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PubMed2005

Epithermal neutron beams for clinical studies of boron neutron capture therapy: a dosimetric comparison of seven beams.

A comparison of seven epithermal neutron beams used in clinical studies of boron neutron capture therapy (BNCT) in Sweden (Studsvik), Finland (Espoo), Czech Republic (ReZ), The Netherlands (Petten) and the U.S. (Brookhaven and Cambridge) was performed to facilitate sharing of preclinical and clinical results. The physical performance of each beam was measured using a common dosimetry method under conditions pertinent to brain irradiations. Neutron fluence and absorbed dose measurements were performed with activation foils and paired ionization chambers on the central axis both in air and in an ellipsoidal water phantom. The overall quality of each beam was assessed by figures of merit determined from the total weighted dose profiles that assumed the presence of boron in tissue. The in-air specific beam contamination from both fast neutrons and gamma rays ranged between 8 and 65 x 10(-11) cGy(w) cm2 for the different beams and the epithermal neutron flux intensities available at the patient position differed by more than a factor of 20 from 0.2-4.3 x 10(9) n cm(-2) s(-1). Percentage depth dose profiles measured in-phantom for the individual photon, thermal and fast-neutron dose components differed only subtly in shape between facilities. Assuming uptake characteristics consistent with the currently used boronated phenylalanine, all the epithermal beams exhibit a useful penetration of 8 cm or greater that is sufficient to irradiate a lesion seated at the brain midline. The performance of the existing facilities will benefit from the introduction of advanced compounds through improved beam penetrability. This could increase by as much as 2 cm for the purest of beams, although the beam intensities generally need to be increased to between 2-5 x 10(9) n cm(-2) s(-1) to maintain manageable irradiation times. These data provide the first consistent measurement of beam performance at the different centers and will enable a preliminary normalization of the calculated patient dosimetry.

Boron Neutron Capture Therapy↗
PubMed2005

Measured microdosimetric spectra and therapeutic potential of boron neutron capture enhancement of 252Cf brachytherapy.

Californium-252 is a neutron-emitting radioisotope used as a brachytherapy source for radioresistant tumors. Presented here are microdosimetric spectra measured as a function of simulated site diameter and distance from applicator tube 252Cf sources. These spectra were measured using miniature tissue-equivalent proportional counters (TEPCs). An investigation of the clinical potential of boron neutron capture (BNC) enhancement of 252Cf brachytherapy is also provided. The absorbed dose from the BNC reaction was measured using a boron-loaded miniature TEPC. Measured neutron, photon and BNC absorbed dose components are provided as a function of distance from the source. In general, the absorbed dose results show good agreement with results from other measurement techniques. A concomitant boost to 252Cf brachytherapy may be provided through the use of the BNC reaction. The potential magnitude of this BNC enhancement increases with increasing distance from the source and is capable of providing a therapeutic gain greater than 30% at a distance of 5 cm from the source, assuming currently achievable boron concentrations.

Boron Neutron Capture Therapy↗
PubMed2004

Boronic esters as ionophores for potentiometric discrimination of the cis-trans isomeric dicarboxylic acids.

Boronic esters incorporated into a poly(vinyl chloride) (PVC)-supported liquid membrane electrodes have displayed an anionic ionophore properties enabling their use in the potentiometric high-throughput screening procedures. These compounds belong to the class of ligands in which the anion recognition process can be explained on the concept of Lewis type acid-base interactions. Membranes containing boronic esters showed fairly good sensitivity for maleate (cis-isomer) in comparison to fumarate anions (trans-isomer). The potentiometric selectivity coefficients of proposed electrodes proved that common anions did not interfered with the maleate anion determination. The influence of structure of the three boronic esters ionophores on generation of potentiometric signal by developed liquid membrane electrodes was shortly discussed.

Boronic Acids↗
PubMed2003

Carboranylporphyrins for boron neutron capture therapy of cancer.

A major challenge for cancer treatment is the preferential and irreversible killing of tumor cells and minimal damage of normal tissues, both in the site of the malignancy and in the body. The agents used in boron neutron capture therapy (BNCT) are supposed to have the following advantages over many conventional chemotherapeutics: 1) when irradiated with thermal neutrons, an unstable isotope (11)B is formed whose rapid decay yields local and a thermal effect; 2) because the free path of the released particles is close to the cell diameter, the tissues outside the tumor should gain less damage; 3) local radioactivity and heat should be harmful for cells that, in the course of their natural history, acquired the determinants of altered response to many toxic stimuli. However, a higher specificity of damage would be achieved if the drugs accumulate mostly in cancer cells rather than in non-malignant counterparts. Therefore, optimization of agents for BNCT presumes the design of chemicals with improved accumulation/ retention in cancer cells. In particular, carboranyl-substituted porphyrins, the stable conjugates of macrocyclic porphyrins with complex boron-containing polyhedra, are considered good candidates for BNCT due to their uptake by cancer cells and high boron content. Importantly, the proposed mechanisms of pharmacological effects of carboranylporphyrins make these compounds potentially appropriate for elimination of pleiotropically resistant tumor cells.

