Microanalytical techniques for boron analysis using the 10B(n,α)7Li reaction

Fairchild, R.G.; Gabel, Detlef; Laster, Zvi; Greenberg, D.; Kiszenick, W.; Micca, Peggy L.

doi:10.1118/1.595962

Cited by 77 publications

(13 citation statements)

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“…in a fructose solution at a dose of 700 mg kg -1 (34 mg 10 B kg -1 ) as described previously . Concentrations of 10 B in solutions of BSH and BPA were determined using direct current plasma atomic emission spectroscopy (DCP-AES) and prompt gamma analysis (Fairchild et al, 1986;Barth et al, 1991).…”

Section: Methodsmentioning

confidence: 99%

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

et al. 2000

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Summary Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 ( 10 B) in the oral mucosa to the biological effectiveness of the 10 B(n,α) 7 Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10 B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10 B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10 B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10 B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10 B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10 B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10 B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 ± 0.02. This compares with a previously published CBE factor for BPA of 4.87 ± 0.16. It was concluded that variations in the microdistribution profile of 10 B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiationinduced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10 B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT.

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Section: Methodsmentioning

confidence: 99%

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

et al. 2000

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“…Boron concentrations of such aqueous samples were analyzed by prompt-y spectrometry (12). Internal controls were samples of normal tissue to which an aqueous solution of 10B-enriched boric acid (U.S. National Bureau of Standards) was added to bring the total net weight to 1.00 ± 0.01 g. (6).…”

Section: Methodsmentioning

confidence: 99%

Boron neutron capture therapy of intracerebral rat gliosarcomas.

Joel

Fairchild

Laissue

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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The efficacy ofboron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na41°B24H22S2, at a rate of 45-50 pg of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 pig/ml in a group of 12 gliosarcoma-bearing rats and 45 /Ag/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 pg/g, respectively.On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW-min ofradiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of -2.0 x 1012 or "'3.0 x 1012 n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MWimin) or 28 (7.5 MW-min) days. The 12 rats that received 5 MW-min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived >15 months. In the 7.5 MWmin group, the median survival time is not calculable since 6 of the 10 animals remain alive >10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation.It is postulated that successful boron neutron capture therapy (BNCT) of human gliomas would require the preferential accumulation of 10B in the tumor (1), low levels of 10B in the blood and in the surrounding normal tissues, and the delivery of sufficiently high thermal neutron fluences at tumor sites (2). The initial clinical trials of BNCT of malignant brain tumors, conducted in the U.S.A. from 1951 through 1961, were disappointing, apparently because some of these conditions were not fulfilled (3).The polyhedral sulfhydryl borane (monomer), Na2B12-H11SH, was first investigated in the 1960s for possible use in BNCT (4). Evidence in animal tumor models indicates that tumor uptake after administration of the sulfhydryl borane dimer (Na4B24H22S2) is about double the tumor uptake after administration of equal amounts of boron as monomer (5, 6).Furthermore, it was observed that the decrease in tumor boron concentration is much slower after infusion of dimer than of monomer (6). Studies in rats bearing transplanted cerebral gliosarcomas indicate that slow infusion of dimer at the rate of =50 ug of 10B per g of body weight per day for 3 days consistently yields tumor boron concentrations >25 jig of 10B per g with average concentrations in normal brain tissue <2 ,ug of '0B per g. This degree of selective tumor boron uptake should provide an adequate therapeutic gain for BNCT. We used this infusion sched...

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“…For instance, spectrophotometric analysis using different boron complexing reagents has a modest sensitivity, has a relatively low specificity, and is also time-consuming (9, 10). Nuclear techniques require a thermal neutron source (such as a nuclear reactor or a neutron-emitting radioisotope) (11,12); hence, the relative scarcity of instruments did not render such methods very common. The last group of methods is represented by atomic absorption or emission spectroscopy.…”

Section: Figmentioning

confidence: 99%

Determination of Boronophenylalanine in Biological Samples Using Precolumn o-Phthalaldehyde Derivatization and Reversed-Phase High-Performance Liquid Chromatography

Pierro

Lazzarino

Pastore

et al. 2000

Analytical Biochemistry

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A reversed-phase high-performance liquid chromatographic method for the detection of boronophenylalanine is described. Determination was obtained by precolumn reaction of o-phthalaldehyde with a mixture of standard amino acids containing boronophenylalanine and separating the corresponding o-phthalaldehyde derivatives, using a Kromasil C-18, 250 ؋ 4.6 mm, 5-m particle size column, a step gradient with two buffers, a flow rate of 1.2 ml/min, a column temperature of 23°C, and fluorimetric detection (excitation and emission wavelengths of 330 and 430 nm, respectively). The use of such a method for assaying boronophenylalanine in biological samples was tested in neutralized perchloric acid blood and cerebral tissue extracts of rats treated with intracarotid administration of 300 mg/kg of body weight boronophenylalanine. Results of these experiments showed that the present HPLC method represents a valid alternative to currently available analytical techniques for assaying boronophenylalanine based on boron determination in terms of reproducibility, recovery, or sensitivity. Therefore, it is suggested that the present method may routinely be used in all preclinical and clinical studies in which quantification of circulating and tissue concentrations of boronophenylalanine is critical for the application of boron neutron capture therapy.

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Microanalytical techniques for boron analysis using the ¹⁰B(n,α)⁷Li reaction

Cited by 77 publications

References 0 publications

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

Boron neutron capture therapy of intracerebral rat gliosarcomas.

Determination of Boronophenylalanine in Biological Samples Using Precolumn o-Phthalaldehyde Derivatization and Reversed-Phase High-Performance Liquid Chromatography

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