Department of Pathology, The Ohio State University, Columbus, Ohio, USA.
Department of Radiation Oncology, The Ohio State University, Columbus, Ohio, USA.
Cancer Commun (Lond). 2024 Aug;44(8):893-909. doi: 10.1002/cac2.12582. Epub 2024 Jul 8.
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.
硼中子俘获治疗（BNCT）是一种基于核捕获和裂变反应的癌症治疗方法，当稳定同位素硼-10 被适当能量的中子辐照时，会产生不稳定形式的硼-11，硼-11 会立即发生核裂变，产生高能、杀肿瘤的阿尔法粒子。本综述的主要目的是提供日本神经外科医生平田博司（Hiroshi Hatanaka）首次临床使用的第一种药物——硼替佐米（BSH），以及日本皮肤科医生三岛由纪夫（Yutaka Mishima）首次临床使用的第二种药物——硼苯丙氨酸（BPA）的最新进展。随后，BPA 成为用于治疗多种癌症患者（特别是脑肿瘤和头颈部复发性肿瘤）的主要硼供体药物。本综述的重点将放在最初进行的研究上，这些研究旨在定义 BSH 和 BPA 的药代动力学和药效学及其在高等级神经胶质瘤患者给药后的体内分布，以及它们随后在治疗高等级神经胶质瘤患者中的临床应用。首先，我们将总结在日本进行的 BSH 研究，以及随后在我们的机构（俄亥俄州立大学）和其他几个小组进行的研究。其次，我们将描述在日本进行的 BPA 研究，以及随后在美国进行的研究，这些研究导致 BPA 被用作 BNCT 的主要药物。第三，尽管人们一直在努力开发用于 BNCT 的新的更好的硼供体药物，但这些药物都尚未进行临床评估。本报告将为 BNCT 临床前评估新的硼供体药物提供指导。
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