使用基于磷酸钙的纳米颗粒作为钆喷酸葡胺递送剂对中子俘获疗法有效性进行的体内评估。

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

作者信息

Dewi Novriana, Mi Peng, Yanagie Hironobu, Sakurai Yuriko, Morishita Yasuyuki, Yanagawa Masashi, Nakagawa Takayuki, Shinohara Atsuko, Matsukawa Takehisa, Yokoyama Kazuhito, Cabral Horacio, Suzuki Minoru, Sakurai Yoshinori, Tanaka Hiroki, Ono Koji, Nishiyama Nobuhiro, Kataoka Kazunori, Takahashi Hiroyuki

机构信息

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

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

出版信息

J Cancer Res Clin Oncol. 2016 Apr;142(4):767-75. doi: 10.1007/s00432-015-2085-0. Epub 2015 Dec 9.

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 × 10(12) n/cm(2). 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.

摘要

目的

当前临床研究工作的治疗方法能产生更直接的影响备受关注,通过开发一种非侵入性辐射剂量递增策略或许可以实现,而中子俘获疗法就是这样一种新方法。此外,考虑到钆所具有的若干优势,近期一些关于中子俘获疗法的研究聚焦于使用钆作为当前所用硼的替代物或补充物。因此,在本研究中,我们对掺入磷酸钙纳米颗粒中的钆基磁共振成像造影剂单次及多次注射作为中子俘获治疗剂进行了可行性评估。

方法

在京都大学研究反应堆研究所的核反应堆设施中,对荷有结肠癌Col - 26肿瘤的小鼠进行体内评估,平均中子注量为1.8×10¹² n/cm²。基于中子辐照后直至27天的肿瘤生长抑制情况评估抗肿瘤有效性,随后对肿瘤切片进行组织病理学分析。

结果

实验结果表明,预先注射掺入钆 - 二乙三胺五乙酸的磷酸钙基纳米颗粒的辐照小鼠的肿瘤生长受到抑制,与未治疗组相比最高可达四倍,组织病理学分析结果支持这一结论。

结论

在中子辐照后对荷瘤小鼠观察到的抗肿瘤有效性结果表明钆基中子俘获治疗具有潜在有效性。

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