Faião-Flores Fernanda, Coelho Paulo Rogério Pinto, Arruda-Neto João Dias Toledo, Camillo Maria Aparecida Pires, Maria-Engler Silvya Stuchi, Rici Rose Eli Grassi, Sarkis Jorge Eduardo Souza, Maria Durvanei Augusto
Laboratory of Biochemistry and Biophysics, Butantan Institute, 1500 Vital Brasil Avenue, São Paulo, SP 05503-900, Brazil.
Radiat Environ Biophys. 2012 Aug;51(3):319-29. doi: 10.1007/s00411-012-0416-y. Epub 2012 Apr 11.
Information on (10)B distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The (10)B concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the (10)B concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of (10)B uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.
关于硼-10((^{10}B))在正常组织中的分布信息对于硼中子俘获疗法(BNCT)的进一步发展至关重要。本研究的目的是通过一种简单快速的比色法,研究B16F10小鼠黑色素瘤及正常组织中硼的体外和体内生物分布,该方法经高分辨率电感耦合等离子体质谱(HR-ICP-MS)验证。B16F10黑色素瘤细胞系的黑色素含量高于人类黑色素细胞,表明其摄取硼苯丙氨酸的潜力更大。在应用BNCT后的最初几分钟内,黑色素细胞的活力适度下降,75分钟后趋于稳定,而B16F10黑色素瘤在应用后150分钟时细胞内硼浓度最高,这表明黑色素瘤细胞与正常黑色素细胞的硼摄取情况不同。此外,此时黑色素瘤细胞中硼摄取的增加量比正常黑色素细胞高约1.6倍。荷B16F10黑色素瘤小鼠血液中的硼-10浓度在应用BNCT后90分钟内升高,120分钟后下降,并在240分钟前一直保持在较低水平。另一方面,肿瘤中的硼-10浓度从90分钟开始升高,应用后150分钟时达到最高,从而证实了体外实验结果。因此,目前关于正常细胞和肿瘤细胞摄取硼-10的体外和体内研究揭示了重要数据,这些数据可能使BNCT能够用作治疗黑色素瘤的方法,黑色素瘤是一种具有高死亡率的化疗耐药性癌症。