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Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model
Title: | Increased intratumoral fluorothymidine uptake levels following multikinase inhibitor sorafenib treatment in a human renal cell carcinoma xenograft model |
Authors: | Murakami, Masahiro Browse this author | Zhao, Songji Browse this author →KAKEN DB | Zhao, Yan Browse this author | Yu, Wenwen Browse this author | Fatema, Chowdhury Nusrat Browse this author | Nishijima, Ken-Ichi Browse this author | Yamasaki, Masahiro Browse this author →KAKEN DB | Takiguchi, Mitsuyoshi Browse this author →KAKEN DB | Tamaki, Nagara Browse this author →KAKEN DB | Kuge, Yuji Browse this author →KAKEN DB |
Keywords: | fluorothymidine | positron emission tomography | tumor proliferation | anti-angiogenic therapy | Ki-67 labeling index |
Issue Date: | Sep-2013 |
Publisher: | Spandidos Publ Ltd |
Journal Title: | Oncology Letters |
Volume: | 6 |
Issue: | 3 |
Start Page: | 667 |
End Page: | 672 |
Publisher DOI: | 10.3892/ol.2013.1459 |
Abstract: | An early identification of the tumor response to sorafenib treatment is indispensable for selecting optimal personalized treatment strategies. However, at present, no reliable predictors are clinically available. F-18-fluorothymidine (F-18-FLT) positron emission tomography (PET) is used to assess tumor proliferation, since the FLT uptake level reflects thymidine kinase-1 (TK-1) activity. Thus, the present study determined whether FLT was able to evaluate the early tumor response to sorafenib treatment in a human renal cell carcinoma (RCC; A498) xenograft in comparison with the tumor proliferation marker, Ki-67. Mice bearing A498 tumors were assigned to the control and sorafenib-treated groups and the tumor volume was measured every day. [Methyl-3H(N)]-3'-fluoro-3'-deoxythymidine (H-3-FLT) was injected 2 h prior to the sacrifice of the mice on days three and seven following the treatment. H-3-FLT autoradiography (ARG) and Ki-67 immunohistochemistry (IHC) were performed using adjacent tumor sections. In the visual assessment, the intratumoral H-3-FLT uptake level diffusely increased following the treatment, while no significant changes were observed in Ki-67 IHC. The intratumoral H-3-FLT uptake levels significantly increased by 2.7- and 2.6-fold on days three and seven following the treatment, while the tumor volume and Ki-67 index did not significantly change. Thus, an increased FLT uptake level was demonstrated following the treatment, which may indicate the suppression of thymidylate synthase (TS) and the compensatory upregulation of TK-1 activity by sorafenib. |
Type: | article |
URI: | http://hdl.handle.net/2115/54744 |
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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