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European Journal of Nuclear Medicine and Molecular Imaging

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01-01-2013 | Original Article

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

Authors: Aya Shinomiya, Nobuyuki Kawai, Masaki Okada, Keisuke Miyake, Takehiro Nakamura, Yoshio Kushida, Reiji Haba, Nobuyuki Kudomi, Yuka Yamamoto, Masaaki Tokuda, Takashi Tamiya

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2013

Abstract

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.

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Title: Evaluation of 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) kinetics correlated with thymidine kinase-1 expression and cell proliferation in newly diagnosed gliomas
Authors: Aya Shinomiya
Nobuyuki Kawai
Masaki Okada
Keisuke Miyake
Takehiro Nakamura
Yoshio Kushida
Reiji Haba
Nobuyuki Kudomi
Yuka Yamamoto
Masaaki Tokuda
Takashi Tamiya
Publication date: 01-01-2013
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2013
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-012-2275-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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