Report on the first patient group of the phase I BNCT trial at the LVR-15 reactor

Burian, J.; Marek, M.; Rataj, Jan; Flibor, S.; Rejchrt, J.; Viererbl, L.; Sus, F.; Honová, Hana; Petruželka, Luboš; Prokeš, K.; Tovaryś, F; Dbalý, Vladimír; Beneš, Vladimı́r; Kozler, Petr; Honzátko, J.; Tomandl, I.; Mareš, V

doi:10.1016/s0531-5131(03)01515-2

Cited by 16 publications

(9 citation statements)

References 4 publications

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“…Clinical trials for patients with brain tumors were initiated at several locations, including (a) the BMRR at BNL from 1994 to 1999 for glioblastoma multiforme using BPA with one or two neutron radiations, given on consecutive days (161 -163); (b) the MITR from 1996 to 1999 for glioblastoma multiforme and i.c. melanoma (164,165); (c) the High Flux Reactor, Petten, the Netherlands, and the University of Essen in Germany in 1997 using BSH (166) (130); and (f) the Nuclear Research Institute reactor in Rez, Czech Republic, by Tovarys using BSH (167). The number of patients treated in this study is small and the follow-up is still rather short.…”

Section: Clinical Studies Of Boron Neutron Capture Therapy For Braintmentioning

confidence: 96%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

924

666

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Background: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer A particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. Boron Delivery Agents: Two boron drugs have been used clinically, sodium borocaptate (Na 2 B 12 H 11 SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations (f20 Ag/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boroncontaining amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. Clinical Trials: Current or recently completed clinical trials have been carried out inJapan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of ''debulking'' surgery to remove as much of the tumor as possible, followed by BNCTat varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. Conclusions: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCTcould move forward as a treatment modality.

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Section: Clinical Studies Of Boron Neutron Capture Therapy For Braintmentioning

confidence: 96%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

924

666

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“…10 Clinical phase I/II trials were initiated in the USA and in several European countries. [11][12][13][14][15][16] The two most commonly used compounds for BNCT ( Fig. 1) are BSH-sodium mercaptoundecahydrocloso-dodecaborane (Na 2 B 12 H 11 SH)-and boronated phenylalanine (BPA).…”

Section: Bnctmentioning

confidence: 99%

Biomedical applications of10B and11B NMR

Bendel

2005

NMR Biomed.

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This review focuses mainly on the detection and investigation of molecules used for boron neutron capture therapy (BNCT) by 10 B and 11 B NMR. In this binary radiation treatment, boron-containing molecules (also called 'BNCT agents') enriched in the 10 B isotope, are targeted to the tumor, and irradiated with thermal or epithermal neutrons. Capture of these neutrons by 10 B nuclei generates cell-damaging radiation, confined to single cell dimensions. NMR research efforts have primarily been applied in two directions: first, to investigate the metabolism and pharmaco-kinetics of BNCT agents invivo, and second, to use localized NMR spectroscopy and/or MRI for non-invasive mapping of the administered molecules in treated animals or patients. While the first goal can be pursued using 11 B NMR for natural-abundance samples (80% 11 B / 20% 10 B), molecules used in the actual treatment are >95% enriched in 10 B, and must therefore be detected by 10 B NMR. Both 10 B (spin 3) and 11 B (spin 3/2) are quadrupolar nuclei, and their typical relaxation times, in common BNCT agents in biological environments, are rather short. This poses some technical challenges, particularly for MRI, which will be reviewed, along with possible solutions. The first attempts at 11 B NMR and MRI detection of BNCT agents in biological tissue were conducted over a decade ago. Since then, results from 11 B MRI in laboratory animals and in humans have been reported, and 11 B NMR spectroscopy provided interesting and unique information about the metabolism of some BNCT agents in cultured cells. 10 B NMR was applied either 'indirectly' (in double-resonance experiments involving coupled protons), but also by direct 10 B MRI in mice. However, no results involving the NMR detection of 10 B-enriched compounds in treated patients have been reported yet.

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“…Clinical studies of second-generation boron delivery agents are listed in Table 1 [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ]. Current research originates from many institutions around the world.…”

Section: Application Of Second-generation Boron Delivery Agentsmentioning

confidence: 99%

Boron Neutron Capture Therapy: Clinical Application and Research Progress

Cheng

Liu³

2022

Current Oncology

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Boron neutron capture therapy (BNCT) is a binary modality that is used to treat a variety of malignancies, using neutrons to irradiate boron-10 (10B) nuclei that have entered tumor cells to produce highly linear energy transfer (LET) alpha particles and recoil 7Li nuclei (10B [n, α] 7Li). Therefore, the most important part in BNCT is to selectively deliver a large number of 10B to tumor cells and only a small amount to normal tissue. So far, BNCT has been used in more than 2000 cases worldwide, and the efficacy of BNCT in the treatment of head and neck cancer, malignant meningioma, melanoma and hepatocellular carcinoma has been confirmed. We collected and collated clinical studies of second-generation boron delivery agents. The combination of different drugs, the mode of administration, and the combination of multiple treatments have an important impact on patient survival. We summarized the critical issues that must be addressed, with the hope that the next generation of boron delivery agents will overcome these challenges.

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Report on the first patient group of the phase I BNCT trial at the LVR-15 reactor

Cited by 16 publications

References 4 publications

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Biomedical applications of10B and11B NMR

Boron Neutron Capture Therapy: Clinical Application and Research Progress

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