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硼中子俘获疗法对原发性和转移性黑色素瘤细胞系的生物学有效性评估。

Assessment of biological effectiveness of boron neutron capture therapy in primary and metastatic melanoma cell lines.

作者信息

Rossini Andrés E, Dagrosa Maria A, Portu Agustina, Saint Martin Giselle, Thorp Silvia, Casal Mariana, Navarro Aimé, Juvenal Guillermo J, Pisarev Mario A

机构信息

Nuclear Regulatory Authority (ARN) , Argentina.

出版信息

Int J Radiat Biol. 2015 Jan;91(1):81-9. doi: 10.3109/09553002.2014.942013. Epub 2014 Aug 11.

Abstract

PURPOSE

In order to optimize the effectiveness of Boron Neutron Capture Therapy (BNCT), Relative Biological Effectiveness (RBE) and Compound Biological Effectiveness (CBE) were determined in two human melanoma cell lines, M8 and Mel-J cells, using the amino acid p-boronophenylalanine (BPA) as boron carrier.

MATERIALS AND METHODS

The effects of BNCT on the primary amelanotic cell line M8 and on the metastatic pigmented melanoma cell line Mel-J were studied using colony formation assay. The RBE values were determined using both a gamma ray source, and the neutron beam from the Nuclear Reactor of the National Atomic Energy Commission (RA-3). For the determination of the RBE, cells were irradiated with increasing doses of both sources, between 1 and 8 Gy; and for the determination of CBE factors, the cells were pre-incubated with BPA before irradiation. Afterwards, the cell surviving fraction (SF) was determined for each treatment.

RESULTS

Marked differences were observed between both cell lines. Mel-J cells were more radioresistant than the M8 cell line. The clonogenic assays showed that for a SF of 1%, the RBE values were 1.3 for M8 cells and 1.5 for Mel-J cells. Similarly, the CBE values for a 1% SF were 2.1 for M8 and 3 for Mel-J cell lines. For the endpoint of 0.1% of SF the RBE values obtained were 1.2 for M8 and 1.4 for Mel-J cells. Finally, CBE values calculated for a 0.1% were 2 and 2.6 for M8 and Mel-J cell lines respectively. In order to estimate the uptake of the non-radioactive isotope Boron 10 ((10)B), a neutron induced autoradiographic technique was performed showing discrepancies in (10)B uptake between both cell lines.

CONCLUSIONS

These obtained in vitro results are the first effectiveness factors determined for human melanoma at the RA-3 nuclear reactor and show that BNCT dosimetry planning for patients could be successfully performed using these new factors.

摘要

目的

为优化硼中子俘获疗法(BNCT)的疗效,使用氨基酸对硼苯丙氨酸(BPA)作为硼载体,在两种人黑色素瘤细胞系M8和Mel-J细胞中测定相对生物效应(RBE)和复合生物效应(CBE)。

材料与方法

采用集落形成试验研究BNCT对原发性无黑色素细胞系M8和转移性色素性黑色素瘤细胞系Mel-J的影响。使用伽马射线源和国家原子能委员会核反应堆(RA-3)的中子束测定RBE值。为测定RBE,用两种源的递增剂量(1至8 Gy)照射细胞;为测定CBE因子,细胞在照射前用BPA预孵育。然后,测定每种处理的细胞存活分数(SF)。

结果

在两种细胞系之间观察到显著差异。Mel-J细胞比M8细胞系更具放射抗性。克隆形成试验表明,对于1%的SF,M8细胞的RBE值为1.3,Mel-J细胞为1.5。同样,对于1% SF的CBE值,M8细胞系为2.1,Mel-J细胞系为3。对于0.1% SF的终点,M8细胞获得的RBE值为1.2,Mel-J细胞为1.4。最后,对于0.1%计算的CBE值,M8和Mel-J细胞系分别为2和2.6。为估计非放射性同位素硼10(¹⁰B)的摄取,进行了中子诱导放射自显影技术,显示两种细胞系在¹⁰B摄取方面存在差异。

结论

这些体外获得的结果是在RA-3核反应堆针对人黑色素瘤确定的首批疗效因子,表明使用这些新因子可为患者成功进行BNCT剂量测定规划。

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