Antineoplastic Agents↗
PubMedDate not supplied

Liposomal formulations containing sodium mercaptoundecahydrododecaborate (BSH) for boron neutron capture therapy.

Sodium mercaptoundecahydrododecaborate or BSH is a compound most widely used for boron neutron capture therapy (BNCT). Liposome formulations containing BSH, with or without steric stabilization, were prepared as potential agents for delivery of boron compounds for BNCT. Liposomes composed of DPPC/CHOL in a molar ratio 1:1 (PEG concentration: 5 mol%) were prepared having an average diameter in the range of 100-110 nm 200 mu L of liposomes (l.88 mg phospholipid/mouse and 3.5-5.8 mg BSH/kg body weight) were injected in mice via the tail vein. Both types of liposomes resulted in a significant improvement in the circulation time of BSH compared to that obtained previously after injecting free BSH. The mean percent injected BSH remaining in circulation at the end of 24 h was 19% for the PEG-liposomes compared to the corresponding value of 7% for the conventional liposomes. The mean percent uptake by the liver and spleen was not significantly different for the two types of liposomes; the blood/RES ratios were higher for the PEG-liposomes at all time points indicating that a higher fraction of injected BSH was available in circulation. The PEG-liposomes could be further explored as a means of enhance boron drug delivery to tumor cells for BNCT.

Animals↗
PubMed1994

Enhancement of fast neutron beams with boron neutron capture therapy. A mechanism for achieving a selective, concomitant tumor boost.

Both fast neutron radiotherapy and boron neutron capture therapy (BNCT) have been utilized to treat malignant disease. Herein we discuss the potential of combining these treatments to enhance the effectiveness of fast neutron therapy through a concomitant BNCT boost. Using a fast neutron beam generated from a 50 MeV proton on beryllium reaction, we have determined that 0.1% of the beam per microgram of boron-10 per gram of tissue (microgram/g) can be deposited via BNCT. Our mathematical modeling predicts that BNCT enhancement of our beam will lead to an additional 1-2 logs of tumor cell kill for boron-10 concentrations of 30-50 micrograms/g. We have validated this via V-79 cell line in vitro measurements. A Poisson model estimation of how this additional cell kill will influence local tumor control, predicts that BNCT enhancement of fast neutron radiation will lead to a clinically significant improvement in outcome.

Animals↗
PubMed1975

Toxic effects of a new boron containing heterocycle: 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro 3a,4a,4-diazabora-S-indacene.

LD50 values in mice for 4,4,8,8-tetraethyl-3,3a,4,8-tetrahydro-3a,4a,4-diazabora-S-indacene (Myborin) were determined by the ip, po, and sc routes. The LD50 value for ip was 69.5 mg/kg found by the method of Litchfield and Wilcoxon, with upper and lower confidence limits of 77.8 and 62.1 mg/kg. Oral and sc LD50's were approximated after the method of Deichmann and LeBlanc and were found to be 180 mg/kg (po) and 420 mg/kg (sc). Each of these values has a confidence range of +/- 30%. Myborin induced convulsions, hyperreflexia, and death accompanied by tetany when given by either the ip or oral routes. Moreover, Myborin induced porphyria in animals surviving for 24 hr after these routes of administration and in virtually all animals dosed sc. Death by the sc route is probably a result of acute porphyria. Hepatomegaly and skin photosensitivity were demonstrated to be profound. Boron levels in the livers of mice were determined colorimetrically 24 hr after ip injections of Myborin and in untreated control mice. The quantity of boron found in the experimental group was 15.46 mug/g wet liver as compared to 8.11 mug/g wet liver for controls (P less than 0.01). The difference corresponds to 23% of the injected quantity of boron.

Animals↗
PubMed2000

Characterization of peptidyl boronic acid inhibitors of mammalian 20 S and 26 S proteasomes and their inhibition of proteasomes in cultured cells.

