PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Boron Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

[The toxicokinetics of low-solubility substances (exemplified by 2 boron compounds)].

Multichamber toxicokinetic model studies of the resorption, distribution and excretion properties of poorly soluble substances in subchronic action of suspensions administered intragastrically can be the first step in prognosing the toxicokinetic properties of the inhaled aerosols of the substances mostly discharged from the respiratory into the gastrointestinal tract (GIT). The generally accepted quantitative characteristics of the particles' deposition and translocation into GIT can provide a further application of the model for a mathematical description of a prolonged inhalational exposure to some substances. This technique was tested with the boron compounds characterized by low solubility and revealed a good correlation between the prognosed and actual deposits of the substance in the organ and excretions. At the same time, detected were some qualitative and quantitative differences in the boron toxicokinetics influenced by magnesium deboride and hexaborate, which were explained by differences in their solubility.

Air Pollutants, Occupational↗
PubMed1992

Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumors.

Borocaptate sodium (Na2B12H11SH) is a boron-carrying compound under consideration for use in boron neutron capture therapy. The biodistribution of boron from borocaptate sodium administration will partly determine boron neutron capture therapy efficacy and normal tissue radiation tolerance. The biodistribution of boron was determined in 30 dogs with spontaneous intracranial tumors at 2, 6, or 12 hr after intravenous borocaptate sodium infusion. Blood and tissue boron concentrations were measured using inductively coupled plasma atomic emission spectroscopy. Mean tumor boron concentration (mean +/- standard error) was 35.9 +/- 4.6 (n = 15), 22.5 +/- 6.0 (n = 9), and 7.0 +/- 1.1 micrograms of boron per g (n = 6) at 2, 6, and 12 hr, respectively, after borocaptate sodium infusion. Peritumor boron concentrations were elevated above that of normal brain in half of the dogs. Normal brain boron concentration (mean +/- standard error) was 4.0 +/- 0.5, 2.0 +/- 0.4, and 2.0 +/- 0.3 micrograms of boron per g at 2, 6, and 12 hr after infusion, respectively. Some cranial and systemic tissues, and blood, had high boron concentration relative to tumor tissue. Geometric dose sparing should partly offset these relatively high normal tissue and blood concentrations. Borocaptate sodium biodistribution is favorable because tumor boron concentrations of recommended magnitude for boron neutron capture therapy were obtained and there was a high tumor-to-normal brain boron concentration ratio.

Animals↗
PubMed1991

4-Borono-2-[18F]fluoro-D,L-phenylalanine as a target compound for boron neutron capture therapy: tumor imaging potential with positron emission tomography.

We studied the tumor uptake and metabolism of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), an 18F-labeled target compound for boron neutron capture therapy. In mice bearing FM3A mammary carcinoma, the accumulation of [18F]FBPA in the FM3A for the first 2 h, and its decrease in all other tissues, resulted in high FM3A-to-tissue uptake ratios. In the FM3A, the tracer was stable for metabolic alteration, which was in contrast to the gradual increase of protein-bound radioactivity in plasma. Imaging of FM3A was demonstrated by whole body autoradiography. [18F]FBPA has potential for use as a PET tracer for tumor imaging with high contrast, even in the pancreas.

Animals↗
PubMed1992

Present status of boron neutron capture therapy.

The neutron capture reaction 10B(1n,4He)7Li produces two energetic particles, 4He2+ and 7Li3+ that are strongly cell toxic. Due to the short range of these nuclear fragments (5-9 microns) mainly those cells that have bound or internalized a 10B-containing substance are growth-inactivated. The most critical and difficult step in an efficient boron neutron capture therapy (BNCT) is the tumour targeting. It is today possible to synthesize a large number of boron compounds and conjugate them to tumour-seeking macromolecules, such as monoclonal antibodies or different polypeptides. The boron-containing substances presently considered for therapy are sulfhydryl boron hydride (BSH) and boron-phenylalanine, (BPA) for the treatment of gliomas and malignant melanomas respectively. Other boronated compounds considered are ligands for receptor-amplified tumour cells, antibodies for tumour cells with specific antigens and thioureas for treatment of melanotic melanomas. The required boron concentration is given by the relative dose due to neutron capture in 10B and that of the competing capture reactions in nitrogen and hydrogen. Capture in nitrogen produces protons with a range of about 10-11 microns and this gives a radiation dose to all cells in the neutron activated area. Calculations show that the local concentration of 10B near the critical radiation target, DNA, must be higher than 10 ppm (10 micrograms/g). Increased emphasis will be put on the development of combinations of treatments that fulfil the requirements for attacking the microscopic spread of the tumour.

