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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-11-2016 | Original Article

Characterization of the radiolabeled metabolite of tau PET tracer ¹⁸F-THK5351

Authors: Ryuichi Harada, Shozo Furumoto, Tetsuro Tago, Furukawa Katsutoshi, Aiko Ishiki, Naoki Tomita, Ren Iwata, Manabu Tashiro, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka Kudo, Nobuyuki Okamura

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2016

Abstract

Purpose

¹⁸F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of ¹⁸F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties.

Methods

Venous blood samples were collected from three human subjects after injection of ¹⁸F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood–brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples.

Results

About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of ¹⁸F-THK5351. The isolated radiometabolite of ¹⁸F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood–brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples.

Conclusions

These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images.

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Title: Characterization of the radiolabeled metabolite of tau PET tracer 18F-THK5351
Authors: Ryuichi Harada
Shozo Furumoto
Tetsuro Tago
Furukawa Katsutoshi
Aiko Ishiki
Naoki Tomita
Ren Iwata
Manabu Tashiro
Hiroyuki Arai
Kazuhiko Yanai
Yukitsuka Kudo
Nobuyuki Okamura
Publication date: 01-11-2016
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-016-3453-y

At a glance: The STEP trials

Springer Medicine

Characterization of the radiolabeled metabolite of tau PET tracer ¹⁸F-THK5351

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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