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

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

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2211-2218
ページ数8
ジャーナルEuropean journal of nuclear medicine and molecular imaging
43
12
DOI
出版ステータスPublished - 2016 11 1

ASJC Scopus subject areas

  • 放射線学、核医学およびイメージング

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