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Monitoring tumor proliferative response to radiotherapy using F-18-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

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Title: Monitoring tumor proliferative response to radiotherapy using F-18-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67
Authors: Fatema, Chowdhury Nusrat Browse this author
Zhao, Songji Browse this author →KAKEN DB
Zhao, Yan Browse this author
Murakami, Masahiro Browse this author
Yu, Wenwen Browse this author
Nishijima, Ken-ichi Browse this author
Tamaki, Nagara Browse this author →KAKEN DB
Kitagawa, Yoshimasa Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Keywords: F-18-fluorothymidine
Radiotherapy
Tumor proliferation
Ki-67 labeling index
Head and neck cancer xenograft
Issue Date: May-2013
Publisher: Springer
Journal Title: Annals of Nuclear Medicine
Volume: 27
Issue: 4
Start Page: 355
End Page: 362
Publisher DOI: 10.1007/s12149-013-0693-9
PMID: 23417197
Abstract: Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using F-18-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT. FaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. H-3-FLT was injected intravenously 2 h before killing. Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment. Intratumoral H-3-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed. In radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral H-3-FLT level diffusely decreased 6 h after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral H-3-FLT level markedly decreased to 45 and 40 % of the control, respectively (P < 0.0001 vs control), and then gradually increased with time. In each radiation-treated group, the H-3-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral H-3-FLT levels in both treated groups were 68 and 60 % at 24 h (P < 0.001), 71 and 77 % at 48 h (P < 0.001), and 83 and 81 % on day 7 (P = NS) compared with the control group. Intratumoral FLT uptake level markedly decreased at 6 h and then gradually increased with time. Sequential evaluation of intratumoral proliferative activity using FLT can be beneficial for determining the optimal timing of and dose in repetitive irradiation of head and neck cancer.
Rights: The final publication is available at link.springer.com
Type: article (author version)
URI: http://hdl.handle.net/2115/55275
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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