PubMed Health⌕ Search

Biomedical subjects

A H Soloway

Publications and source records attributed to A H Soloway.

At least 19 recordsLinked to original sources
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

Synthesis and in vitro evaluation of boronated uridine and glucose derivatives for boron neutron capture therapy.

The following boron-containing nucleoside and glucose derivatives have been synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT): 2'-O-(o-carboran-1-ylmethyl)uridine (4a), 3'-O-(o-carboran-1-ylmethyl)uridine (4b), sodium 7-(uridin-2'-ylmethyl)dodecahydro-7,8-dicarba-++ +nido-undecaborate (5), 5'-O-(o-carboran-1-ylmethyl)uridine (9), and 3'-O-(o-carboran-1-ylmethyl)-D-glucose (13). In vitro cellular uptake studies were performed with F98 rat glioma cells. Following 16 h incubation, cellular boron concentrations were determined by direct current plasma atomic emission spectroscopy (DCP-AES). Boron concentrations ranged from 65 to 103 micrograms/g of cells for the neutral closo structures compared with 1.5 micrograms/g of cells for the charged nido species. Cellular uptake of sodium mercaptoundecahydro-closo-dodecaborate (BSH), the compound currently being used in Japan for the treatment of malignant brain tumors by BNCT, was 2 micrograms/g of cells.

Animals↗
PubMed1991

Determination of boron in tissues and cells using direct-current plasma atomic emission spectroscopy.

We have developed a safe, simple, and efficient method for boron determination by means of direct-current plasma atomic emission spectroscopy. Tissues were solubilized by using concentrated sulfuric acid and 70% hydrogen peroxide to digest the samples without the need of high temperatures and pressures. Boron cluster compounds could be measured with sensitivity, precision, and accuracy similar to those of boric acid standards. Results obtained with [(C2H5)3NH]2B12H12, Cs2B12H11SH.H2O, and C15H32B10O6 show that this analytical method is applicable to a variety of compounds with different chemical structures. A sensitivity of 0.1 ppm has been obtained with known standards alone and in a variety of tissue matrices including tumor, blood, liver, skin, and cell suspensions. The measurement of total boron by direct-current plasma atomic emission spectroscopy (DCP-AES) has been achieved with as little as 50 mg of tissue or as few as 5 x 10(7) cells. The procedure is applicable to the analysis of boron in the ppm range with a high degree of precision and accuracy.

Animals↗
PubMed1990

Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy.

This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity.

Animals↗
PubMed1989

Pre-clinical studies on boron neutron capture therapy.

The present report provides an overview of the multidisciplinary research effort on BNCT that currently is in progress at The Ohio State University. Areas under investigation include the preparation of boron containing monoclonal antibodies, the synthesis of boron containing derivatives of promazines and phathalocyanines, the development of a rat model for the treatment of glioblastoma by means of BNCT, the design of an accelerator-based neutron irradiation facility, and 10B concentration measurements using alpha track autoradiographic methods. Progress in each of these areas is described and the direction of future research is indicated.

Animals↗
PubMed1989

Boron neutron capture therapy: linkage of a boronated macromolecule to monoclonal antibodies directed against tumor-associated antigens.

Two new protein-binding polyhedral boron derivatives, isocyanatoundecahydro-closo-dodecaborate(2-) (1) and isocyanato(trimethylamino)octahydro-closo-decaborate(1 -) (2), were synthesized. These anionic isocyanates have long hydrolysis half-lives at pH 7 and react readily with primary or secondary aliphatic amines resulting in spontaneous urea linkage. Utilizing 1, 1100 boron atoms (7.3% boron by weight) were incorporated per molecule of a polyclonal antibody directed against human thymocytes (anti-thymocyte globulin) without denaturation. However, immunoreactivity of the conjugates was lost. Reaction of 1 and 2 with polylysine yielded boronated macromolecules containing 21-28% boron by weight (up to 2000 boron atoms per molecule). Polylysine boronated with 2 was successfully linked to antibody molecules employing the heterobifunctional linking molecules N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) and m-maleimidobenzoyl sulfosuccinimide ester (sulfo-MBS). Separation of the conjugated antibody from the free boronated macromolecules and unconjugated antibody molecules has been achieved by gel filtration on a Sephacryl S-300 column. By linking boronated polylysine to antibodies, greater than 10(3) boron atoms were incorporated with the attachment of this species to one or more sites on the antibody molecule. The resulting immunoconjugates contained greater than 10(3) boron atoms per molecule, retained their immunoreactivity, and potentially might be useful for the selective delivery of large numbers of boron atoms to tumor cells.

