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Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice

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Abstract

Objective

Thymidine phosphorylase (TP) is a key enzyme in the pyrimidine nucleoside salvage pathway and its expression is upregulated in a wide variety of solid tumors. In mice, we previously observed high and specific accumulation levels of our TP imaging probe, radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU) not only in high-TP-expressing tumors, but also in the liver and small intestine. To clarify the reason for the high accumulation levels of radioiodinated IIMU in the liver and small intestine, we investigated the expression levels of TP in mice in comparison with the biodistribution of radioiodinated IIMU (123I-IIMU).

Methods

BALB/cCrSlc mice were injected with 123I-IIMU, and the radioactivity levels [%ID/g (normalized to a mouse of 25 g body weight)] in the tissues of interest were determined 0.5, 1, 3 and 24 h after the injection (n = 5, each time point). To determine the expression levels of TP, BALB/cCrSlc and ddy mice (n = 3/each strain) were euthanized, and the heart, liver, lung, spleen, kidney, stomach, small intestine, large intestine and brain were collected. The mRNA and protein expression levels of TP in these organs were examined by quantitative reverse transcription-polymerase chain reaction and western blot analyses, respectively.

Results

In BALB/cCrSlc mice administered 123I-IIMU, markedly high radioactivity levels were observed in the liver [1.568 ± 0.237 (%ID/g)] and small intestine [0.506 ± 0.082 (%ID/g)], whereas those in the other tissues were fairly low [<0.010 ± 0.003 (%ID/g)] 30 min after the injection. The highest expression levels of TP mRNA were also observed in the liver and small intestine among the tissues tested. Immunoblotting showed intense immunoreactive bands of the TP protein for the liver and small intestine, whereas no notable bands were detected for other tissues. Similar expression profiles of TP mRNA and protein were observed in ddy mice.

Conclusion

We confirmed TP expression in various tissues of mice at the mRNA and protein levels: high TP expression levels were observed in the liver and small intestine. These high TP expression levels are consistent with the high accumulation levels of 123I-IIMU in these tissues. Our results may provide important information about the physiological accumulation of 123I-IIMU, which may be useful for the clinical diagnostic imaging of TP.

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Acknowledgments

This study was supported (in part) by the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program, Ministry of Education, Culture, Sports, Science and Technology, Japan. We also thank Nihon Medi-Physics Co., Ltd., for providing 123I-NaI.

Conflict of interest

We declare no other potential conflict of interest relevant to this article.

Author information

Authors and Affiliations

  1. Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Songji Zhao & Hua Li

  2. Department of Molecular Imaging, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Songji Zhao

  3. Department of Integrated Molecular Imaging, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Ken-ichi Nishijima, Yoichi Shimizu & Yuji Kuge

  4. Central Institute of Isotope Science, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-0815, Japan

    Ken-ichi Nishijima, Yoichi Shimizu & Yuji Kuge

  5. Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Yan Zhao & Nagara Tamaki

  6. Laboratory of Physical Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo, 194-8543, Japan

    Hiromichi Akizawa

  7. Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan

    Kazue Ohkura

Authors
  1. Songji Zhao
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  2. Hua Li
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  3. Ken-ichi Nishijima
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  4. Yan Zhao
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  5. Hiromichi Akizawa
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  6. Yoichi Shimizu
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  7. Kazue Ohkura
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  8. Nagara Tamaki
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  9. Yuji Kuge
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Corresponding author

Correspondence to Songji Zhao.

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Zhao, S., Li, H., Nishijima, Ki. et al. Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice. Ann Nucl Med 29, 582–587 (2015). https://doi.org/10.1007/s12149-015-0981-7

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  • DOI: https://doi.org/10.1007/s12149-015-0981-7

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