Analysis of Behavior of Boron Compounds for Neutron Capture Therapy in Animal Organism by Nuclear Magnetic Resonance

硼中子俘获疗法(BNCT)是一种利用核裂变能量，将中子照射到预先选择性蓄积的肿瘤部位，从而摧毁肿瘤的治疗方法。分裂反应是^&lt；10&gt；B+n-^7Li+a。目前，p-BPA被用于选择性地将^&lt；10&gt；B聚集到恶性黑色素瘤中。在黑色素瘤中，黑色素合成加剧，在黑色素合成有机体中，作为黑色素前体的DOPA、DHI、DHICA大量存在。通过我们对水溶液的^&lt；11&gt；B-核磁共振研究表明，p-BPA与这些黑色素前体形成了络合物，当这些络合物被氧化时，p-BPA被分解为硼酸和酪氨酸。在本研究中，以金黄地鼠黑色素瘤为研究对象，对含有黑色素前体的细胞器进行了分级，p-bpa为addi…研究了p-BPA与黑色素前体之间的相互作用。小颗粒组分(SGF)和大颗粒组分(LGF)分别是黑素前体丰富的小颗粒组分(SGF)和大颗粒组分(LGF)，前者含有丰富的黑色素前体，后者含有黑素前体和黑素小体的黑素聚合物。在这两个组分中都加入了p-BPA，并测量了^&lt；11&gt；B-核磁共振。在SGF-p-BPA体系中，混合2小时后出现信号。这一信号似乎源于p-BPA-黑色素前体复合体。随着时间的延长，信号逐渐增强，混合8h后，信号变为宽广信号。在LGFp-BPA系统中，没有观察到这种信号。在黑色素瘤荷瘤仓鼠体内，加入p-BPA-果糖复合体。在给药后2小时和10小时，对金黄地鼠黑色素瘤进行分离，并测定其核磁共振波谱。在所有样品中都没有观察到p-BPA-黑色素前体的峰，但在所有样品中都观察到了硼酸的峰。黑色素分为两种，即黑色素和真黑素。P-BPA抑制这两种黑色素的形成。P-BPA与单糖形成的络合物多于m-BPA。P-双酚A与多巴胺的络合物。较少

Boron Neutron Capture Therapy (BNCT) is the therapy which utilize the nuclear fission energy to destroy the cancer by irradiation of neutron to the cancer part, where ^<10>B is previously selectively accumulated. The fission reaction is that ^<10>B + n-^7Li + a. At present, p-Boronophenylalanine (p-BPA) is used to accumulate ^<10>B selectively into malignant melanoma. In melanoma melanin synthesis is accentuated, and in the melanin synthesis organism, DOPA, DHI, DHICA, which are melanin precursors, exist in large quantities. By our ^<11>B-NMR study of aqueous solutions, it has become apparent that p-BPA complexes with these melanin precersors, and when the complexes are oxidized p-BPA is decomposed into boric acid and tyrosine. We have considered that the complex formation and decomposition correspond to the ^<10>B accumulation and release mechanism respectively.In this study, using hamster melanoma, cell organelles which contain melanin precursors were fractionated, and p-BPA was addi … More ng to each fractions, and the interactions between p-BPA and melanin precursors were investigated. Two kinds of fractions were prepared, that is, the small granule fractions(SGF), which contain many coated vesicles (CV) where melanin precursors are abundant and the large granule fractions(LGF), which contain premelanosome and melanosome, in both premelanosome and melanosome melanin polymers are abundant. Into the both fractions p-BPA was added and ^<11>B-NMR were measured. In SGF-p-BPA system, two hours after the mixing, a signal was appeared. The signal seems to be due to the p-BPA-melanin precursors complex. The signal increased with time and 8 hours after the mixing, the signal became a broad signal. In LGF p-BPA system, such signal was not observed.Into the melanoma bearing hamsters p-BPA-fructose complex was administrated. At 2 and 10 hours after administrations, melanoma of hamsters were fractionated, and ^<11>B-NMR was measured. The peak of p-BPA-melanin precursors was not observed in any samples, but the peak of boric acid was observed in all samples.By ^<11>B-NMR measurements, the following results were obtained. Melanin is divided into two types, i. e., pheomelanin and eumelanin. p-BPA inhibits both melanin formations. p-BPA more complexes with monosaccharides than m-BPA. p-BPA complexes with dopamine. Less