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Radiolabeled uracil derivative as a novel SPECT probe for thymidine phosphorylase : suppressed accumulation into tumor cells by target gene knockdown

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/50770

Title: Radiolabeled uracil derivative as a novel SPECT probe for thymidine phosphorylase : suppressed accumulation into tumor cells by target gene knockdown
Authors: Li, Hua Browse this author
Zhao, Songji Browse this author →KAKEN DB
Jin, Yongnan Browse this author
Nishijima, Ken-ichi Browse this author
Akizawa, Hiromichi Browse this author
Ohkura, Kazue Browse this author
Tamaki, Nagara Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Keywords: cellular uptake
5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil
small interfering RNA
thymidine phosphorylase
Issue Date: Dec-2011
Publisher: Lippincott Williams & Wilkins
Journal Title: Nuclear Medicine Communications
Volume: 32
Issue: 12
Start Page: 1211
End Page: 1215
Publisher DOI: 10.1097/MNM.0b013e32834b7ea7
PMID: 21934548
Abstract: Objectives: We developed a radiolabeled uracil derivative, 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU), as a novel SPECT probe for thymidine phosphorylase (TP). This radioiodinated IIMU has a high affinity for TP, and highly accumulates in the TP-expressing tumor cell line A431 (human epidermoid carcinoma). To evaluate the specificity of the cellular uptake of IIMU to TP expression, we examined the effects of TP knockdown on the uptake of 125I-labeled IIMU (125I-IIMU) in the tumor cells. Methods: TP-specific siRNA, glyceraldehyde 3-phosphate dehydrogenase (GAPDH)-specific siRNA (positive control), and negative control siRNA were transfected into A431 cells, respectively. Target-mRNA and protein expression levels of TP and GAPDH were examined 48 and 72 hours after transfection, respectively. The cellular uptake level of 125I-IIMU was also evaluated 72 hours after transfection. The results were compared after normalization with the corresponding negative controls. Results: After TP- and GAPDH-specific siRNA transfection, the expression levels of TP and GAPDH mRNA significantly decreased to 41% and 29%, respectively, as compared with the negative control (p < 0.001 for both). The expression levels of TP and GAPDH protein also significantly decreased to 34% and 30%, respectively (p < 0.001 for both). After TP-specific siRNA transfection, the cellular uptake level of 125I-IIMU significantly decreased to 66% (p < 0.001). In contrast, GAPDH siRNA transfection did not significantly affect the cellular uptake level of 125I-IIMU. Conclusion: siRNA-mediated TP knockdown significantly decreased the cellular uptake level of 125I-IIMU. This finding indicates that the uptake of IIMU in tumor cells is TP-specific and directly corresponds to TP expression levels.
Rights: This is a non-final version of an article published in final form in Nuclear Medicine Communications 32(12), December 2011, pp.1211–1215
Relation: http://journals.lww.com/nuclearmedicinecomm/pages/default.aspx
Type: article (author version)
URI: http://hdl.handle.net/2115/50770
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)

Submitter: 趙 松吉

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