当前位置: X-MOL 学术Int. J. Radiat. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Accelerator-based boron neutron capture therapy for malignant glioma: a pilot neutron irradiation study using boron phenylalanine, sodium borocaptate and liposomal borocaptate with a heterotopic U87 glioblastoma model in SCID mice.
International Journal of Radiation Biology ( IF 2.6 ) Pub Date : 2020-05-12 , DOI: 10.1080/09553002.2020.1761039
Evgenii Zavjalov 1, 2 , Alexander Zaboronok 1, 3 , Vladimir Kanygin 1 , Anna Kasatova 1, 4 , Aleksandr Kichigin 1 , Rinat Mukhamadiyarov 1, 5 , Ivan Razumov 1, 2 , Tatiana Sycheva 4 , Bryan J Mathis 3 , Sakura Eri B Maezono 6 , Akira Matsumura 3 , Sergey Taskaev 4, 7
Affiliation  

Purpose: To evaluate the efficacy of boron neutron capture therapy (BNCT) for a heterotopic U87 glioblastoma model in SCID mice using boron phenylalanine (BPA), sodium borocaptate (BSH) and liposomal BSH as boron compounds at a unique, accelerator-based neutron source.

Materials and methods: Glioblastoma models were obtained by subcutaneous implantation of U87 cells in the right thighs of SCID mice before administration of 350 mg/kg of BPA (BPA-group), 100 mg/kg of BSH (BSH-group) or 100 mg/kg of BSH in PEGylated liposomes (liposomal BSH-group) into the retroorbital sinus. Liposomes were prepared by reverse-phase evaporation. Neutron irradiation was carried out at a proton accelerator with a lithium target developed for BNCT at the Budker Institute of Nuclear Physics, Novosibirsk, Russian Federation. A proton beam current integral of 3 mA/h and energy of 2.05 MeV were used for neutron generation.

Results: Boron compound accumulation in tumor tissues at the beginning of irradiation was higher in the BPA group, followed by the Liposomal BSH and BSH groups. Tumor growth was significantly slower in all irradiated mice from the 7th day after BNCT compared to untreated controls (p < .05). Tumor growth in all treated groups showed no large variation, apart from the Irradiation only group and the BPA group on the 7th day after BNCT. The overall trend of tumor growth was clear and the differences between treatment groups became significant from the 50th day after BNCT. Tumor growth was significantly slower in the Liposomal BSH group compared to the Irradiation only group on the 50th (p = .012), 53rd (p = .005), and the 57th (p = .021) days after treatment. Tumor growth in the Liposomal BSH group was significantly different from that in the BPA group on the 53rd day after BNCT (p = .021) and in the BSH group on the 50th (p = .024), 53rd (p = .015), and 57th (p = .038) days after BNCT. Skin reactions in the form of erosions and ulcers in the tumor area developed in treated as well as untreated animals with further formation of fistulas and necrotic decay cavities in most irradiated mice.

Conclusions: We observed a tendency of BNCT at the accelerator-based neutron source to reduce or suspend the growth of human glioblastoma in immunodeficient animals. Liposomal BSH showed better long-term results compared to BPA and non-liposomal BSH. Further modifications in liposomal boron delivery are being studied to improve treatment outcomes.



中文翻译:

基于加速器的硼中子俘获治疗恶性神经胶质瘤:使用硼苯丙氨酸,硼captate钠和脂质体硼captate与异位U87胶质母细胞瘤模型在SCID小鼠中进行的中子辐射试验研究​​。

目的:评估硼中子俘获疗法(BNCT)对SCID小鼠异位U87胶质母细胞瘤模型的疗效,该研究使用硼苯丙氨酸(BPA),硼氢化钠(BSH)和脂质体BSH作为硼化合物在独特的基于促进剂的中子源。

材料和方法:胶质母细胞瘤模型是通过在将350 mg / kg的BPA(BPA组),100 mg / kg的BSH(BSH组)或100 mg的SCID小鼠的右大腿皮下植入U87细胞而获得的/ kg聚乙二醇化脂质体(脂质体BSH组)中的BSH进入眼眶后窦。通过反相蒸发制备脂质体。在俄罗斯联邦新西伯利亚的Budker核物理研究所,为BNCT开发的锂靶在质子加速器上进行了中子辐照。中子产生使用3 mA / h的质子束电流积分和2.05 MeV的能量。

结果: BPA组在放射开始时在肿瘤组织中的硼化合物积累较高,其次是脂质体BSH和BSH组。与未治疗的对照组相比,从BNCT术后第7天起,所有受辐照的小鼠的肿瘤生长明显减慢(p  <.05)。BNCT后第7天,除仅辐照组和BPA组外,所有治疗组的肿瘤生长均无明显变化。从BNCT后第50天开始,肿瘤生长的总体趋势是明确的,并且治疗组之间的差异变得明显。与仅在第50(p  = .012),第53(p  = .005)和第57(p = .021)。脂质体BSH组中肿瘤的生长是从在第53天的BPA组显著不同后BNCT(p  = 0.021)和BSH组中的第50(p  = 0.024),第53(p  = 0.015)以及 BNCT之后的第57天(p = .038)。在经过处理的动物和未经处理的动物中,皮肤区域均以糜烂和溃疡的形式出现皮肤反应,在大多数受辐照的小鼠中进一步形成瘘管和坏死性蛀牙。

结论:我们观察到在免疫缺陷动物中,基于加速器的中子源的BNCT有减少或中止人胶质母细胞瘤生长的趋势。与BPA和非脂质体BSH相比,脂质体BSH的长期效果更好。正在研究脂质体硼输送的进一步修饰以改善治疗效果。

更新日期:2020-07-07
down
wechat
bug