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Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas
https://kagawa-u.repo.nii.ac.jp/records/207
https://kagawa-u.repo.nii.ac.jp/records/2073247d509-56dd-4633-89d8-ec3533772944
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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公開日 | 2014-03-24 | |||||||||||||
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タイトル | Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas | |||||||||||||
言語 | en | |||||||||||||
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言語 | eng | |||||||||||||
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資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||||
資源タイプ | doctoral thesis | |||||||||||||
著者 |
四宮, あや
× 四宮, あや
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内容記述タイプ | Abstract | |||||||||||||
内容記述 | Purpose The thymidine analog 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) has been developed as a positron emission tomography (PET) tracer to assess the proliferation activity of tumors in vivo. The present study investigated the relationship between the kinetic parameters of 18F-FLT in vivo and thymidine kinase-1 (TK-1) expression and cell proliferation rate in vitro, and blood–brain barrier (BBB) breakdown in human brain gliomas. |
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言語 | en | |||||||||||||
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内容記述タイプ | Abstract | |||||||||||||
内容記述 | Methods A total of 21 patients with newly diagnosed gliomas were examined by 18F-FLT PET kinetic analysis. Maximum standardized uptake value (SUVmax) and tumor-to-normal (T/N) ratio of 18F-FLT in the tumor and 18F-FLT kinetic parameters in the corresponding contralateral region were determined. The expression levels of TK-1 protein and mRNA were determined by immunohistochemistry (IHC) and real-time polymerase chain reaction (PCR), respectively, using surgical specimens. The cell proliferation rate of the tumor was determined in terms of the Ki-67 labeling index. BBB breakdown was evaluated on MR images with contrast enhancement. |
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言語 | en | |||||||||||||
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内容記述タイプ | Abstract | |||||||||||||
内容記述 | Results 18F-FLT SUVmax and T/N ratio were significantly correlated with the influx rate constant (K 1; P = 0.001 and P < 0.001, respectively), but not with the phosphorylation rate constant (k 3). IHC and real-time PCR studies demonstrated a significant correlation between K 1 and TK-1 mRNA expression (P = 0.001), but not between k 3 and TK-1 protein and mRNA expression. Linear regression analysis revealed a significant correlation between K 1 and the Ki-67 index (P = 0.003), but not between k 3 and the Ki-67 index. TK-1 mRNA expression was significantly correlated with the Ki-67 index (P = 0.009). 18F-FLT SUVmax and T/N ratio were significantly correlated with BBB breakdown evaluated by contrast enhancement in MR images (P = 0.003 and P = 0.011, respectively). |
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言語 | en | |||||||||||||
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内容記述タイプ | Abstract | |||||||||||||
内容記述 | Conclusion These results indicate that 18F-FLT uptake in the tumor is significantly related to transport through the disrupted BBB, but not through phosphorylation activity. Although the tissue TK-1 expression reflects tumor proliferation activity, the phosphorylation rate constant k 3 determined by 18F-FLT PET kinetic analysis does not accurately reflect TK-1 expression in the tissue and should not be used as a surrogate biomarker of cell proliferation activity in human brain gliomas. |
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言語 | en | |||||||||||||
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言語 | ja | |||||||||||||
学位名 | 博士(医学) | |||||||||||||
学位授与機関 | ||||||||||||||
識別子Scheme | kakenhi | |||||||||||||
識別子 | 16201 | |||||||||||||
言語 | ja | |||||||||||||
機関名 | 香川大学 | |||||||||||||
言語 | en | |||||||||||||
機関名 | Kagawa University | |||||||||||||
学位授与年月日 | ||||||||||||||
学位授与年月日 | 2014-03-24 | |||||||||||||
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学位授与番号 | 甲第592号 | |||||||||||||
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識別子タイプ | PMID | |||||||||||||
関連識別子 | 23229746 | |||||||||||||
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関連タイプ | isVersionOf | |||||||||||||
識別子タイプ | DOI | |||||||||||||
関連識別子 | https://doi.org/10.1007/s00259-012-2275-9 | |||||||||||||
KEID | ||||||||||||||
27475 |