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用于治疗肺部肿瘤的硼中子俘获治疗(BNCT)的转化研究。

Translational boron neutron capture therapy (BNCT) studies for the treatment of tumors in lung.

机构信息

a Comisión Nacional de Energía Atómica , Buenos Aires, Argentina.

b Consejo Nacional de Investigaciones Científicas y Técnicas , Buenos Aires, Argentina.

出版信息

Int J Radiat Biol. 2019 May;95(5):646-654. doi: 10.1080/09553002.2019.1564080. Epub 2019 Feb 22.

DOI:10.1080/09553002.2019.1564080
PMID:30601686
Abstract

PURPOSE

Boron neutron capture therapy (BNCT) combines selective accumulation of B carriers in tumor tissue with subsequent neutron irradiation. BNCT has been proposed for the treatment of multiple, non-resectable, diffuse tumors in lung. The aim of the present study was to evaluate the therapeutic efficacy and toxicity of BNCT in an experimental model of lung metastases of colon carcinoma in BDIX rats and perform complementary survival studies.

MATERIALS AND METHODS

We evaluated tumor control and toxicity in lung 2 weeks post-BNCT at 2 dose levels, including 5 experimental groups per dose level: T0 (euthanized pre-treatment), Boronophenylalanine-BNCT (BPA-BNCT), BPA + Sodium decahydrodecaborate-BNCT ((BPA + GB-10)-BNCT), Beam only (BO) and Sham (no treatment, same manipulation). Tumor response was assessed employing macroscopic and microscopic end-points. An additional experiment was performed to evaluate survival and oxygen saturation in blood.

RESULTS AND CONCLUSIONS

No dose-limiting signs of short/medium-term toxicity were observed in lung. All end-points revealed statistically significant BNCT-induced tumor control vs Sham at both dose levels. The survival experiment showed a statistically significant 45% increase in post-treatment survival time in the BNCT group (48 days) versus Sham (33 days). These data consistently revealed growth suppression of lung metastases by BNCT with no manifest lung toxicity. Highlights Boron Neutron Capture Therapy suppresses growth of experimental lung metastases No BNCT-induced short/medium-term toxicity in lung is associated with tumor control Boron Neutron Capture Therapy increased post-treatment survival time by 45.

摘要

目的

硼中子俘获疗法(BNCT)结合了肿瘤组织中 B 载体的选择性积累和随后的中子照射。BNCT 已被提议用于治疗多个不可切除的弥漫性肺肿瘤。本研究的目的是评估 BNCT 在 BDIX 大鼠结肠癌肺转移实验模型中的治疗效果和毒性,并进行补充生存研究。

材料和方法

我们在 BNCT 后 2 周评估了肺部的肿瘤控制和毒性,分为 2 个剂量水平,每个剂量水平包括 5 个实验组:T0(预处理前安乐死)、硼苯丙氨酸 BNCT(BPA-BNCT)、硼苯丙氨酸+十氢十硼酸钠 BNCT(BPA+GB-10-BNCT)、仅照射束(BO)和假手术(无治疗,相同操作)。采用宏观和微观终点评估肿瘤反应。进行了一项额外的实验来评估生存和血液中的氧饱和度。

结果和结论

在肺部未观察到短期/中期毒性的剂量限制迹象。在两个剂量水平下,所有终点均显示 BNCT 诱导的肿瘤控制与假手术相比具有统计学意义。生存实验显示,BNCT 组(48 天)的治疗后生存时间比假手术组(33 天)统计学上显著增加了 45%。这些数据一致表明 BNCT 抑制了肺转移瘤的生长,且没有明显的肺毒性。

重点 BNCT 抑制了实验性肺转移瘤的生长

BNCT 没有导致肺部短期/中期毒性,与肿瘤控制相关

BNCT 增加了治疗后的生存时间 45%

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