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At least 1,063 records · Page 59Linked to original sources
PubMed2006

Well-orientated cubic boron nitride nanocrystals as studied by high-resolution transmission electron microscopy.

In a boron nitride thin film, grown on a Si (100) substrate by radio frequency magnetron sputtering, a striking nanostructure is observed by high-resolution transmission electron microscopy. It consists of cubic boron nitride nanocrystals with a rather good triangular shape, pointing always to the substrate. The nanocrystals are usually highly defected and present their own interesting internal structure. Texture formation is observed within a nanocrystal, with all the subgrains observed to have a common <011> axis, which is also approximately parallel to a <011> axis of the Si substrate, i.e. the nanocrystals are very well structurally orientated in relation to the Si substrate (self-organized). Dislocations and stacking faults are also found in the nanocrystals.

Journal Article↗
PubMed2003

Shock-induced localized amorphization in boron carbide.

High-resolution electron microscope observations of shock-loaded boron carbide have revealed the formation of nanoscale intragranular amorphous bands that occur parallel to specific crystallographic planes and contiguously with apparent cleaved fracture surfaces. This damage mechanism explains the measured, but not previously understood, decrease in the ballistic performance of boron carbide at high impact rates and pressures. The formation of these amorphous bands is also an example of how shock loading can result in the synthesis of novel structures and materials with substantially altered properties.

Journal Article↗
PubMed2005

High-order harmonic generation from boron plasma in the extreme-ultraviolet range.

We demonstrate the generation of up to the 63rd harmonic (lambda = 12.6 nm) of a Ti:sapphire laser pulse (150 fs, 10 mJ), using a prepulse- (210-ps,24-mJ) produced boron plasma as the nonlinear medium. The influence of various parameters on the harmonic conversion efficiency was analyzed. The steep decrease in intensity for low-order harmonics (up to 19th order) was followed by a plateau. Typical conversion efficiencies were evaluated to be 10(-4) (for a 3rd harmonic) to 10(-7) (within the plateau region). Harmonic generation appeared to be efficient for the plasma that comprised neutral atoms and singly ionized boron.

Journal Article↗
PubMed2006

Design of a rotating facility for extracorporal treatment of an explanted liver with disseminated metastases by boron neutron capture therapy with an epithermal neutron beam.

In 2001, at the TRIGA reactor of the University of Pavia (Italy), a patient suffering from diffuse liver metastases from an adenocarcinoma of the sigmoid was successfully treated by boron neutron capture therapy (BNCT). The procedure involved boron infusion prior to hepatectomy, irradiation of the explanted liver at the thermal column of the reactor, and subsequent reimplantation. A complete response was observed. This encouraging outcome stimulated the Essen/Petten BNCT group to investigate whether such an extracorporal irradiation could be performed at the BNCT irradiation facility at the HFR Petten (The Netherlands), which has very different irradiation characteristics than the Pavia facility. A computational study has been carried out. A rotating PMMA container with a liver, surrounded by PMMA and graphite, is simulated using the Monte Carlo code MCNP. Due to the rotation and neutron moderation of the PMMA container, the initial epithermal neutron beam provides a nearly homogeneous thermal neutron field in the liver. The main conditions for treatment as reported from the Pavia experiment, i.e. a thermal neutron fluence of 4 x 10(12) +/- 20% cm(-2), can be closely met at the HFR in an acceptable time, which, depending on the defined conditions, is between 140 and 180 min.

Computer Simulation↗
PubMedDate not supplied

Boron neutron capture therapy of brain tumors: clinical trials at the finnish facility using boronophenylalanine.

Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400 mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61 Gy (W), and the average normal brain dose from 3 to 6 Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50-60 Gy, were treated with BPA-based BNCT using the BPA dosage of 290 mg/kg. The average planning target dose in these patients was 25-29 Gy (W), and the average whole brain dose 2-3 Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photon radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.

