P-BORONOPHENYLALANINE IN NEUTRON CAPTURE THERAPY

由10B(n，α)7Li反应生成的反应产物具有 在组织中的范围约为10微米，并已知具有高 生物学效果。B-10在肿瘤许可中的定位 肿瘤细胞在中子辐射中的选择性照射 菲尔德。总体目标是充分利用中子的潜力。 利用含硼化合物进行俘获治疗(NCT) 在肿瘤中显示选择性的生理定位，以及 超热中子束使组织得到改善 穿透性和减少表面组织暴露相比 传统的中子束。一种苯丙氨酸的硼化类似物 将在小鼠黑色素瘤模型中进行测试。众所周知， 黑色素性黑色素瘤活跃代谢芳香氨基酸 用作合成黑色素的前体。 在初步实验中，注射携带黑色素瘤的 给予对硼苯丙氨酸(BPA)的小鼠导致选择性 硼在肿瘤中的积聚达到最大值 价值约在注射后6小时。水中硼的浓度 肿瘤处于有效NCT所需的范围内(15-30 微克10B/克)。肿瘤中的硼与人体内的硼的比值 血液和肌肉分别约为5-10和5。使用这些 我们已经能够获得肿瘤生长控制的条件 在医学研究反应堆进行中子照射之后。 这些结果支持了双酚A被输送到 通过芳香氨基酸转运的黑色素瘤细胞 系统。从这个生化模型中进行推理，并借鉴 关于芳香族氨基酸运输和运输的大量文献 新陈代谢，提出了旨在优化 黑色素瘤细胞选择性载硼的实验研究 正常组织中的硼含量适合于NCT。具体方面 涉及的问题有：(1)运输系统的承载能力； (2)双酚A转运抑制剂；(3)硼的代谢去向 原子；和(4)输送双酚A或抑制剂的替代途径 黑色素生物合成黑色素瘤细胞。 虽然最终目标是治疗人类癌症， 临床治疗不是这项研究计划的一部分。这部作品， 然而，应建立国家技术转换的可行性 实验性黑色素瘤，通过延伸潜在的 原理，辐射灭活其他类型的肿瘤基于 含硼代谢物的生理定位。

Reaction products from the 10B(n, alpha)7 Li reaction have a range of about 10 microns in tissue and are known to have a high bilogical effectiveness. Localization of B-10 in tumor permits selective irradiation of cancer cells within the neutron radiation field. The overall aim is to exploit the full potential of neutron capture therapy (NCT) by utilizing boronated compounds which show selective phsiological localization in tumors, and an epithermal neutron beam which allows improved tissue penetration and a reduced surface tissue exposure compared to conventional neutron beams. A boronated analog of phenylalanine will be tested in a murine melanoma model. It is known that melanotic melanomas actively metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. In preliminary experiments, the injection of melanoma-bearing mice with p-boronophenylalanine (BPA) resulted in a selective accumulation of boron in the tumor which reached maximum values about 6 hours post-injection. The concentration of boron in tumor is within the range needed for effective NCT (15-30 micrograms 10B/gram). The ratio of boron in tumor to that in blood and muscle is about 5-10 and 5 respectively. Using these conditions we have been able to obtain tumor growth control following neutron irradiation at the Medical Research Reactor. These results support the assumption that BPA is transported into the melanoma cells via the aromatic amino acid transport systems. Reasoning from this biochemical model and drawing on the extensive literature of aromatic amino acid transport and metabolism, studies are proposed which are intended to optimize the selective boron loading of melanoma cells while keeping the normal tissue boron content suitable for NCT. Specific aspects addressed are: (1) the carrying capacity of the transport system; (2) inhibitors of BPA transport; (3) the metabolic fate of the boron atom; and (4) alternative routes for delivering BPA or inhibitors of melanin biosynthesis into melanoma cells. Although the ultimate goal is therapy of cancer in human beings, clinical treatment is not part of this research plan. This work, however, should establish the feasibility of NCT in an experimental melanoma and, by extension of the underlying principles, radiation inactivation of other types of tumors based on physiological localization of boron-containing metabolites.