Experimental and Clinical Study on Boron Neutron Capture Therapy for Oral cancer

在临床研究中，我们根据诊断影像、18-BPA PET及临床表现评价BNCT的治疗效果。MRI结果显示t2加权图像信号强度降低，对比图像信号增强效果降低，肿瘤缩小。BNCT检查发现口腔黏膜炎，轻微不适，脱发，但治疗后无严重副作用，显示治疗效果良好。基础研究采用口腔鳞状细胞癌SAS和OSC-19细胞株检测转铁蛋白受体表达，结果显示转铁蛋白受体在SAS细胞表面表达。为了提高细胞对10B的摄取，我们制备了脂质体包埋的BSH （liposome-BSH）、脂质体包埋聚乙二醇修饰的BSH （PEG-liposome-BSH）和转铁蛋白结合的PEG-liposome-BSH (tgf -PEG-liposome-BSH)，并观察了癌细胞对10B摄取的差异。与其他化合物相比，tf - peg -脂质体显著增加细胞摄取。至于细胞内浓度的维持，也证明了tf - peg -脂质体- bsh在去除硼化合物后保持的时间比其他的更长。相反，过量的TF抑制了SAS细胞对TF- peg -脂质体- bsh的摄取。在对荷瘤小鼠的实验中，证实了该化合物增加了对肿瘤的10B摄取。我们的研究结果表明，TF在肿瘤细胞中过度表达，对增加肿瘤细胞对10B的摄取量和维持其浓度具有有益的作用，提示TF可能在未来的临床实践中作为载体有用。

For the clinical study, the therapeutic effects of BNCT were evaluated on the basis of diagnostic imaging, as well as 18-BPA PET and clinical findings. MRI results revealed a reduction in signal intensity in T2-weighted images, while a reduction in the signal enhancing effect in the contrast images was observed in addition to tumor shrinkage. In a BNCT examination, oral mucositis, slight malaise, and hair loss were noted, however, there were no serious side effects following treatment, demonstrating a favorable therapeutic effect.For the basic study, transferrin receptor expression was examined using the oral squamous cell carcinoma cell lines SAS and OSC-19, and the results showed expression of the receptor on the surface of SAS cells. Further, to improve 10B uptake by the cells, we made preparations of BSH embedded in liposome (liposome-BSH), BSH embedded in liposome and modified with polyethylene glycol (PEG-liposome-BSH), and PEG-liposome-BSH bound with transferrin (TF-PEG-liposome-BSH), then examined the differences in uptake by the cancer cells. Cellular uptake was significantly increased with TF-PEG-liposome as compared to the other compounds. As for the maintenance of intracellular concentration, it was also demonstrated that TF-PEG-liposome-BSH remained longer than the others after the removal of the boron compound. In contrast, excessive TF inhibited the uptake of TF-PEG-liposome-BSH by SAS cells. In an experiment using tumor bearing mice, it was confirmed that 10B uptake to the tumors was increased with that compound.Our findings demonstrated that TF, which is excessively expressed in tumor cells, has beneficial effects to increase the amount of 10B uptake by tumor cells and maintain its concentration, suggesting that TF may be useful as a carrier in future clinical practice.