Studies about application of BNCT for human oral squamous cell carcinoma

本研究利用一例高级别口腔鳞状细胞癌(SCC)患者建立的FI细胞系和裸鼠FI癌实验模型获得以下结果：(1)BSH和BPA介导的BNCT对FI细胞均有较强的体外杀伤作用。尤其是BPA介导的BNCT的作用是BSH介导的BNCT的10-20倍。(2)腹腔注射后2小时(Ip)。在BPA 250 mg/kg中，BPA向肿瘤与正常组织(T/N)比为4.2：1(最大值)的FI癌组织提供了16ppm(最大值)的~(10)&GT；B。BSH给药剂量低(3-6ppm)，T/N值低，注射BSH 75 mg/kg后无高峰。(3)BPA作用2小时后各脏器或组织的B浓度依次为肿瘤(3.0)、舌(1.9)、颌下腺(1.3)、肺(1.5)、肝(1.4)，比较差异有统计学意义(P<0.05)。Bsh：…舌头(2.3)、肺(1.7)、肿瘤(1.5)、下颌骨(1.3)、颌下腺(1.3)、淋巴结(0.75)依次增多。这些数据表明，将BNCT应用于口腔癌时，BPA具有良好的T/N比的优势。基于这些数据，我们尝试将BNCT用于裸鼠FI移植瘤的实验模型。结果表明，京都大学研究堆(KUR)热中子束照射于250 mg/kg ip后2小时，持续70min(平均肿瘤热中子注量为7.5×10~(-1)~(-1)N/cm~2)。注射，可达到完全缓解。而BPA介导的BNCT或BSH介导的BNCT在其他条件下均不能，10~20GyGumma-射线对肿瘤生长的抑制作用不大。(4)BPA介导的BNCT还逆转了FI癌相关的肿瘤综合征，如恶病质和白细胞增多。(5)在面颊FI癌晚期头颈部恶性肿瘤模型小鼠中，BPA介导的BNCT与未治疗的对照组相比，肿瘤生长减少约3周，生存时间延长约7周。BNCT的副作用是一些长期存活的小鼠在照射后6个月左右出现白内障。这些数据表明，BNCT似乎对头颈部恶性肿瘤有效。较少

In this study we have got following results using FI cell line which have been established from a patient with high-grade oral squamous cell carcinoma (SCC) and using experimental model of nude mice bearing FI carcinoma (1)Both borocaptate sodium (BSH) mediated Boron Neutron Capture Therapy (BNCT) and boronophenylalanine (BPA) mediated BNCT had strong tumor-cell killing effects in the FI cell line in vitro. Especially the effect of BPA mediated BNCT was 10-20 times more than that of BSH mediated BNCT. (2)2-hour after intra-peritoneal injection (i.p.) of BPA 250mg/kg, BPA delivered 16 ppm (maximum) of ^<10>B to FI carcinoma tissue with tumor : normal tissue (T/N) ratio of 4.2 :1 (the maximum). BSH, however, delivered low dose (3-6 ppm) and low T/N ratio, which did not have a peak after injection of BSH 75mg/kg. (3)BPA brought ^<10>B concentration of each organ or tissue after 2-hour was tumor (3.0)> tongue (1.9) > submandibular gland (1.3) > lung (1.5) > liver (1.4), in turn (cf. BSH : … More tongue (2.3) > lung (1.7) > tumor (1.5) > mandible (1.3) > submandibular gland (1.3) > lymph nodes (0.75), in turn ). These data indicates that BPA have the advantage of good T/N ratio, when BNCT was applied to oral cancers. Based on these data, we tried BNCT for experimental model of nude mice bearing FI carcinoma. As a result of conditions that irradiation of thermal neutron beam of Kyoto University Research Reactor (KUR) lasted 70 min (an average fluence of thermal neutrons for tumor was 7.5x10^<12>n/cm^2) 2-hour after 250mg/kg i.p. injection, which could attain complete response. However other conditions of BPA mediated BNCT or BSH mediated BNCT could not 10-20 Gy of gumma-ray mediation had little effect on reduction of the tumor-growth. (4)And also BPA mediated BNCT reversed neoplastic syndrome associated with FI carcinoma such as cachexia and leukocytosis. (5)In the mice bearing FI carcinoma at cheek as advanced head and neck malignancies model also BPA mediated BNCT reduced tumor-growth about 3-week and lasting survival about 7-week, compared with those of untreated control mice. Side effects of BNCT were cataract about 6-month after the irradiation in some of long survival mice. These data indicates that BNCT seems to be effective on head and neck malignancies. Less