Adult↗
PubMed1994

Response of the central nervous system to boron neutron capture irradiation: evaluation using rat spinal cord model.

The response of the central nervous system to boron neutron capture irradiation, with either p-boronophenylalanine (BPA) or borocaptate sodium (BSH) as neutron capture agents, has been assessed using a rat spinal cord model. The mean latency times for the development of myelopathy after irradiation with the thermal neutron beam-alone, or in combination with BPA or BSH, were 23.7 +/- 0.3, 21.8 +/- 0.4 and 19.6 +/- 0.4 weeks, respectively. The radiation-induced lesion in the spinal cord was characterised by white matter necrosis. Due to the variations in the microdistribution of different neutron capture agents in body tissues, it was considered inappropriate to define the biological effectiveness of the high LET radiation, resulting from the 10B(n, alpha)7Li neutron capture reaction, relative to photon radiation, using the term 'relative biological effectiveness' (RBE). The term 'compound biological effectiveness' (CBE) factor was used as an alternative. ED50 values for the various irradiation modalities were calculated from probit fitted dose effect curves. Expressed as total physical absorbed doses these values were 13.6 +/- 0.4, 30.3 +/- 2.7 and 13.8 +/- 0.5 Gy after irradiation with the thermal neutron beam alone, or the thermal neutron beam in combination with BSH or BPA, respectively. The RBE of the thermal neutron beam was 1.4 +/- 0.04. The microdistribution of the two neutron capture agents played a crucial role in the determination of the overall biological effect, after thermal neutron activation. BSH, which is excluded from the CNS parenchyma by the blood brain barrier, had a low CBE factor value of 0.46 +/- 0.5. BPA, on the other hand, which crosses the blood brain barrier and distributes in the CNS parenchyma, had a higher CBE factor value of 1.33 +/- 0.16.

Absorption↗
PubMed1997

Synthesis of carboranes containing an azulene framework and in vitro evaluation as boron carriers.

3-(o-Carboranylhydroxymethyl)-7-isopropylazulene sodium carboxylate (1) and 3-(o-carboranylmethyl)-7-isopropylazulene sodium sulfonate (2) were synthesized from the palladium-catalyzed addition reaction of 1-carboranyltributylstannane (4) to azulene aldehydes (3 and 9). Although the water solubility of 1 was of the order of 10(-6) M, that of 2 was of the order of 10(-3) M and was enough for clinical use. The cytotoxicity of 1 (IC50) toward B-16 melanoma cells was of the order of 10(-5) M, whereas that of 2 was of the order of 10(-4) M. This value was close to that of BPA (approximately 9 x 10(-3) M) which is utilized for clinical use. The boron uptake by B-16 cells was 0.17 microgram of B/10(6) cells for 1 and 0.25 microgram of B/10(6) cells for 2. It is clear that compound 2 accumulates in B-16 melanoma cells with a significantly high level although it is highly water soluble and its cytotoxicity is significantly low.

Animals↗
PubMed2006

Multi-nuclear MRS and 19F MRI of 19F-labelled and 10B-enriched p-boronophenylalanine-fructose complex to optimize boron neutron capture therapy: phantom studies at high magnetic fields.

Reaction yield optimization for the synthesis and the complexation of a boron neutron capture therapy agent (19)F-labelled, (10)B-enriched p-boronophenylalanine-fructose ((19)F-BPA-fr) complex was obtained. (1)H, (19)F, (13)C and (10)B magnetic resonance spectroscopy (MRS) of the (19)F-BPA-fr complex in aqueous and rat blood solution phantoms and its spatial distribution mapping using (19)F magnetic resonance imaging (MRI) results are reported. 7 T and 9.4 T magnetic fields were used to perform MRI and MRS respectively. Our in vitro results suggest that in vivo studies on (19)F-BPA through (19)F NMR will be feasible.

Animals↗
PubMed1995

Effect of L-10B-p-boronophenylalanine-fructose and the boron neutron capture reaction on mouse brain dopaminergic neurons.

