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PET Imaging Analysis of Vitamin B1 Kinetics with [11C]Thiamine and its Derivative [11C]Thiamine Tetrahydrofurfuryl Disulfide in Rats

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Abstract

Purpose

Thiamine is an essential component of glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is better absorbed than readily-available water-soluble thiamine salts because it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions have not yet been clarified. C-11-labeled thiamine and TTFD were recently synthesized by our group. In this study, to clarify the differences in pharmacokinetics and metabolism of these probes, a quantitative PET imaging study and radiometabolite analysis of C-11-labeled thiamine and TTFD were performed in the rat heart.

Procedures

Positron emission tomography (PET) imaging with [11C]thiamine and [11C]TTFD was performed in normal rats to determine the pharmacokinetics of these probes, and the radiometabolites of both probes from the blood and heart tissue were analyzed by thin-layer chromatography.

Results

Accumulation of [11C]TTFD was significantly higher than that of [11C]thiamine in the rat heart. Moreover, as a result of the radiometabolite analysis of heart tissue at 15 min after the injection of [11C]TTFD, thiamine pyrophosphate, which serves as a cofactor for the enzymes involved in glucose metabolism, was found as the major radiometabolite and at a significantly higher level than in the [11C]thiamine-injected group.

Conclusions

PET imaging techniques for visualizing the kinetics and metabolism of thiamine using [11C]thiamine and [11C]TTFD were developed in this study. Consequently, noninvasive PET imaging for the pathophysiology of thiamine-related cardiac function may provide novel information about heart failure and related disorders.

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Acknowledgements

The authors would like to thank Mr. M. Kurahashi (Sumitomo Heavy Industry Accelerator Service Ltd.) for operating the cyclotron.

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Correspondence to Yasuyoshi Watanabe.

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All experimental protocols were approved by the Animal Care and Use Committee of RIKEN Kobe Institute and were performed in accordance with the National Institutes of Health Principles of Laboratory Animal Care. All applicable institutional and/or national guidelines for the care and use of animals were followed.

Conflict of Interest

This work was supported in part by an extramural research grant from Takeda Pharmaceutical Company Limited (Tokyo, Japan) to Yasuyoshi Watanabe. Yukihiro Nomura, Takahito Kitayoshi, Kouji Akimoto, and Shinji Nomura were employees of Takeda Pharmaceutical Company Limited. Other authors declare that there are no conflicts of interest.

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Nozaki, S., Mawatari, A., Nakatani, Y. et al. PET Imaging Analysis of Vitamin B1 Kinetics with [11C]Thiamine and its Derivative [11C]Thiamine Tetrahydrofurfuryl Disulfide in Rats. Mol Imaging Biol 20, 1001–1007 (2018). https://doi.org/10.1007/s11307-018-1186-y

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  • DOI: https://doi.org/10.1007/s11307-018-1186-y

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