Assessment of biological effectiveness of boron neutron capture therapy in primary and metastatic melanoma cell lines
Assessment of biological effectiveness of boron neutron capture therapy in primary and metastatic melanoma cell lines
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DOI：
10.3109/09553002.2014.942013
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发表时间：
2015-01-01
影响因子：
2.6
通讯作者：
Pisarev, Mario A.
中科院分区：
文献类型：
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作者：
Rossini, Andres E.;Dagrosa, Maria A.;Pisarev, Mario A.
目的：为了优化硼中子捕获疗法（BNCT）的有效性，使用氨基酸对硼苯丙氨酸（BPA）作为硼载体，测定两种人黑色素瘤细胞系M8和Mel-J细胞的相对生物有效性（RBE）和复合生物有效性（CBE）。材料和方法：BNCT对原发性无色素细胞系M8和转移性色素性黑色素瘤的影响使用集落形成测定法研究细胞系Mel-J。 RBE 值是使用伽马射线源和国家原子能委员会核反应堆 (RA-3) 的中子束确定的。为了测定 RBE，用两种源的剂量逐渐增加（1 至 8 Gy）对细胞进行照射；为了测定 CBE 因子，在照射前将细胞与 BPA 一起预孵育。然后，确定每次处理的细胞存活分数（SF）。结果：两种细胞系之间观察到显着差异。 Mel-J 细胞比 M8 细胞系具有更强的抗辐射能力。克隆形成分析表明，对于 1% 的 SF，M8 细胞的 RBE 值为 1.3，Mel-J 细胞的 RBE 值为 1.5。同样，1% SF 的 CBE 值对于 M8 为 2.1，对于 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 细胞获得的 RBE 值为 1.4。最后，M8 和 Mel-J 细胞系按 0.1% 计算的 CBE 值分别为 2 和 2.6。为了估计非放射性同位素硼 10 (B-10) 的摄取，进行了中子诱导放射自显影技术，显示两种细胞系之间 B-10 摄取的差异。结论：这些体外结果是在 RA-3 核反应堆中确定的第一个针对人类黑色素瘤的有效因素，并表明使用这些新因素可以成功地为患者进行 BNCT 剂量测定计划。
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 (B-10), a neutron induced autoradiographic technique was performed showing discrepancies in B-10 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.