Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807

Lieven Declercq, Sophie Celen, Joan Lecina, Muneer Ahamed, Thomas Tousseyn, Diederik Moechars, Jesus Alcazar, Manuela Ariza, Katleen Fierens, Astrid Bottelbergs, Jonas Marien, Rik Vandenberghe, Ignacio Andres, Koen Van Laere, Alfons Verbruggen, Guy Bormans

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    Abstract

    Early clinical results of two tau tracers, [18F]T808 and [18F]T807, have recently been reported. In the present study, the biodistribution, radiometabolite quantification, and competition-binding studies were performed in order to acquire comparative preclinical data as well as to establish the value of T808 and T807 as benchmark compounds for assessment of binding affinities of eight new/other tau tracers. Biodistribution studies in mice showed high brain uptake and fast washout. In vivo radiometabolite analysis using high-performance liquid chromatography showed the presence of polar radiometabolites in plasma and brain. No specific binding of [18F]T808 was found in transgenic mice expressing mutant human P301L tau. In semiquantitative autoradiography studies on human Alzheimer disease slices, we observed more than 50% tau selective blocking of [18F]T808 in the presence of 1 μmol/L of the novel ligands. This study provides a straightforward comparison of the binding affinity and selectivity for tau of the reported radiolabeled tracers BF-158, BF-170, THK5105, lansoprazole, astemizole, and novel tau positron emission tomography ligands against T807 and T808. Therefore, these data are helpful to identify structural requirements for selective interaction with tau and to compare the performance of new highly selective and specific radiolabeled tau tracers.

    Original languageEnglish
    Pages (from-to)1-15
    Number of pages15
    JournalMolecular Imaging
    Volume15
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Alzheimer
    • Biomarker
    • Molecular imaging of neurodegenerative diseases
    • PET imaging

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