Radiolabeled uracil derivative as a novel SPECT probe for thymidine phosphorylase : suppressed accumulation into tumor cells by target gene knockdown
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概要
- 論文の詳細を見る
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.
- Lippincott Williams & Wilkinsの論文
著者
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Tamaki Nagara
台湾
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Nakata Tomoaki
Second Department Of Internal Medicine Sapporo Medicine University
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Tamaki Nagara
Hokkaido University School Of Medicine Department Of Tracer Kinetics And Department Of Nuclear Medic
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Kuge Yuji
Department Of Tracer Kinetics Hokkaido University School Of Medicine
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Kuge Y
Hokkaido Univ. Sapporo Jpn
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Zhao Songji
Department Of Nuclear Medicine Hokkaido University Graduate School Of Medicine
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Nishijima Kenichi
Department Of Molecular Imaging Hokkaido University Graduate School Of Medicine
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Kuge Yuji
Central Institute Of Isotope Science Hokkaido University
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Tamaki Nagara
Department Of Nuclear Medicine Hokkaido University School Of Medicine
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Nakata Tomoaki
Department Of Cardiology Sapporo Medical University School Of Medicine
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Tamaki Nagara
Hokkaido University Graduate School Of Medicine Department Of Nuclear Medicine
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