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

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Abstract

Objective

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 18F-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.

Methods

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. 3H-FLT was injected intravenously 2 h before killing. Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment. Intratumoral 3H-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed.

Results

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 3H-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 3H-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 3H-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral 3H-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.

Conclusion

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.

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Acknowledgments

This study was partially supported by the ‘Project for Developing Innovation Systems: Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program’ from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. This study was also partially supported by JSPS KAKENHI grant no. 23591732. The authors are grateful to the staff of the Department of Nuclear Medicine, Central Institute of Isotope Science and Department of Oral Diagnosis and Oral Medicine, Hokkaido University.

Conflict of interest

No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. Department of Oral Diagnosis and Oral Medicine, Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7, Kita-ku, Sapporo, 060-8586, Japan

    Chowdhury Nusrat Fatema, Wenwen Yu & Yoshimasa Kitagawa

  2. Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Chowdhury Nusrat Fatema, Songji Zhao, Yan Zhao, Masahiro Murakami, Wenwen Yu & Ken-ichi Nishijima

  3. Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan

    Yan Zhao & Nagara Tamaki

  4. Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, 060-0818, Japan

    Masahiro Murakami

  5. Central Institute of Isotope Science, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-0815, Japan

    Yuji Kuge

Authors
  1. Chowdhury Nusrat Fatema
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  2. Songji Zhao
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  3. Yan Zhao
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  8. Yoshimasa Kitagawa
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  9. Yuji Kuge
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Correspondence to Songji Zhao.

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Fatema, C.N., Zhao, S., Zhao, Y. et al. Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67. Ann Nucl Med 27, 355–362 (2013). https://doi.org/10.1007/s12149-013-0693-9

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  • DOI: https://doi.org/10.1007/s12149-013-0693-9

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