Abstract:
Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form, which undergoes instantaneous nuclear fission to produce high-energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with high-grade gliomas. First, we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. Second, we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. Third, although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.
摘要:
硼中子俘获疗法(BNCT)是一种基于稳定同位素硼10发生的核俘获和裂变反应的癌症治疗方式,用适当能量的中子辐照以产生不稳定形式的硼11,它经历瞬间核裂变产生高能,杀肿瘤的α颗粒。这篇综述的主要目的是提供临床上使用的第一种药物的更新,硼辛酸钠(BSH),由日本神经外科医生HatanakaHiroshi治疗脑肿瘤患者和第二种药物,硼苯丙氨酸(BPA),日本皮肤科医生YutakaMishima首先在临床上用于治疗皮肤黑色素瘤患者。随后,BPA已成为用作硼递送剂的主要药物,用于治疗患有多种癌症的患者。特别是脑肿瘤和头颈部复发性肿瘤。本综述的重点将是进行的初步研究,以确定BSH和BPA的药代动力学和药效学及其在高级别神经胶质瘤患者给药后在肿瘤和正常组织中的生物分布,以及随后的临床应用治疗高级别神经胶质瘤患者。首先,我们将总结在日本与BSH以及随后在我们自己的机构进行的研究,俄亥俄州立大学,以及其他几个团体的。第二,我们将描述在日本使用BPA进行的研究,然后在美国进行的研究导致将其用作临床上用于BNCT的主要药物。第三,尽管一直在努力开发新的更好的BNCT硼释放剂,这些都没有经过临床评估。本报告将为在BNCT临床使用前新的硼递送剂的未来临床评估提供指导。