Radiation damage to the dopamine tracts caused by enriched L-10B-p-boronophenylalanine (L-10BPA)-fructose and the boron neutron capture reaction was investigated using the mouse model. Following various treatments with L-10BPA and neutron irradiation of the head, the brain was perfusion fixed and removed; 50-microns frozen sections were cut. Dopaminergic neurons were visualized using immunohistochemistry for tyrosine hydroxylase. The administration of L-10BPA had no permanent effect on dopaminergic tracts. Neutron capture therapy with L-10BPA caused a reduction in tyrosine hydroxylase immunohistochemical activity within 4 h of irradiation, but by 48 h, this reduction reversed. No damage was observed at 120 h postirradiation.

Animals↗
PubMed1993

Boron neutron capture therapy of intracerebral melanoma using boronophenylalanine as a capture agent.

A rat brain tumor model has been developed utilizing nude rats and the human melanoma cell line MRA 27. For pharmacokinetic and tissue distribution studies, 2 10(5) MRA 27 cells were implanted intracerebrally (i.c.), and 30 days later, 120 mg of 10B-enriched L-boronophenylalanine were injected i.p. into nude rats. 10B concentrations in the tumor, blood, and normal brain were 23.7, 9.4, and 8.4 micrograms/g, respectively, 6 h following administration. For therapy experiments, tumor bearing rats were irradiated at the Brookhaven Medical Research Reactor 30 days following implantation. The median survival time was 44 days for untreated rats, 76 days for those receiving a physical dose of 2.7 Gy, and 93 days for those receiving 3.6 Gy. Animals receiving both 10B-L-boronophenylalanine and physical doses of 1.8, 2.7, or 3.6 Gy (total tumor physical doses of 5.0, 7.5, or 10.1 Gy) had median survival times of 170, 182, and 262 days, respectively. Forty % of rats that received the highest tumor dose (10.1 Gy) survived > 300 days. In a replicate experiment 21% of animals that had received L-boronophenylalanine and irradiation (total tumor physical dose of 10.1 Gy) were alive 220 days after therapy. In a parallel study, animals that were irradiated with gamma photons from a 137Cs source with 12 Gy or 2.0 Gy 9 delivered to the head had median survival times of 86 and 79 days, respectively, compared to 47 days for untreated animals. Our results indicate that boron neutron capture therapy is effective against i.c. melanoma in a rodent model and suggest that large animal studies are warranted to further assess its efficacy.

Animals↗
PubMed1998

Positron emission tomography-based boron neutron capture therapy using boronophenylalanine for high-grade gliomas: part II.

Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.

Boron↗
PubMed2000

Preparation of a new carboranyl lactoside for the treatment of cancer by boron neutron capture therapy: synthesis and toxicity of fluoro carboranyl glycosides for in vivo 19F-NMR spectroscopy.

The synthesis of new ortho-carboranyl lactosides 8, 17, 19 and glucosides 22 and 23 for the use in boron neutron capture therapy is reported. Carboranyl lactosides 17 and 19 as well as the glucosides 22 and 23 contain a fluorine atom to allow a noninvasive determination of these compounds in tumor cells by 19F-NMR spectroscopy. In cloning efficiency tests on human bronchial carcinoma cells the carboranyl lactosides 17 and 19 displayed almost no cytotoxicity. Thus, the considerably cytotoxic carboranyl alcohol 11 is detoxified when linked to a sugar moiety such as in carboranyl glucoside 22.

Antineoplastic Agents↗
PubMedDate not supplied

Boronated metalloporphyrins: a novel approach to the diagnosis and treatment of cancer using contrast-enhanced MR imaging and neutron capture therapy.