Boron↗
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↗
PubMed1992

Boron neutron capture therapy for cancer. Realities and prospects.

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10 (10B), is irradiated with low-energy thermal neutrons (nth) to yield (4He) alpha-particles and 7Li nuclei (10B+nth-->[11B]-->4He+7Li+2.31 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. The current review covered the radiobiologic considerations on which BNCT is based, including a brief discussion of microdosimetry and normal tissue tolerance. The development of tumor-localizing boron compounds was discussed, including the sulfhydryl-containing polyhedral borane, sodium borocaptate (Na2B12H11SH), and boronophenylalanine (BPA), both of which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Compounds currently under evaluation, such as boronated porphyrins, nucleosides, liposomes, and monoclonal antibodies (MoAbs), were also considered. Nuclear reactors have been used as the exclusive source of neutrons for BNCT. The use of low-energy (0.025 eV) thermal neutrons and higher-energy (1-10,000 eV) epithermal beams, beam optimization, and possible alternative neutron sources (accelerators) were also discussed. Clinical studies performed in the United States during the 1950s and 1960s for the treatment of malignant brain tumors were reviewed. Current studies in Japan and future studies in Europe and the United States concerning the treatment of glioblastomas and melanomas by BNCT were discussed, as were critical issues that must be addressed if BNCT is ever to be a useful therapeutic modality.

Boron Neutron Capture Therapy↗
PubMed1992

Boron neutron capture therapy of anterior chamber melanoma with p-boronophenylalanine.

Boron neutron capture therapy (BNCT) is a form of radiation therapy that requires selective uptake of boron by the tumor and irradiation with thermal neutrons. Phenylalanine is an amino acid precursor of melanin and when boronated (p-boronophenylalanine [BPA]) was found to be selectively taken up by Greene melanoma cells in the anterior chamber of rabbits. This tumor model was irradiated 24 hr after oral administration of BPA and was used for biodistribution studies that compared BPA and sodium pentaborate. Three groups were irradiated: group 1 (11 rabbits) received BPA followed by thermal neutron irradiation, group 2 (9 rabbits) received thermal neutron irradiation only, and group 3 (9 rabbits) served as unirradiated, undrugged control animals. Eight of the 11 tumors in group 1 were treated successfully; all tumors in groups 2 and 3 grew. Histopathologic examination did not reveal vascular or retina damage in group 1. These preliminary experiments confirm that newer boronated compounds, such as BPA, used in BNCT and improved neutron beams can provide selective irradiation of ocular melanomas.

Administration, Oral↗
PubMed1977

Cataractogenic effects of a boron hydride disulfide compound.

The disulfide form but not the sulfhydryl form of a boron hydride compound was found to be cataractogenic. Apparently this compound attaches to the sulfhydryl group of Na-K ATPase in the lens epithelium inactivating this crucial enzyme. The consequence is that a defect in the cation pump activity arises, leading to a rapid influx of Na ions and loss of K ions and marked increase in hydration. These changes are thought to lead to opacification.

Acute Disease↗
PubMed1991

Biological efficacy of boronated low-density lipoprotein for boron neutron capture therapy as measured in cell culture.

Low-density lipoproteins (LDLs) are known to be internalized by the cell through receptor-mediated mechanisms. There is evidence that LDLs may be taken up avidly by tumor cells to provide cholesterol for the synthesis of cell membranes. Thus, the possibility exists that LDLs may provide an ideal vehicle for the transport of boron to tumor cells for boron neutron capture therapy. A boronated analogue of LDL has recently been synthesized for possible application in boron neutron capture therapy. The analogue was tested in cell culture for uptake and biological efficacy in the thermal neutron beam at the Brookhaven Medical Research Reactor. It was found that boron concentrations 10 times higher than that required in tumors for boron neutron capture therapy were easily obtained and that the amount of uptake was consistent with a receptor-mediated binding mechanism. The measured intracellular concentration of approximately 240 micrograms 10B/g cells is significantly higher than that obtained with any other boron compound previously evaluated for possible clinical application.

Animals↗
PubMed1990

Immunoreactivity of boronated antibodies.

Boronated antibodies have already been evaluated as agents in neutron capture therapy. Because the boronation procedure may alter the properties of the antibody it is important to study the immunoreactivity of the conjugated antibody before in vivo use. In our studies of two dextran-boronated monoclonal antibodies, anti-glial fibrillary acidic protein antibody, and anti-hyaluronectin antibody, we have used ELISA and immunohistological methods to determine antibody activity and specificity. A ten-fold decrease in activity was observed for both antibodies in ELISA, and non-specific interactions were seen in both immunohistological and ELISA procedures. The boron compound used was shown to be at least partly responsible for these non-specific interactions.

