Identification of a major radiometabolite of [11C]PBB3

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.

書誌情報

Nuclear Medicine and Biology

巻 42, 号 12, p. 905-910, 発行日 2015-11

出版者

Elsevier

PubMed番号

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PMID

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2023-05-15 23:40:33.312541

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