量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Introduction: [11C]PBB3 is a clinically used positron emission tomography
(PET) probe for in vivo imaging of tau pathology in the brain. Our previous
study showed that [11C]PBB3 was rapidly decomposed to a polar
radiometabolite in the plasma of mice. For the pharmacokinetic evaluation
of [11C]PBB3 it is important to elucidate the characteristics of
radiometabolites. In this study, we identified the chemical structure of a
major radiometabolite of [11C]PBB3 and proposed the metabolic pathway of
[11C]PBB3.
Methods: Carrier-added [11C]PBB3 was injected into a mouse for in vivo
metabolite analysis. The chemical structure of a major radiometabolite was
identified using LC–MS. Mouse and human liver microsomes and liver S9
samples were incubated with [11C]PBB3 in vitro. In silico prediction
software was used to assist in the determination of the metabolite and
metabolic pathway of [11C]PBB3.
Results: In vivo analysis showed that the molecular weight of a major
radiometabolite of [11C]PBB3, which was called as [11C]M2, was m/z 390
[M+H+]. In vitro analysis assisted by in silico prediction showed that
[11C]M2, which was not generated by cytochrome P450 enzymes (CYPs),
was generated by sulfated conjugation mediated by a sulfotransferase.
Conclusion: The major radiometabolite, [11C]M2, was identified as a
sulfated conjugate of [11C]PBB3. [11C]PBB3 was metabolized mainly by a sulfotransferase and subsidiarily by CYPs.
Identification of a major radiometabolite of [11C]PBB3
