Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27475
Title
Evaluation of 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas
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Description

Abstract
PURPOSE:

The thymidine analog 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-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 (18)F-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 (18)F-FLT PET kinetic analysis. Maximum standardized uptake value (SUVmax) and tumor-to-normal (T/N) ratio of (18)F-FLT in the tumor and (18)F-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:

(18)F-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). (18)F-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 (18)F-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 (18)F-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.

(医博甲592)

Author
著者 四宮 あや
著者(ヨミ) シノミヤ
著者(別表記) Shinomiya Aya
Publication Title
European Journal of Nuclear Medicine and Molecular Imaging
Publication Title Alternative
Eur J Nucl Med Mol Imaging.
Volume
40
Issue
2
Start Page
175
End Page
185
Publisher
European Association of Nuclear Medicine
Springer
Published Date
2012-11-15
ISSN
1619-7070
NCID
AA1161516X
PMID
23229746
DOI
10.1007/s00259-012-2275-9
Resource Type
Thesis or Dissertation
Language
eng
Resource URL
https://doi.org/10.1007/s00259-012-2275-9
Text Version
none
Grant ID
博甲第592号
Grant Date
2014-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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