Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807
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...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2016-01-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012115624920 |
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| author | Lieven Declercq Pharmacist Sofie Celen PhD Joan Lecina PhD Muneer Ahamed PhD Thomas Tousseyn Prof, MD, PhD Diederik Moechars PhD Jesus Alcazar PhD Manuela Ariza PhD Katleen Fierens PhD Astrid Bottelbergs PhD Jonas Mariën PhD Rik Vandenberghe Prof, MD, PhD Ignacio Jose Andres PhD Koen Van Laere Prof, MD, PhD Alfons Verbruggen Prof, PhD Guy Bormans Prof, PhD |
| author_facet | Lieven Declercq Pharmacist Sofie Celen PhD Joan Lecina PhD Muneer Ahamed PhD Thomas Tousseyn Prof, MD, PhD Diederik Moechars PhD Jesus Alcazar PhD Manuela Ariza PhD Katleen Fierens PhD Astrid Bottelbergs PhD Jonas Mariën PhD Rik Vandenberghe Prof, MD, PhD Ignacio Jose Andres PhD Koen Van Laere Prof, MD, PhD Alfons Verbruggen Prof, PhD Guy Bormans Prof, PhD |
| author_sort | Lieven Declercq Pharmacist |
| collection | DOAJ |
| description | 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 vivo radiometabolite 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. |
| format | Article |
| id | doaj-art-614086a8936e4b7ebe4f365af2458065 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-614086a8936e4b7ebe4f365af24580652025-01-03T01:24:46ZengSAGE PublishingMolecular Imaging1536-01212016-01-011510.1177/153601211562492010.1177_1536012115624920Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807Lieven Declercq Pharmacist0Sofie Celen PhD1Joan Lecina PhD2Muneer Ahamed PhD3Thomas Tousseyn Prof, MD, PhD4Diederik Moechars PhD5Jesus Alcazar PhD6Manuela Ariza PhD7Katleen Fierens PhD8Astrid Bottelbergs PhD9Jonas Mariën PhD10Rik Vandenberghe Prof, MD, PhD11Ignacio Jose Andres PhD12Koen Van Laere Prof, MD, PhD13Alfons Verbruggen Prof, PhD14Guy Bormans Prof, PhD15 Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium Translational Cell and Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium Janssen Research and Development, Neuroscience Discovery Biology, a division of Janssen Pharmaceutica NV, Beerse, Belgium Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium Janssen Research and Development, Neuroscience Discovery Biology, a division of Janssen Pharmaceutica NV, Beerse, Belgium Janssen Research and Development, Neuroscience Discovery Biology, a division of Janssen Pharmaceutica NV, Beerse, Belgium Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium Janssen Research and Development, Discovery Sciences, a division of Janssen-Cilag NV, Toledo, Belgium Nuclear Medicine & Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, BelgiumEarly 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 vivo radiometabolite 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.https://doi.org/10.1177/1536012115624920 |
| spellingShingle | Lieven Declercq Pharmacist Sofie Celen PhD Joan Lecina PhD Muneer Ahamed PhD Thomas Tousseyn Prof, MD, PhD Diederik Moechars PhD Jesus Alcazar PhD Manuela Ariza PhD Katleen Fierens PhD Astrid Bottelbergs PhD Jonas Mariën PhD Rik Vandenberghe Prof, MD, PhD Ignacio Jose Andres PhD Koen Van Laere Prof, MD, PhD Alfons Verbruggen Prof, PhD Guy Bormans Prof, PhD Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807 Molecular Imaging |
| title | Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807 |
| title_full | Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807 |
| title_fullStr | Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807 |
| title_full_unstemmed | Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807 |
| title_short | Comparison of New Tau PET-Tracer Candidates With [F]T808 and [F]T807 |
| title_sort | comparison of new tau pet tracer candidates with f t808 and f t807 |
| url | https://doi.org/10.1177/1536012115624920 |
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