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

核磁共振分析硼化合物在动物体内中子捕获治疗的行为

• 批准号: 12680507
• 负责人: YOSHINO Kazuo
• 金额: $ 2.5万
• 依托单位: Shinsyu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680507/
• 关键词: p-BPA; Melanoma; Boron Neutron Capture Therapy; Melanin; Melanin Precursor; DHI; DHICA; ^<11>B-NMR; 中性子捕捉療法(NCT); 悪性黒色腫; p-ボロノフェニルアラニン; ドーパミン; ノルエピネフリン; エピネフリン; 中性子補足療法(NCT); m-ボロノフェニルアラニン; ユウメラニン; フェオメラニン; メラニンモノマー; 5-S-システニルドーパ

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

硼中子俘获疗法（BNCT）是利用核裂变能，通过中子照射~（B）选择性蓄积的癌组织部位，从而达到破坏癌组织的目的<10>。裂变反应为^<10>B + n-^7 Li + a.目前，对-硼苯丙氨酸（p-BPA）被用于选择性地将^ B蓄积<10>到恶性黑素瘤中。在黑色素瘤中，黑色素合成被加强，并且在黑色素合成生物体中，作为黑色素前体的DOPA、DHI、DHICA大量存在。通过我们<11>对水溶液的1H-NMR研究，已经变得明显的是，p-BPA与这些黑色素前体络合，并且当络合物被氧化时，p-BPA分解成硼酸和酪氨酸。我们认为，复合物的形成和分解分别对应于β-<10>B的积累和释放机制。在本研究中，用仓鼠黑色素瘤，分离含有黑色素前体的细胞器，并加入p-BPA， ...更多信息 ng加入到各组分中，研究了对双酚A与黑色素前体的相互作用。制备了两种组分，即小颗粒组分（SGF）和大颗粒组分（LGF），小颗粒组分含有许多被膜囊泡（CV），其中黑色素前体丰富，大颗粒组分含有前黑素体和黑素体，前黑素体和黑素体中的黑色素聚合物丰富。向两个级分中加入p-BPA并测量<11>1H-NMR。在SGF-p-BPA体系中，混合后2小时，出现信号。该信号似乎是由于p-BPA-黑色素前体复合物。信号随时间增加，混合后8小时，信号变为宽信号。在LGF p-BPA系统中，没有观察到这种信号。在给药后2小时和10小时，分离仓鼠的黑素瘤，并测量<11>1H-NMR。在所有样品中都没有观察到p-BPA-黑色素前体的峰，但是在所有样品中都观察到硼酸的峰<11>。黑色素可分为两种类型，即：例如，褐黑素和真黑素。p-BPA抑制两种黑色素的形成。p-BPA比m-BPA更易与单糖形成络合物。p-BPA与多巴胺的复合物。少

项目成果

Measurement of Optical Purity of p-BPA-Tyrosine Dipeptide

对-BPA-酪氨酸二肽光学纯度的测定

• 发表时间: 2002
• 期刊: Peptide Science 2001(H.Aoyagi ed), The Japanese Peptide Society
• 作者: N.Sato;K.Yoshino;K.Kitta;Y.Saitake;J.Hiratsuka;M.Ichihashi
• 通讯作者: M.Ichihashi

Structure Determination of p-Boronophenylalanine-Fructose Complex Using ^1J_<cc> coupling Constants

使用 ^1J_<cc> 耦合常数测定对硼苯丙氨酸-果糖复合物的结构

• 发表时间: 2001
• 期刊: Frontiers in Neutron Capture Therapy(M.F.Hawthorne et al. eds.)(Kluwer Academic/Plenum Publishers, New York)
• 作者: M.Kitazawa;K.Yoshino
• 通讯作者: K.Yoshino

Biodistribution of boron concentration on melanoma-bearing hamsters after administration of p-, m-, o-boronophenylalanine

• DOI: 10.1111/j.1349-7006.2000.tb00965.x
• 发表时间: 2000-04-01
• 期刊: JAPANESE JOURNAL OF CANCER RESEARCH
• 作者: Hiratsuka, J;Yoshino, K;Mishima, Y
• 通讯作者: Mishima, Y

Structure Determination of p-Boronophenylalanine-Fructose Complex Using 1^J_<cc> coupling Constants

使用 1^J_<cc> 耦合常数测定对硼苯丙氨酸-果糖复合物的结构

• 发表时间: 2001
• 期刊: Frontiers in Neutron Capture Therapy (M.F.Hawthorne et al.eds.)(Kluwer Academic / Plenum Publishers New York)
• 作者: M.Kitazawa;K.Yoshino
• 通讯作者: K.Yoshino

A Further Mechanism Study of Boron Accumulation to and Release from Melanoma with p-Boronophenylalanine New York

对硼苯丙氨酸对黑色素瘤中硼积累和释放的进一步机制研究 纽约

• 发表时间: 2000
• 期刊: Frontiers in Neutron Capture Therapy (M.F.Hawthorne et al.eds.)(Kluwer Academic / Plenum Publishers)
• 作者: K.Yoshino;M.Kamijo;M.Kimura;Y.Mishima;H.Kondoh;M.Kadota;S.Ito;K.Wakamatsu;H.Kakihana
• 通讯作者: H.Kakihana