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Abstract

To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and blood was investigated in 11 newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kg body weight 2.5-16 hrs prior to tumor removal. The quantitative distribution of 10B was determined by prompt gamma ray spectrometry and/or alpha-track autoradiography. 10B distribution in tumors was heterogeneous, +/- 25% of scattering at the microscopic level, and the distribution was also heterogeneous at the tissue level. 10B concentration in blood decreased in bi-exponential decay as a function of the time after the end of the administration. The T/B ratio showed non-exponential increase with large variation. The maximum T/B ratio would be around 1. The tumor/normal brain (T/N) ratio of 10B concentration was 11.0 +/- 3.2. The 10B content in normal brain is originated in vascular 10B in parenchyma, since the 10B content in normal brain to blood (N/B ratio) being compatible with the blood content in parenchyma. These values allow for BNCT, using thermal neutrons, on brain tumors located less than approximately 3.3 cm in depth from the brain surface of neutron incidence, providing that the dose on the normal endothelium is controlled to less than the tolerance limit. In our preliminary study of BNCT, a 31% 3-year survival was achieved over all for 16 glioblastoma patients and a 50% 2-year survival was achieved on 8 glioblastoma patients in our recent dose escalation study based on these data.

The use of radiosensitizing agents in the therapy of glioblastoma multiforme—a comprehensive review

“…With preferred uptake in tumor tissue, the treatment aims to achieve high toxicity in tumor cells with minimal risk of damaging surrounding tissue [ 82 ]. Beginning in 1994, several study groups have evaluated this concept as an alternative treatment method for malignant glioma [ 82 – 85 ], optimizing the concepts of dose delivery and monitoring [ 86 – 89 ] as well as exploring concepts of intraoperative treatment [ 90 ], combination of different boron sources (BPA + BSH, [ 91 , 92 ]), different types of radiation (neutrons + photons, [ 93 , 94 ]) and palliative approaches [ 95 ]. But while several studies showed promising results [ 89 – 92 , 96 , 97 ] as well as histopathologic proof of treatment response [ 98 , 99 ], the benefit did not exceed standard therapy with photon irradiation and concurrent chemotherapy with TMZ [ 100 ].…”

“…[ 84 ] 1997 BPA 130–250 mg/kg 18 Maximum of 52.6 ± 4.9 Gy-Eq Minimum of 25.2 ± 4.2 Gy-Eq to the tumor Feasibility of the concept, no adverse events Takagaki et al. [ 85 ] 1997 BSH 20 mg/kg 11 N/A 2‑year OSR: 50% Chadha et al. [ 86 ] 1998 BPA 250 mg/kg 10 Minimum of 20 to 32.3 Gy-Eq to the tumor Median OS: 13.5 months Palmer et al.…”

“…Novel approaches in this strategy, like PARP inhibition or the use of compound-gadolinium also failed to show statistically significant benefit as an asset to the implemented Stupp regimen (MGd: 15.6 months [ 70 ], PARPi: 12.7 months [ 60 ]). A very interesting approach is the concept of BNCT, which has already shown some encouraging results (median OS of 23.2 months [ 90 ], 2‑year OSR of 50% [ 85 ]) but the complexity of the treatment results in overall low case numbers. Future studies with larger cohorts are needed to validate this promising data.…”

An analysis of the structure of the compound biological effectiveness factor

“…A healthy blood–brain barrier inhibits penetration of BSH into the central nervous system (CNS) [ 7 , 8 ]. Consequently, the CBE factor for BSH to the spinal cord is considered to be derived from the radiation dose irradiated to the vasculature from the intraluminal side.…”

Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications

“…BNCT has obtained promising clinical results for several pathologies as head and neck tumors including recurrent pathologies [3,5,7], malignant brain tumors [8,9], and malignant melanoma [10,11]. Regardless of these reports, there are still several limitations.…”