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

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).

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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

Keywords

  • Neutron capture therapy
  • Gadolinium
  • Nanoparticles
  • Calcium phosphate