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Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice
| Title: | Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice |
| Authors: | Zhao, Songji Browse this author →KAKEN DB | | Li, Hua Browse this author | | Nishijima, Ken-ichi Browse this author | | Zhao, Yan Browse this author | | Akizawa, Hiromichi Browse this author →KAKEN DB | | Shimizu, Yoichi Browse this author →KAKEN DB | | Ohkura, Kazue Browse this author →KAKEN DB | | Tamaki, Nagara Browse this author →KAKEN DB | | Kuge, Yuji Browse this author →KAKEN DB |
| Keywords: | Thymidine phosphorylase expression | | 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU) | | Liver | | Small intestine | | Normal mouse tissues |
| Issue Date: | Aug-2015 |
| Publisher: | Springer |
| Journal Title: | Annals of nuclear medicine |
| Volume: | 29 |
| Issue: | 7 |
| Start Page: | 582 |
| End Page: | 587 |
| Publisher DOI: | 10.1007/s12149-015-0981-7 |
| PMID: | 25976738 |
| 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. |
| Rights: | The final publication is available at link.springer.com |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/62585 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 趙 松吉
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