Article Origins of BNCT Year 1994

Dedication to Sweet and Hatanaka

International Journal of Radiation Oncology*Biology*Physics, 1994

Authors:   Rolf F. Barth, Albert H. Soloway
Journal: International Journal of Radiation Oncology*Biology*Physics
Abstract: The development of Boron Neutron Capture Therapy (BNCT) is linked to two individuals, William H. Sweet and Hiroshi Hatanaka. It was Sweet who first realized the clinical potential of BNCT as a modality to treat brain tumors. The pioneering work of Sweet and his colleagues at the Massachusetts General Hospital, the Massachusetts Institute of Technology, and the Brookhaven National Laboratory in the 1950s and early 1960s was directed towards treating patients with recurrent high grade gliomas using several different boron compounds as the capture agent. Unfortunately, none of these compounds demonstrated the requisite tumor selectivity that we now know is essential. Although the clinical results were disappointing, attempts to identify boron containing chemical compounds that demonstrated a higher degree of tumor selectivity continued on into the mid- 1960s. It was at this time that Hiroshi Hatanaka, a Fullbright Scholar from Japan, joined Sweet’s laboratory and became actively involved with one of us (A.H.S.) on a research project that led to the discovery of a sulfhydryl containing polyhedral borane, which appeared to have tumor localizing properties. This compound, known either as di-sodium undecahydro close, dodecaborate (Na2BiZHl ,SH) or sodium borocaptate (BSH), demonstrated high tumor: brain and tumor: blood ratios following ad- ministration to tumor bearing mice. Upon his return to Japan in 1965, Hatanaka initiated a clinical trial in patients with high grade gliomas using a combination of surgery and BNCT with sodium borocaptate as the capture agent. Between 1966 and 1993, Hatanaka has treated approximately 120 patients, a significant subset of which had glioblastomas. Although the nuclear reactors used as neutron sources were far from ideal and many of the patients had either deeply seated or recurrent tumors, his results, reported in this issue of the Journal, have stimulated interest and controversy in BNCT. Patients with glioblastomas have survived for periods ranging from 5 to 15 years, and there has been a trend towards increased survival among another group of patients with more superficially located tumors. Despite the criticism by some neurosurgeons and radiation therapists, who viewed his efforts with skepticism, in part because of the clinical failures in the United States, Hatanaka persevered, and as a result of his efforts, there is a growing realization that BNCT may have great potential as a radiotherapeutic modality.