41019570 - Journal of Neuro-Oncology 62: 3345, 2003. 2003...

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Unformatted text preview: Journal of Neuro-Oncology 62: 3345, 2003. 2003 Kluwer Academic Publishers. Printed in the Netherlands . A critical assessment of boron target compounds for boron neutron capture therapy M. Frederick Hawthorne and Mark W. Lee Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA Key words: boron neutron capture therapy, boron-containing drugs, boron target species, boron agent evaluation, borane compound synthesis, borane production Summary 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 tar- get 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 nec- essarily 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 develop- ment, 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. Introduction The two components of the binary boron neutron capture therapy (BNCT) procedure [1] are an abun- dance of capturable slow neutrons at the tumor site and a significantly elevated concentration of boron-10 nuclei in the malignant cell targeted for destruction by high LET fission products ( 3 He and 7 Li nuclei) having truncated trajectories. In this contribution we are con- cerned with the development of boron-containing tar-...
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41019570 - Journal of Neuro-Oncology 62: 3345, 2003. 2003...

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