Proteasomes are large multisubunit proteinases which have several distinct catalytic sites. In this study a series of di- and tri-peptidyl boronic acids have been tested on the chymotrypsin-like activity of purified mammalian 20 S and 26 S proteasomes assayed with succinyl-Leu-Leu-Val-Tyr-amidomethylcoumarin (suc-Leu-Leu-Val-Tyr-AMC) as substrate. The inhibition of 20 S proteasomes is competitive but only slowly reversible. The K(i) values for the best inhibitors were in the range 10-100 nM with suc-Leu-Leu-Val-Tyr-AMC as substrate, but the compounds tested were much less effective on other proteasome activities measured with other substrates. Free boronic acid inhibitors exhibited equivalent potency to their pinacol esters. Both benzoyl (Bz)-Phe-boroLeu and benzyloxycarbonyl (Cbz)-Leu-Leu-boroLeu pinacol ester inhibited 20 S and 26 S proteasomes with non-ideal behaviour, differences in inhibition of the two forms of proteasomes becoming apparent at high inhibitor concentrations (above 3xK(i)). Both of these compounds were also potent inhibitors of 20 S and 26 S proteasomes in cultured cells. However, gel filtration of cell extracts prepared from cells treated with radiolabelled phenacetyl-Leu-Leu-boroLeu showed that only 20 S proteasomes were strongly labelled, demonstrating differences in the characteristics of inhibition of 20 S and 26 S proteasomes. The usefulness of peptidyl boronic acid inhibitors for investigations of proteasome-mediated protein degradation was confirmed by the observation that Bz-Phe-boroLeu and Cbz-Leu-Leu-boroLeu pinacol ester inhibited NFkappaB activation with IC(50) values comparable to their K(i) values for purified proteasomes. The latter result supports the view that the chymotrypsin-like activity of proteasomes assayed with suc-Leu-Leu-Val-Tyr-AMC is a critical one for protein degradation in cells.

Animals↗
PubMed2000

Calcium and boron for in vitro rooting of Nothofagus nervosa.

Several mineral compounds influence adventitious rooting, and those containing boron and calcium, play an important role. They are associated to the enzyme regulation, cell division, cellular metabolism (induction stage) and roots enlargement (expression stage). The aims of this work were to study the variation of the endogenous calcium and boron concentrations along the rooting, and determine their optimal concentrations in the rooting basal medium of Nothofagus nervosa. Significant variation in endogenous calcium concentrations was detected along the rooting phase, strongly correlated with rhizogenesis phenomenons and linked to total peroxidase variation as cited elsewhere. Calcium and boron concentrations in the basal medium significantly affected the rooting. Treatment containing 60 mg.L-1 Ca and 1 mg.L-1 B produced root formation in fewer days than other combinations. The variation of these nutrient concentrations in the medium is a useful tool to improve microcutting rooting. Roots are obtained earlier and in a shorter period of time, finally resulting in more homogeneous microplants with a better developed rooting system.

Boron↗
PubMed2001

Boron neutron capture therapy of brain tumors: investigation of urinary metabolites and oxidation products of sodium borocaptate by electrospray ionization mass spectrometry.

Boron neutron capture therapy (BNCT) is based on a nuclear capture reaction that occurs when boron-10, a stable isotope, is irradiated with low energy neutrons to produce high-energy alpha particles and recoiling lithium-7 nuclei. The purpose of the present study was to determine what urinary metabolites, if any, could be detected in patients with brain tumors who were given sodium borocaptate (BSH), a drug that has been used clinically for BNCT. BSH was infused intravenously over a 1-h time period at doses of 26.5, 44.1, or 88.2 mg/kg of body weight to patients with high-grade brain tumors. Electrospray ionization mass spectrometry has been used to investigate possible urinary metabolites of BSH. Chemical and instrument conditions were established to detect BSH and its possible metabolites in both positive and negative electrospray ionization modes. Using this methodology, boronated ions were found in patients' urine samples that appeared to be consistent with the following chemical structures: BSH sulfenic acid (BSOH), BSH sulfinic acid (BSO(2)H), BSH disulfide (BSSB), BSH thiosulfinate (BSOSB), and a BSH-S-cysteine conjugate (BSH-CYS). Although BSH has been used clinically for BNCT since the late 1960s, this is the first report of specific biotransformation products following administration to patients. Further studies will be required to determine both the biological significance of these metabolites and whether any of these accumulate in significant amounts in brain tumors.

Biotransformation↗
PubMed1992

Boron neutron capture therapy for murine malignant gliomas.

