. Simplified approaches for [18F]MK-6240 quantification were validated using full kinetic modeling with metabolite-corrected arterial input function. All participants also underwent amyloid-PET and structural magnetic resonance imaging.

Results

In vitro [18F]MK-6240 uptake was higher in AD patients than in age-matched controls in brain regions expected to contain tangles such as the hippocampus, whereas no difference was found in the cerebellar gray matter. In vivo, [18F]MK-6240 displayed favorable kinetics with rapid brain delivery and washout. The cerebellar gray matter had low binding across individuals, showing potential for use as a reference region. A reversible two-tissue compartment model well described the time–activity curves across individuals and brain regions. Distribution volume ratios using the plasma input and standardized uptake value ratios (SUVRs) calculated after the binding approached equilibrium (90 min) were correlated and higher in mild cognitive impairment or AD dementia patients than in controls. Reliability analysis revealed robust SUVRs calculated from 90 to 110 min, while earlier time points provided inaccurate estimates.

Conclusions

This evaluation shows an [18F]MK-6240 distribution in concordance with postmortem studies and that simplified quantitative approaches such as the SUVR offer valid estimates of neurofibrillary tangle load 90 min post injection. [18F]MK-6240 is a promising tau tracer with the potential to be applied in the disease diagnosis and assessment of therapeutic interventions.
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Metadata
Title
In vivo quantification of neurofibrillary tangles with [18F]MK-6240
Authors
Tharick A. Pascoal
Monica Shin
Min Su Kang
Mira Chamoun
Daniel Chartrand
Sulantha Mathotaarachchi
Idriss Bennacef
Joseph Therriault
Kok Pin Ng
Robert Hopewell
Reda Bouhachi
Hung-Hsin Hsiao
Andrea L. Benedet
Jean-Paul Soucy
Gassan Massarweh
Serge Gauthier
Pedro Rosa-Neto
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 1/2018
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/s13195-018-0402-y

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