A critical assessment of boron target compounds for boron neutron capture therapy
A critical assessment of boron target compounds for boron neutron capture therapy
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DOI：
10.1007/bf02699932
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发表时间：
2003-03-01
影响因子：
3.9
通讯作者：
Lee, MW
中科院分区：
文献类型：
--
作者：
Hawthorne, MF;Lee, MW
硼中子俘获疗法（BNCT）自1936年由Locher提出和第二次世界大战期间核能的发展以来，经历了巨大的发展。随后的冷战催生了多面体硼烷化学的全新领域，核反应堆技术迅速发展，可用于BNCT的反应堆数量也相应增加。这一努力主要是为了根除多形性胶质母细胞瘤（GBM）和黑色素瘤，而对其他类型的恶性肿瘤的兴趣减少。BNCT所需的硼- 10靶化合物的设计和合成并没有被引导到GBM或黑色素瘤所需的那些类型的化合物中。因此，已知许多潜在有用的硼制剂，除了粗略的检查外，尚未进行生物学评估，只有三种硼- 10富集靶种在美国食品和药物管理局的研究新药分类后被批准用于人类使用；BSH， BPA和GB- 10。所有正在进行的GBM和黑色素瘤的临床试验都必须使用这三种物质中的一种，而且大多数情况下使用BPA。由于生物和化学的最新进展，缺乏对高级化合物评估和化合物发现的有力支持，BNCT的进一步发展目前陷入停滞。BNCT疗效超过目前可用方案的严格证明尚未实现。本文讨论了化合物发展的历史、化合物分类等当代问题以及阻碍未来发展的问题。后者包括在其发展的所有阶段对新的（和现有的）硼靶点候选物进行生物学评价的手段，以及用于临床试验和其他方面的硼靶点物种的大规模合成。如果给予临床治疗疾病选择的自由，如果一项公认的研究证明疗效得到改善，BNCT的未来是光明的。最终，BNCT将以某种形式商业化。
Boron neutron capture therapy ( BNCT) has undergone dramatic developments since its inception by Locher in 1936 and the development of nuclear energy during World War II. The ensuing Cold War spawned the entirely new field of polyhedral borane chemistry, rapid advances in nuclear reactor technology and a corresponding increase in the number to reactors potentially available for BNCT. This effort has been largely oriented toward the eradication of glioblastoma multiforme ( GBM) and melanoma with reduced interest in other types of malignancies. The design and synthesis of boron- 10 target compounds needed for BNCT was not channeled to those types of compounds specifically required for GBM or melanoma. Consequently, a number of potentially useful boron agents are known which have not been biologically evaluated beyond a cursory examination and only three boron- 10 enriched target species are approved for human use following their Investigational New Drug classification by the US Food and Drug Administration; BSH, BPA and GB- 10. All ongoing clinical trials with GBM and melanoma are necessarily conducted with one of these three species and most often with BPA. The further development of BNCT is presently stalled by the absence of strong support for advanced compound evaluation and compound discovery driven by recent advances in biology and chemistry. A rigorous demonstration of BNCT efficacy surpassing that of currently available protocols has yet to be achieved. This article discusses the past history of compound development, contemporary problems such as compound classification and those problems which impede future advances. The latter include means for biological evaluation of new ( and existing) boron target candidates at all stages of their development and the large- scale synthesis of boron target species for clinical trials and beyond. The future of BNCT is bright if latitude is given to the choice of clinical disease to be treated and if a recognized study demonstrating improved efficacy is completed. Eventually, BNCT in some form will be commercialized.