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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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タイトル: Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice
著者: Zhao, Songji 著作を一覧する
Li, Hua 著作を一覧する
Nishijima, Ken-ichi 著作を一覧する
Zhao, Yan 著作を一覧する
Akizawa, Hiromichi 著作を一覧する
Shimizu, Yoichi 著作を一覧する
Ohkura, Kazue 著作を一覧する
Tamaki, Nagara 著作を一覧する
Kuge, Yuji 著作を一覧する
キーワード: Thymidine phosphorylase expression
5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU)
Liver
Small intestine
Normal mouse tissues
発行日: 2015年 8月
出版者: Springer
誌名: Annals of nuclear medicine
巻: 29
号: 7
開始ページ: 582
終了ページ: 587
出版社 DOI: 10.1007/s12149-015-0981-7
抄録: 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.
Rights: The final publication is available at link.springer.com
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/62585
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 趙 松吉

 

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