Porphyrins are a unique class of metal chelating agents that have shown specific affinity for neoplasms. The water-soluble free-base derivative, tetrakiscarborane carboxylate ester of 2,4-(alpha,beta-dihydroxyethyl) deuteroporphyrin IX (BOPP), an agent designed for neutron capture therapy, has previously demonstrated selective localization and retention in a C6 murine glioma. In the present work, the authors demonstrate that the manganese chelate of BOPP also selectively localizes in a rat 9L gliosarcoma and preferentially enhances the tumor-normal brain contrast of T1-weighted images for at least 92 hours. The data indicate a maximal enhancement of contrast between tumor and normal brain at 24 hours after injection, compared with 5 minutes for manganese (III) tetraphenylporphine sulfonate (TPPS4). The results also indicate that Mn-BOPP may have a slower uptake in the 9L glioma than Mn-TPPS4 but a longer retention in the tumor. Mn-BOPP is unique in that it represents, to the authors' knowledge, the first example of a single agent that can enhance contrast between tumor and normal tissue and be potentially effective as an agent for boron neutron capture therapy.

Animals↗
PubMed2006

Evaluation of hypoxia-specific cytotoxic bioreductive agent-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy.

PURPOSE: To evaluate the usefulness of 5 new 10B-compounds (TX-2091, TX-2095, TX-2097, TX-2100, and TX-2110) as 10B-carriers in boron neutron capture therpy (BNCT). They were conjugates that had been synthesized from a hypoxia-specific cytotoxic bioreductive agent, quinoxaline oxide TX-402, and a clinically used 10B-carrier, sodium borocaptate-10B (BSH). MATERIALS AND METHODS: The 5 new compounds were hybrid compounds that have both a hypoxic cytotoxin unit and a thermal neutron-sensitizing unit, BSH. These new compounds and BSH were administered intraperitoneally to SCC VII tumor-bearing mice. Then, the 10B concentrations in the tumors and normal tissues were measured by gamma-ray spectrometry. Subsequently, SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with TX-2100, which was chosen based on the results of the above-mentioned biodistribution analyses, or BSH in the same manner as in the biodistribution studies. Right after irradiation, during which intratumor 10B concentrations were kept at levels similar to each other, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling [= quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in the total (P+Q) tumor cell population was determined from the tumors that were not pretreated with BrdU. Clonogenic cell survival was also determined in mice given no BrdU. RESULTS: 10B biodistribution analyses in tumors, brain, skin, muscles, blood, and liver indicated that TX-2100 has the most favorable characteristics for concentrating a sufficient amount of 10B in tumors and maintaining a high enough 10B concentration during irradiation. In addition, TX-2100 had a significantly stronger radio-sensitizing effect with reactor thermal neutron beams than BSH on both total and Q cells in solid tumors. Further, TX-2100 clearly exhibited a radio-sensitizing effect with gamma-rays not only on total cells but also on Q and hypoxic tumor cells, which was not achieved by BSH. CONCLUSION: A 10B-carrier that acts as a hypoxic cytotoxin on tumor cells as well as having the potential to keep 10B in tumors and sensitize tumor cells more markedly than conventional 10B-carriers, such as TX-2100, is a promising candidate for use in BNCT.

Animals↗
PubMedDate not supplied

The use of positron emission tomography to develop boron neutron capture therapy treatment plans for metastatic malignant melanoma.

Centers in Japan and the United States are extending boron neutron capture therapy (BNCT) to the treatment of malignant melanoma (MM). Positron emission tomography (PET) has been used to image glioblastoma multiforme with 18F-boronophenylalanine (18F-BPA) for the purpose of generating 10B distribution maps. These distribution maps can be used to improve the BNCT treatment planning. 18F-BPA was given to a patient with widely metastatic MM involving the thorax and brain. 18F-BPA PET scans of the chest and the head were obtained and compared to the computed tomograms (CT) and magnetic resonance (MR) images. The lung metastases seen on the chest CT images and intracranial metastases seen on CT and MR images were correlated with the PET images. The PET images clearly identified a brain lesion that was difficult to identify on MR and CT images. The 18F-BPA lung and peri-oral mucous gland activity was intense indicating a relatively high concentration of BPA. The intensity seen in the peri-oral mucous glands is consistent with the experiences in the BNCT clinical trials. These results have implications in the use of BNCT outside of the cranium. The PET images allow the generation of treatment plans that are consistent with the clinical findings. PET imaging with 18F-BPA can be used to identify potential tumors that may be amenable to BNCT and to improve treatment plans prior to BNCT.

