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In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent.

Methods

In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 1012 n/cm2. Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice.

Results

The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis.

Conclusion

The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.

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Funding

This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan (Nos. 25670571, and 24390311 to Hironobu Yanagie).

Author information

Authors and Affiliations

  1. Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Novriana Dewi, Hironobu Yanagie & Hiroyuki Takahashi

  2. Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion, 66-20 Horikawa-cho, Saiwai-ku, Kawasaki, 212-0013, Japan

    Peng Mi, Nobuhiro Nishiyama & Kazunori Kataoka

  3. Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8503, Japan

    Peng Mi & Nobuhiro Nishiyama

  4. Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Peng Mi & Kazunori Kataoka

  5. Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Hironobu Yanagie, Yuriko Sakurai & Hiroyuki Takahashi

  6. Department of Innovative Cancer Therapeutics: Alpha Particle and Immunotherapeutics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan

    Hironobu Yanagie

  7. Department of Human and Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Yasuyuki Morishita

  8. Department of Applied Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2 Sen-11 Inadacho, Obihiro, Hokkaido, 080-0834, Japan

    Masashi Yanagawa

  9. Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Takayuki Nakagawa

  10. Department of Humanities, Graduate School of Seisen University, 3-16-21 Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8642, Japan

    Atsuko Shinohara

  11. Department of Epidemiology and Environmental Health, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Takehisa Matsukawa & Kazuhito Yokoyama

  12. Department of Bioengineering, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Horacio Cabral

  13. Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan

    Minoru Suzuki, Yoshinori Sakurai, Hiroki Tanaka & Koji Ono

  14. Department of Materials Engineering, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Kazunori Kataoka

Authors
  1. Novriana Dewi
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  2. Peng Mi
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  3. Hironobu Yanagie
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  4. Yuriko Sakurai
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  5. Yasuyuki Morishita
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  6. Masashi Yanagawa
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  7. Takayuki Nakagawa
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  8. Atsuko Shinohara
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  9. Takehisa Matsukawa
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  10. Kazuhito Yokoyama
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  11. Horacio Cabral
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  12. Minoru Suzuki
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  13. Yoshinori Sakurai
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  14. Hiroki Tanaka
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  15. Koji Ono
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  16. Nobuhiro Nishiyama
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  17. Kazunori Kataoka
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  18. Hiroyuki Takahashi
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Corresponding author

Correspondence to Hironobu Yanagie.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The procedures for tumor implantation and killing of the animals were carried out following the policies of the Animal Ethics Committee of the University of Tokyo and in accordance with the Declaration of Helsinki.

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Dewi, N., Mi, P., Yanagie, H. et al. In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent. J Cancer Res Clin Oncol 142, 767–775 (2016). https://doi.org/10.1007/s00432-015-2085-0

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  • DOI: https://doi.org/10.1007/s00432-015-2085-0

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