2026-03-13T08:10:34Z https://kagawa-u.repo.nii.ac.jp/oai

oai:kagawa-u.repo.nii.ac.jp:00000207 2024-10-31T07:59:49Z 13:40

Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas Shinomiya, Aya 四宮, あや シノミヤ, アヤ 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. 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. 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). 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. eng doctoral thesis https://kagawa-u.repo.nii.ac.jp/records/207 https://doi.org/10.1007/s00259-012-2275-9 23229746 甲第592号 博士（医学） 2014-03-24 16201 香川大学 Kagawa University https://kagawa-u.repo.nii.ac.jp/record/207/files/Med_A592_abstract.pdf application/pdf 264.2 kB 2020-10-27 https://kagawa-u.repo.nii.ac.jp/record/207/files/Med_A592_result.pdf application/pdf 369.2 kB 2020-10-27