title: Comparison of New Tau PET-Tracer Candidates With [18F]T808 and [18F]T807.
abstract: Early clinical results of two tau tracers, [(18)F]T808 and [(18)F]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 vivoradiometabolite analysis using high-performance liquid chromatography showed the presence of polar radiometabolites in plasma and brain. No specific binding of [(18)F]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 [(18)F]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.
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Lieven
authors.initials: L
authors.lastname: Declercq
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Celen
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Joan
authors.initials: J
authors.lastname: Lecina
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Muneer
authors.initials: M
authors.lastname: Ahamed
authors.affiliation: Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.affiliation: Janssen Research and Development, Neuroscience Discovery Biology, a division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Diederik
authors.initials: D
authors.lastname: Moechars
authors.affiliation: Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium.
authors.forename: Jesus
authors.initials: J
authors.lastname: Alcazar
authors.affiliation: Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ariza
authors.affiliation: Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: Fierens
authors.affiliation: Janssen Research and Development, Neuroscience Discovery Biology, a division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Astrid
authors.initials: A
authors.lastname: Bottelbergs
authors.affiliation: Janssen Research and Development, Neuroscience Discovery Biology, a division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mariën
authors.affiliation: Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium.
authors.forename: Ignacio Jose
authors.initials: IJ
authors.lastname: Andres
authors.affiliation: Nuclear Medicine & Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium guy.bormans@pharm.kuleuven.be.
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D001923:Brain Chemistry; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010949:Plasma / Q000737:chemistry; D049268:Positron-Emission Tomography; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001562:Benzimidazoles; D005462:Fluorine Radioisotopes; C054369:MAPT protein, human; D011743:Pyrimidines; D019275:Radiopharmaceuticals; C000588468:T808 compound; D016875:tau Proteins
keywords: Alzheimer; PET imaging; biomarker; molecular imaging of neurodegenerative diseases