Boron neutron capture therapy (BNCT) involves administration of a boron compound followed by neutron irradiation of the target organ. The boron atom captures a neutron, which results in the release of densely ionizing helium and lithium ions that are highly damaging and usually lethal to cells within their combined track length of approximately 12 microns. Prior to Phase I clinical trials for patients with malignant gliomas, mice with glioma 261 intracerebral tumors were fed D,L-3-(p-boronophenyl)alanine and irradiated with total tumor doses of 1000-5000 RBE-cGy of single fraction thermal neutrons to determine the maximum tolerated dose and effect on survival. These mice were compared to mice that received D,L-3-(p-boronophenyl)alanine alone, neutron irradiation alone, photon irradiation alone, or no treatment. Additional normal mice received escalating doses of neutron irradiation to determine its toxicity to normal brain. BNCT caused a dose-dependent, statistically significant prolongation in survival at 1000-5000 RBE-cGy. At 3000 RBE-cGy, median survival rates of the BNCT and untreated control groups were 68 and 22 days, respectively, with a long-term survival rate of 33%. At 4000 RBE-cGy, median survival was 72 and 21 days, respectively, with a long-term survival rate of 43%. At lower radiation doses, the extended survival was comparable between the BNCT and photon-irradiated mice; however, at 3000 and 4000 RBE-cGy the median survival of BNCT-treated mice was significantly greater than photon-irradiated mice. The maximum tolerated single fraction dose to normal brain was approximately 2000 RBE-cGy.

Animals↗
PubMed2004

[Research advance in characteristics of molybdenum, boron and selenium in red soils of South China and effects of their reasonable application on forage grass growth].

Reasonable fertilization and fertility improvement of red soils are the important measures to develop the forage industry in hilly regions of South China. This paper summarized the existing form, chemical feature, availability and content of molybdenum, boron and selenium in red soils of South China. The lack of these three microelements in red soils was in common, and their reasonable application could significantly improve the growth of forage grass and its yield. The authors discussed the effects of molybdenum, boron and selenium application on the uptake and accumulation of available nutrients by forage grass and relevant physiological functions, described the molybdenum, boron and selenium deficiency symptoms of forage grass, their diagnostic methods and correcting measures, and put forward some suggestions for deepening the study.

Boron↗
PubMed2006

[Preparation and photocatalytic activity of boron doped CeO2/TiO2 mixed oxides].

Boron doped CeO2/TiO2 mixed oxides photocatalysts were prepared by adding boric acid and cerous nitrate during the hydrolyzation of titanium trichloride and tetrabutyl titanate. XRD, UV-Vis DRS and XPS techniques were used to characterize the crystalline structure, light absorbing ability and the chemical state of Boron element in the photocatalyst sample. The photocatalytic activities were evaluated by monitoring the degradation of acid red B under UV irradiation. These results indicate that the wavelengths at adsorbing edge are affected by the content of cerous nitrate and the maximum absorption wavelength is about 481 nm when the mole ratio of Ce/Ti is 1.0. For higher dosage of Cerium, the absorbance edge shifts to blue slightly. The prepared photocatalyst is composed of anatase TiO2 and cubic CeO2 when calcined at 500 degrees C. An increase in the calcination temperature transforms the crystalline structure of the titanium oxides from anatase to rutile, and has no obvious influence on crystalline structure of CeO2 but crystallites growth up. The absorbance edge decreases drastically with the increase of calcination temperature. With a view to the stability of photocatalyst and utilization of sun energy, 500 degrees C of calcination temperature is recommended. The XP spectrum for B1s exhibits that only a few boron ions dope into titania and ceria matrix, others exist in B2O3. The photocatalytic activity increases with increase of cerous nitrate dosage, and decreases drastically due to higher dosage (the mol ratio of Ce/Ti > 0.5). After 10 min UV irradiation, 96% of acid red B is degraded completely over photocatalyst under optimum reaction condition.

Boron↗
PubMedDate not supplied

Acute toxicity of boric acid and boron tissue residues after chronic exposure in broiler chickens.

The acute oral mean lethal dose of boric acid in 1-day-old chickens was found to be 2.95 +/- 0.35 g/kg of body weight, which classifies this product as only slightly toxic to chickens. One-day-old broiler chicks were housed in floor pens in which litter had been treated with 0, 0.9, 3.6, or 7.2 kg of boric acid per 9.9 m2 of floor space. Boron residue levels in brain, kidney, liver, and white muscle were not statistically elevated following a 15-day exposure period. Boron residue levels in the same types of tissue were not significantly elevated in chicks fed 500 ppm or 1250 ppm boric acid in feed ad libitum for 3 weeks; however, residues were significantly higher in chicks fed 2500 ppm or 5000 ppm boric acid. These data indicate that broilers grown on boric acid-treated litter do not consume enough boric acid to cause elevated boron levels in tissues.