Animals↗
PubMed1989

Ultrastructural microvascular response to boron neutron capture therapy in an experimental model.

A CD 344 rat glioma model currently used to investigate boron neutron capture therapy (BNCT) was used to demonstrate an increased survival rate after thermal neutron irradiation enhanced by administration of 10B-enriched polyhedral borane, Na2B12H11SH. To investigate the possible effects of BNCT on normal and tumor microvasculature, we subjected animals to sublethal neutron irradiation with and without intravenous injection of 50 mg/kg of enriched 10B and performed histological and ultrastructural analyses. In the rats that did not undergo tumor transplantation, minimal detectable morphological changes in the microvasculature of the central nervous system were observed after treatment, both in the immediate posttreatment phase and at 10 months. Light microscopy of cerebral cortex and caudate nucleus showed normal cytoarchitecture with no evidence of vessel occlusion, hyalinization, thickening, or reactive gliosis. Electron microscopy demonstrated that the junctional complexes of the endothelial cells, the basal lamina, and the perivascular glia were comparable in both treated and control animals. In those animals examined at 18 months, pathological membrane-bound clusters of electron-dense vesicles were seen in pericytes. In the rats implanted with gliomas, vascular proliferation with evidence of breakdown of the blood-brain barrier and vasogenic edema occurred. In the irradiated animals, we noted increased peritumoral edema 3 days after treatment. At seven days, both increased peritumoral edema and necrosis were noted in the rats treated with BNCT. These observations show that the normal microvasculature of the central nervous system tolerates BNCT at the treatment parameters used in our experimental model; the progressive edema and necrosis found in the peritumoral region after BNCT indicate a pathological endothelial response.

Animals↗
PubMed1988

Potential metabolic mutagens of caffeine and various methylxanthines.

Xanthine N-carbinols, potential metabolites of caffeine and other methylxanthines, have been synthesized, characterized, and derivatized. Such intermediates, the initial metabolites arising from the cytochrome P-450 oxidation of the nitrogen-bound methyl groups, may be viewed as biological N-carbinols capable of alkylating proteins and nucleic acids. Evaluation of these compounds against Salmonella typhimurium, strain TA100, has demonstrated that, in contrast to caffeine, 7-hydroxymethyltheophylline and the 3,7-bis(hydroxymethyl)-1-methylxanthine mixture did exhibit cytotoxicity. There was no evidence of mutagenesis and it is possible that the Ames assay system is not applicable to N-carbinols.

Animals↗
PubMed1987

Boronation of antibodies with mercaptoundecahydro-closo-dodecaborate(2-) anion for potential use in boron neutron capture therapy.

The anionic polyhedral borane derivative, mercaptoundecahydro-closo-dodecaborate(2-), has been evaluated as a boronating agent for antibodies. The objective of these studies was the selective delivery of boron to neoplasms for neutron capture therapy. Incubation of a large excess of this anion with the polyclonal antibody antithymocyte globulin (ATG) resulted in the incorporation of 9-13 mol of the anion per mol of antibody. The extent of boron incorporation into the protein was measured either by tritium-labeled B12H11SH2- or by direct boron determination with neutron activation analysis. The nature of the covalent linkage of the anion to the antibody appeared to involve the formation of a new disulfide bond by a thiol-disulfide exchange. The number of boron atoms incorporated into antibodies by this method appeared to be inadequate for neutron capture therapy. However, such boronated antibodies may have potential for the detection of molecules of biologic interest by means of electron energy loss spectroscopy.

Antibodies, Monoclonal↗
PubMed1986

Adult decisions.

Explore the source record for details and available documents.

Adult↗
PubMed1985

Dicesium N-succinimidyl 3-(undecahydro-closo-dodecaboranyldithio)propionate, a novel heterobifunctional boronating agent.

The synthesis of a novel heterobifunctional agent, dicesium N-succinimidyl 3-(undecahydro-closo-dodecaboranyldithio)propionate, is described. This structure contains an active ester component known to react rapidly under very mild conditions with amino groups of proteins, resulting in covalent linkage. With use of this boronating agent, approximately 480 boron atoms have been incorporated per molecule of a polyclonal antibody directed against human thymocytes and 1300 boron atoms per molecule were incorporated into a monoclonal antibody, 17-1A, directed against human colorectal carcinoma cells. Binding of the boronated antibodies to the corresponding target cells was demonstrated by means of membrane immunofluorescence. There was some loss in reactivity, as determined by fluorescent end point titers, but specificity remained unchanged. The data suggest that boronated antibodies potentially could be used to selectively deliver boron-10 to tumor cells in order to achieve their destruction by neutron capture.

Antibodies↗