P-BORONOPHENYLALANINE IN NEUTRON CAPTURE THERAPY

来自10B（n，α）7 Li反应的反应产物具有 在组织中约10微米的范围内，并且已知具有高的 生物有效性。 B-10在肿瘤中的定位 选择性照射癌细胞内的中子辐射 领域 总的目标是充分利用中子的潜力 通过利用硼化化合物的捕获疗法（NCT）， 在肿瘤中显示出选择性的生理定位， 超热中子束， 穿透和减少表面组织暴露， 传统的中子束 苯丙氨酸的硼化类似物 将在鼠黑素瘤模型中进行测试。 已知的是 黑色素性黑色素瘤活跃地代谢芳香族氨基酸 用作色素黑色素合成中的前体。 在初步的实验中， 对硼苯丙氨酸（BPA）小鼠导致选择性 硼在肿瘤中的累积达到最大值 注射后约6小时的值。 中硼浓度 肿瘤在有效NCT所需的范围内（15 - 30 微克10B/克）。 肿瘤中硼含量与肿瘤中硼含量的比值 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辐照后。 这些结果支持BPA被运输到 黑色素瘤细胞通过芳香族氨基酸转运 系统. 从这个生物化学模型中推理， 芳香族氨基酸转运的大量文献， 代谢，提出了旨在优化 黑色素瘤细胞的选择性硼负荷，同时保持 正常组织硼含量适合NCT。 具体方面 包括：（1）运输系统的承载能力; (2)BPA运输的抑制剂;（3）硼的代谢命运 以及（4）递送BPA或抑制剂的替代途径 黑色素生物合成到黑色素瘤细胞。 虽然最终目标是治疗人类癌症， 临床治疗不是本研究计划的一部分。 这项工作， 然而，应建立NCT的可行性， 实验性黑色素瘤，以及 原则，辐射灭活其他类型的肿瘤的基础上， 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.