Animals↗
PubMed1992

Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes.

The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective concentration of boron-10 within malignant tumors. The potential of liposomes to deliver boron-rich compounds to tumors has been assessed by the examination of the biodistribution of boron delivered by liposomes in tumor-bearing mice. Small unilamellar vesicles with mean diameters of 70 nm or less, composed of a pure synthetic phospholipid (distearoyl phosphatidylcholine) and cholesterol, have been found to stably encapsulate high concentrations of water-soluble ionic boron compounds. The hydrolytically stable borane anions B10H10(2-), B12H11SH2-, B20H17OH4-, B20H19(3-), and the normal form and photoisomer of B20H18(2-) were encapsulated in liposomes as their soluble sodium salts. The tissue concentration of boron in tumor-bearing mice was measured at several time points over 48 h after i.v. injection of emulsions of liposomes containing the borane anions. Although the boron compounds used do not exhibit an affinity for tumors and are normally rapidly cleared from the body, liposomes were observed to selectively deliver the borane anions to tumors. The highest tumor concentrations achieved reached the therapeutic range (greater than 15 micrograms of boron per g of tumor) while maintaining high tumor-boron/blood-boron ratios (greater than 3). The most favorable results were obtained with the two isomers of B20H18(2-). These boron compounds have the capability to react with intracellular components after they have been deposited within tumor cells by the liposome, thereby preventing the borane ion from being released into blood.

Animals↗
PubMed1992

4-Borono-2-[18F]fluoro-D,L-phenylalanine: a possible tracer for melanoma diagnosis with PET.

The potential of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), a flurodinated derivative of a target compound for boron neutron capture therapy, for melanoma imaging by positron emission tomography (PET) was studied using animal models. A high uptake of [18F]FBPA was found in murine B16 melanoma or in Greene's melanoma No. 179, a melanotic cell line in hamsters, for the first 6 h after injection. Whole body autoradiography using [18F]FBPA gave a clear image of the B16 tumor. The acid-insoluble 18F in the B16 increased to 27% by 6 h, and most of the free 18F was detected as [18F]FBPA in both B16 and plasma. In the hamster models, No. 179 showed a 1.7 times higher uptake than amelanotic Greene's melanoma No. 178 at 6 h post-injection, although both melanomas indicated similar metabolic activities when examined by a tracer uptake study using L-[14C]methionine, 2-deoxy-D-[14C]glucose and [3H]thymidine. [18F]FBPA may be a very promising PET tracer for melanoma imaging.

Animals↗
PubMed1991

Synthesis and radiation dosimetry of 4-borono-2-[18F]fluoro-D,L-phenylalanine: a target compound for PET and boron neutron capture therapy.

The 18F-labeling of 4-borono-D-L-phenylalanine (BPA), a potential target compound for cancer treatment with boron neutron capture therapy, is described. By direct fluorination of BPA with [18F]AcOF or [18F]F2 followed by HPLC separation, 4-borono-2-[18F]fluoro-D,L-phenylalanine was prepared with radiochemical yields of 25-35% and with a radiochemical purity of over 99%. The tissue distribution study showed that the compound has potential as a tracer for pancreas imaging with positron emission tomography. Radiation dosimetry is also described.

Animals↗
PubMed1992

A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2-[18F]fluoro-L-phenylalanine.

A unique in vivo approach to assessing the concentrations of 4-[10B]borono-L-phenylalanine (L-BPA), a melanoma targeting compound for boron neutron capture therapy (BNCT), was investigated using L-BPA labelled with positron-emitting 18F (half-life = 110 min), i.e., 4-[10B]borono-2-[18F]fluoro-L-phenylalanine (L-[18F]FBPA). High melanoma uptake of L-[18F]FBPA was reduced slightly by competition with L-BPA in the two animal models of the murine B16 melanoma and the melanotic Greene's melanoma No. 179 in hamsters. In mice given L-[18F]FBPA and L-BPA, the concentrations of 10B in B16 estimated from 18F radioactivity were lower than those measured by inductively coupled plasma-atomic emission spectroscopy. Lower estimated values were dependent on the time after injection and on the loading dose of L-BPA. The estimated 10B concentrations for Green's melanomas were comparable to the measured values. Positron emission tomography (PET) using L-[18F]FBPA allowed Greene's melanomas to be clearly visualized. In conclusion, when L-[18F]FBPA is used as a probe for L-BPA in BNCT of malignant melanomas, the melanoma can be localized and the 10B concentrations in tissues can be assessed in vivo using 18F radioactivity by PET.

Animals↗