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）是利用核裂变能，通过中子照射到肿瘤部位，将^<10>B预先选择性积累，从而破坏肿瘤的治疗方法。裂变反应为^<10>B + n-^7Li + a。目前利用对硼苯丙氨酸（p-BPA）选择性地积累^<10>B进入恶性黑色素瘤。在黑色素瘤中，黑色素的合成被强化，在黑色素合成生物体中，多巴、DHI、DHICA等黑色素前体大量存在。通过我们对水溶液的B-NMR研究，很明显，对双酚a与这些黑色素前体配合物，当配合物被氧化时，对双酚a分解成硼酸和酪氨酸。我们认为复合体的形成和分解分别对应于^<10>B的富集和释放机制。本研究以仓鼠黑色素瘤为研究对象，对含有黑色素前体的细胞器进行分离，在各组分中加入p-BPA，研究p-BPA与黑色素前体的相互作用。制备了两种组分，即含有大量黑色素前体的包膜囊泡（CV）的小颗粒组分（SGF）和含有黑色素前体和黑色素小体的大颗粒组分（LGF），其中黑色素前体和黑色素小体的黑色素聚合物都丰富。在两个组分中加入p-BPA，并测量了^<11>的B-NMR。在SGF-p-BPA体系中，混合后2小时出现信号。这个信号似乎是由于p- bpa -黑色素前体复合物。信号随时间增加，混频8小时后信号变宽。在LGF - p-BPA体系中，没有观察到这种信号。给患黑色素瘤的仓鼠注射对双酚a -果糖复合物。在给药后2小时和10小时，对仓鼠黑色素瘤进行分离，并测量^<11>B-NMR。在所有样品中均未观察到对双酚a -黑色素前体的峰值，但在所有样品中均观察到硼酸的峰值。通过^<11>的B-NMR测量，得到了以下结果。黑色素分为两种，即黑色素和真黑色素。p-BPA抑制两种黑色素的形成。p-BPA与单糖的配合物比m-BPA更多。p-BPA与多巴胺的复合物。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