Status Report on the European Clinical Trial of BNCT at Petten (EORTC Protocol 11961)

Sauerwein, W.; Moss, Ray; Hidéghety, Katalin; Stecher‐Rasmussen, F.; Vries, M. de; Reulen, H. J.; Götz, Claudia; Paquis, Philippe; Grochulla, Frank; Haselsberge, K.; Wolbers, J.G.; Rassow, J.; Pignol, J.; Watkins, P.; Vroegindeweij, C.; Ravensberg, K.; Garbe, Stephan; Wiestler, Otmar D.; Turowski, Bernd; Zanella, Friedhelm E.; Touw, Daan; Siefert, Axel; Huiskamp, R.; Fankhauser, Heinz; Gabel, Detlef

doi:10.1007/978-1-4615-1285-1_7

Cited by 7 publications

(6 citation statements)

References 4 publications

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“…Neutron beams to deliver sufficient thermal neutrons to deep-seated tumors have been developed, and are available in the U. S., Japan, and Europe. [3][4][5][6][7][8] Epithermal beams can penetrate healthy tissues to deposit a lethal dose to deep-seated tumors while sparing most healthy tissues.…”

Section: Introductionmentioning

confidence: 99%

Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine

1999

Med. Phys.

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Previous dosimetry studies for boron neutron capture therapy have often neglected the thermal neutron self-shielding effects caused by the 10B accumulation in the brain and the tumor. The neglect of thermal neutron flux depression, therefore, results in an overestimation of the actual dose delivery. The relevant errors are expected to be more pronounced when boronophenylalanine is used in conjunction with an epithermal neutron beam. In this paper, the boron self-shielding effects are calculated in terms of the thermal neutron flux depression across the brain and the dose delivered to the tumors. The degree of boron self-shielding is indicated by the difference between the thermal neutron fluxes calculated with and without considering a 10B concentration as part of the head phantom composition. The boron self-shielding effect is found to increase with increasing 10B concentrations and penetration depths from the skin. The calculated differences for 10B concentrations of 7.5-30 ppm are 2.3%-8.3% at 2.3 cm depth (depth of the maximum brain dose) and 4.6%-17% at 7.3 cm depth (the center of the brain). The additional self-shielding effects by the 10B concentration in a bulky tumor are investigated for a 3-cm-diam spherical tumor located either near the surface (3.3 cm depth) or at the center of the brain (7.3 cm depth) along the beam centerline. For 45 ppm of 10B in the tumor and 15 ppm of 10B in the brain, the dose delivered to the tumors is approximately 10% lower at 3.3 cm depth and 20% lower at the center of the brain, compared to the dose neglecting the boron self-shielding in transport calculations.

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Section: Introductionmentioning

confidence: 99%

Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine

1999

Med. Phys.

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“…Previously reported pharmacokinetic analyses of BSH have been based upon data derived from analytical methods that determined the total boron concentration of samples, irrespective of its chemical form following the administration of the drug. − ,,− Although these studies have provided data necessary for the development of BSH as a therapeutic agent, the true pharmacokinetics of the drug in humans has remained undetermined. We have developed an LC/MS assay for the quantitation of BSH in plasma and have used this to generate pilot data for the pharmacokinetics of BSH in brain tumor patients.…”

Section: Resultsmentioning

confidence: 99%

“…Sodium undecahydromercapto -closo- dodecaborate , commonly referred to as sodium borocaptate (Na 2 B 12 H 11 SH), or BSH, is a polyhedral borane that has been used clinically for BNCT of brain tumors in Japan , and Europe . A high-performance liquid chromatographic (HPLC) assay has been developed for BSH that uses monobromobimane to form an ultraviolet (UV)-absorbing adduct with the drug.…”

mentioning

confidence: 99%

Electrospray Ionization Mass Spectrometry Coupled To Reversed-Phase Ion-Pair High-Performance Liquid Chromatography for Quantitation of Sodium Borocaptate and Application To Pharmacokinetic Analysis

et al. 2002

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We have developed a quantitative assay using electrospray ionization mass spectrometry coupled to reversed-phase ion-pair liquid chromatography (LC/MS) for quantitation of sodium borocaptate (BSH) in human plasma. The assay was developed using a Micromass Q-TOF II mass spectrometer equipped with an orthogonal electrospray source. The mobile phase was a 1:1 solution of methanol and 5 mM aqueous tetrabutylammonium acetate flowing at 0.2 mL/min, and the chromatography was performed using a Machery-Nagel Nucleosil C18 column. Plasma samples from patients who had received an intravenous infusion of sodium borocaptate (Na2B12H11SH), frequently referred to as BSH, were prepared for analysis by precipitation with acetonitrile. Following this, the supernatants were collected, and 40 μL was injected onto the column for analysis. The LC/MS assay was linear over a BSH plasma concentration range of 20−0.5 μg/mL with acceptable variability for both intra- and interassay precision. The LC/MS assay was used to generate pilot pharmacokinetic data for the plasma disposition of BSH in humans. The disposition of BSH was found to be consistent with a two-compartment model with first-order elimination from the central compartment. The mean total body plasma clearance was 95.7 ± 30.8 mL/min and the harmonic mean terminal half-life was 3.6 h.

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“…The first clinical successes were reported by Prof. Dr. Hatanaka et al [9,10], later on a number of other groups followed and proved positive effects on patients treated by BNCT [11][12][13][14][15][16][17][18][19][20]. After about 60 years research and development on the reactor-based BNCT, the technical efforts are focused on the accelerator-based neutron sources to be installed in hospitals [21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Neutron beams implemented at nuclear research reactors for BNCT

2017

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A: This paper presents a survey of neutron beams which were or are in use at 56 Nuclear Research Reactors (NRRs) in order to be used for BNCT, either for treatment or research purposes in aspects of various combinations of materials that were used in their Beam Shaping Assembly (BSA) design, use of fission converters and optimized beam parameters. All our knowledge about BNCT is indebted to researches that have been done in NRRs. The results of about 60 years research in BNCT and also the successes of this method in medical treatment of tumors show that, for the development of BNCT as a routine cancer therapy method, hospital-based neutron sources are needed. Achieving a physical data collection on BNCT neutron beams based on NRRs will be helpful for beam designers in developing a non-reactor based neutron beam. K: Instrumentation for neutron sources; Instrumentation for particle-beam therapy 1Corresponding author.

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Status Report on the European Clinical Trial of BNCT at Petten (EORTC Protocol 11961)

Cited by 7 publications

References 4 publications

Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine

Boron self-shielding effects on dose delivery of neutron capture therapy using epithermal beam and boronophenylalanine

Electrospray Ionization Mass Spectrometry Coupled To Reversed-Phase Ion-Pair High-Performance Liquid Chromatography for Quantitation of Sodium Borocaptate and Application To Pharmacokinetic Analysis

Neutron beams implemented at nuclear research reactors for BNCT

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