Animal Feed↗
PubMed1989

The effects of boron hypolipidemic agents on LDL and HDL receptor binding and related enzyme activities of rat hepatocytes, aorta cells and human fibroblasts.

Two boron-containing hypolipidemic agents, N,N-dimethyl-n-octadecylamine borane and tetrakis-mu-(trimethylamine-boranecarboxylato)bis-(trimethylamine- carboxyborane)-dicopper(II) were shown to reduce significantly serum cholesterol and triglyceride levels after 14 days administration in rats. Serum low density lipoprotein (LDL) cholesterol content was reduced by both agents; however, high density lipoprotein (HDL) cholesterol was elevated by N,N-dimethyl-n-octadecylamine borane but reduced by the dicopper (II) complex. The boron agents suppressed LDL binding and internalization in hepatocytes, fibroblasts and aorta cells and elevated HDL binding and degradation in hepatocytes. Enzyme activities were modulated by the boron derivatives which would favor less cholesterol deposition in peripheral tissues and further clearance from the plaque cells.

Animals↗
PubMed1985

UV-absorbance profile of human leukocytic ultrafiltrate after affinity chromatography on immobilized m-aminophenyl boronic acid: implication for transfer factor purification.

The UV-absorbance of the lysed human leukocyte ultrafiltrate (LLU) was investigated by Sephadex G-15 gel permeation chromatography before and after affinity chromatography on immobilized m-aminophenyl boronic acid. This biospecific fractionation caused substantial changes in 260/280-nm absorbance ratio of individual peaks as revealed by Sephadex G-15 gel permeation chromatography. While the material which had passed through the affinity support unretarded (W) appeared to be partly or completely deprived of peak IV, peaks IV and V were fairly enriched in the retarded material (R). This material, on the other hand, nearly completely missed peaks III, VI and VII. Peak III was copiously represented in material W. Boronate affinity chromatography caused enrichment in the protein content as well as in the content of purine/pyrimidine-bound ribose of material R, i.e. cis-diol group containing (RNA-like) material, considered to represent functional transfer factor activity. The described findings further support the use of immobilized derivatives of boronic acid in the separation of coplanar cis-diol group containing compounds from other constituents of LLU.

Boronic Acids↗
PubMed1988

Boron neutron capture therapy of a murine melanoma.

Boron neutron capture therapy has been carried out on BALB/c mice carrying the Harding-Passey melanoma s.c. on the thigh. p-Boronophenylalanine (BPA), a boronated analogue of natural melanin precursors, was used to target boron selectively to melanoma. BPA was administered to the mice either via i.p. injection or p.o. by intubation. 10B concentrations in tumor ranged from 15 to 40 ppm depending on the route and timing of administration. Irradiations with a predominantly thermal neutron beam were performed at the Brookhaven Medical Research Reactor. In the absence of BPA, only transient tumor growth delays were observed at low neutron fluences. At 5 x 10(16) n/m2, 4 of 22 tumors irradiated in the absence of BPA underwent long-term tumor growth control; after p.o. administration of BPA (40 ppm 10B in the tumor), the fraction of tumors controlled increased to 11 of 19. The average dose to the tumor in the latter group was 17.8 Gy, of which 14.8 Gy were due to the 10B neutron capture reaction. The biological effectiveness of the absorbed dose from the neutron capture reaction, at the 50% tumor control level, was found to be twice that of 100 kVp X-rays.

Animals↗
PubMed1986

Boron distribution analysis by alpha-autoradiography.

The distribution of the boron-10 compound, Na2 10B12H11SH, which is now in clinical use for boron neutron capture therapy for brain tumors, was studied topographically and quantitatively in rats using neutron-induced alpha-autoradiography. Transplanted intracerebral tumors in Sprague-Dawley rats were used. In the normal brain, only a minute amount of 10B (less than 1 microgram 10B/cm3) was found in the brain parenchyma, except for the infundibulum and area postrema. Boron-10 accumulated in the brain tumors. The tumor-to-blood concentration ratio of 10B increased with time after injection and reached unity 12 hr after injection. The tumor concentration calculated at that time was 18 micrograms 10B/cm3. This study clearly shows that this 10B compound accumulates in the transplanted rat tumors in the brain and that tumor concentration and tumor-to-blood ratio of 10B can provide a sufficient condition for brain tumor treatment.

Animals↗