Establishment of Boron Neutron Capture Therapy for Primary and Metastatic Melanoma Using Atomic Reactor and Accelerator

目前，硼中子俘获疗法（BNCT）很难治疗黑色素瘤患者，因为可用于医疗用途的机器时间非常有限。由于难以建造用于医疗用途的新型原子反应堆，我们研究了一种基于加速器的BNCT设施的概念设计。我们成功地设计了一个以Li为目标材料的初步加速器，其束流功率为65-150 kW，束流电流为20 mA (2.5 MeV)，束流电流为10 mA （10 MeV入射质子能量），可以在60 min内为BNCT产生足够的热中子和超热中子通量。通过转染酪氨酸酶基因或酪氨酸酶相关蛋白-2 （TRP-2）基因，在黑色素产量较高的细胞中，B-BPA的摄取增加。在体内将TRP-2基因转染黑色素瘤细胞的技术改进仍有待进一步研究。热辐射和低温辐射联合治疗距离皮肤表面4和5厘米的深部黑色素瘤是有效的。23例原发或转移性黑色素瘤患者接受^<10>B- bpa （85 mg/l kg或170 mg/kg静脉滴注）治疗后，经手术或BNCT行肿瘤、血液及正常皮肤组织中^<10>B含量测定，发现皮肤/血液^<10>B比值在1.2和1.5之间，肿瘤/血液^<10>B比值在给药结束后6h内也在3.0和4.0之间。此外，通过正电子发射断层扫描测量的^<18 b> f标记的^<10>B- bpa在黑色素瘤转移到大脑中的动力学证明是有效的估计黑色素瘤组织中^<10>B含量。这些结果强烈表明，使用^<10>B-BPA治疗黑色素瘤的BNCT已得到显著改善，并已成为黑色素瘤治疗中更有效的治疗方式，有助于提高黑色素瘤患者的生活质量。

It is difficult at present to treat melanoma patients by boron neutron capture therapy (BNCT), since machine time available for medical use is extremely limited.Due to difficulty of constucting a new atomic reactor for medical use, we investigated a conceptual design for an accelerator-based BNCT facility.We successfully designed a preliminary accelerator using Li as the target material, having beam power of 65-150 kW and beam current of 20 mA in 2.5 MeV or 10 mA in 10 MeV incident proton energy respectively which can produce enough thermal and epithermal neutron fluence for BNCT within 60 min.^<10>B-BPA uptake increased in cells having higher melanin production by transfection of the tyrosinase gene, or the tyrosinase related protein-2 (TRP-2) gene. Technical improvements for transfecting the TRP-2 gene into melanoma cells in vivo remains to be studied further.Combined thermal and epithermal radiation was proven to be effective in treating deeply-seated melanoma at 4 and 5 cm from the skin surface. By measuring ^<10>B content in tumor, blood and normal skin tissues of 23 patients with primary or metastatic melanoma who were operated on surgically or who underwent BNCT after receiving ^<10>B-BPA (85 mg/l kg or 170 mg/kg intravenous drip), the skin/blood ^<10>B ratio was found to be in the range of 1.2 and 1.5, and the tumor/blood ^<10>B ratio was also in the range of 3.0 and 4.0 within 6h after the end of administration. Further, kinetics of ^<18>F-labelled ^<10>B-BPA in melanoma metastasized into brain measured by positron emission tomography proved to be effective in estimating the ^<10>B content in melanoma tissue.These results strongly indicate that BNCT for melanoma using ^<10>B-BPA has been significantly improved and has become a more efficient therapeutic modality for melanoma treatments, contributing to a better quality of life for melanoma subjects.