Boron Compounds↗
PubMedDate not supplied

Common challenges and problems in clinical trials of boron neutron capture therapy of brain tumors.

Clinical trials for binary therapies, like boron neutron capture therapy (BNCT), pose a number of unique problems and challenges in design, performance, and interpretation of results. In neutron beam development, different groups use different optimization parameters, resulting in beams being considerably different from each other. The design, development, testing, execution of patient pharmacokinetics and the evaluation of results from these studies differ widely. Finally, the clinical trials involving patient treatments vary in many aspects such as their dose escalation strategies, treatment planning methodologies, and the reporting of data. The implications of these differences in the data accrued from these trials are discussed. The BNCT community needs to standardize each aspect of the design, implementation, and reporting of clinical trials so that the data can be used meaningfully.

Boron Compounds↗
PubMed2003

Boron neutron capture therapy (BNCT) for malignant melanoma with special reference to absorbed doses to the normal skin and tumor.

Twenty-two patients with malignant melanoma were treated with boron neutron capture therapy (BNCT) using 10B-p-boronophenylalanine (BPA). The estimation of absorbed dose and optimization of treatment dose based on the pharmacokinetics of BPA in melanoma patients is described. The doses of gamma-rays were measured using small TLDs of Mg2SiO4 (Tb) and thermal neutron fluence was measured using gold foil and wire. The total absorbed dose to the tissue from BNCT was obtained by summing the primary and capture gamma-ray doses and the high LET radiation doses from 10B(n, alpha)7Li and 14N(n,p)14C reactions. The key point of the dose optimization is that the skin surrounding the tumour is always irradiated to 18 Gy-Eq, which is the maximum tolerable dose to the skin, regardless of the 10B-concentration in the tumor. The neutron fluence was optimized as follows. (1) The 10B concentration in the blood was measured 15-40 min after the start of neutron irradiation. (2) The 10B-concentration in the skin was estimated by multiplying the blood 10B value by a factor of 1.3. (3) The neutron fluence was calculated. Absorbed doses to the skin ranged from 15.7 to 37.1 Gy-Eq. Among the patients, 16 out of 22 patients exhibited tolerable skin damage. Although six patients showed skin damage that exceeded the tolerance level, three of them could be cured within a few months after BNCT and the remaining three developed severe skin damage requiring skin grafts. The absorbed doses to the tumor ranged from 15.7 to 68.5 Gy-Eq and the percentage of complete response was 73% (16/22). When BNCT is used in the treatment of malignant melanoma, based on the pharmacokinetics of BPA and radiobiological considerations, promising clinical results have been obtained, although many problems and issues remain to be solved.

Aged↗
PubMed2000

Pharmacokinetics and effects after intravenous administration of high-dose boron to rat.

Boron (B) compounds have been widely used in the chemical industry, agriculture, and environmental science. The kinetics and toxicity of B were studied by analyzing several serum and urine parameters after a single intravenous injection of sodium tetraborate solution (B: 85.7 mg/kg) in Wistar male rats. Blood samples were removed at 0, 1, 2, 4, and 6 h after injection. The serum parameters studied included: B, Na, Ca, K, P, Mg, gamma-GTP, AST, ALT, BUN, Cr, CK, LDH and ALD. Plasma concentration-time profiles of B were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Urine samples were collected from the bladder following infusion. The urinary parameters that were studied included urine volume and excretion of B, Cr and NAG. Results indicated that a two-compartment model could describe the elimination of B from plasma after intravenous administration. Urine volume significantly increased. A diuretic effect of B was noted.

Analysis of Variance↗