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Proton nuclear magnetic resonance measurement of p-boronophenylalanine (BPA): a therapeutic agent for boron neutron capture therapy.

Noninvasive in vivo quantitation of boron is necessary for obtaining pharmacokinetic data on candidate boronated delivery agents developed for boron neutron capture therapy (BNCT). Such data, in turn, would facilitate the optimization of the temporal sequence of boronated drug infusion and neutron irradiation. Current approaches to obtaining such pharmacokinetic data include: positron emission tomography employing F-18 labeled boronated delivery agents (e.g., p-boronophenylalanine), ex vivo neutron activation analysis of blood (and very occasionally tissue) samples, and nuclear magnetic resonance (NMR) techniques. In general, NMR approaches have been hindered by very poor signal to noise achieved due to the large quadrupole moments of B-10 and B-11 and (in the case of B-10) very low gyromagnetic ratio, combined with low physiological concentrations of these isotopes under clinical conditions. This preliminary study examines the feasibility of proton NMR spectroscopy for such applications. We have utilized proton NMR spectroscopy to investigate the detectability of p-boronophenylalanine fructose (BPA-f) at typical physiological concentrations encountered in BNCT. BPA-f is one of the two boron delivery agents currently undergoing clinical phase-I/II trials in the U.S., Japan, and Europe. This study includes high-resolution 1H spectroscopic characterization of BPA-f to identify useful spectral features for purposes of detection and quantification. The study examines potential interferences, demonstrates a linear NMR signal response with concentration, and presents BPA NMR spectra in ex vivo blood samples and in vivo brain tissues.

Boron Compounds↗

Long-term infusions of p-boronophenylalanine for boron neutron capture therapy: evaluation using rat brain tumor and spinal cord models.

Rat 9L gliosarcoma cells infiltrating the normal brain have been shown previously to accumulate only approximately 30% as much boron as the intact tumor after administration of the boronated amino acid p-boronophenylalanine (BPA). Long-term i.v. infusions of BPA were shown previously to increase the boron content of these infiltrating tumor cells significantly. Experiments to determine whether this improved BPA distribution into infiltrating tumor cells after a long-term i.v. infusion improves tumor control after BNCT in this brain tumor model and whether it has any deleterious effects in the response of the rat spinal cord to BNCT are the subjects of the present report. BPA was administered in a fructose solution at a dose of 650 mg BPA/kg by single i.p. injection or by i.v. infusion for 2 h or 6 h, at 330 mg BPA/kg h(-1). At 1 h after the end of either the 2-h or the 6-h infusion, the CNS:blood (10)B partition ratio was 0.9:1. At 3 h after the single i.p. injection, the ratio was 0.6:1. After spinal cord irradiations, the ED(50) for myeloparesis was 14.7 +/- 0.4 Gy after i.p. administration of BPA and 12.9 +/- 0.3 Gy in rats irradiated after a 6-h i.v. infusion of BPA; these values were significantly different (P < 0.001). After irradiation with 100 kVp X rays, the ED(50) was 18.6 +/- 0.1 Gy. The boron compound biological effectiveness (CBE) factors calculated for the boron neutron capture dose component were 1.2 +/- 0.1 for the i.p. BPA administration protocol and 1.5 +/- 0.1 after irradiation using the 6-h i.v. BPA infusion protocol (P < 0.05). In the rat 9L gliosarcoma brain tumor model, the blood boron concentrations at 1 h after the end of the 2-h infusion (330 mg BPA/kg h(-1); n = 15) or after the 6-h infusion (190 mg BPA/kg h(-1); n = 13) were 18.9 +/- 2.2 microg 10B/g and 20.7 +/- 1.8 microg 10B/g, respectively. The irradiation times were adjusted individually, based on the preirradiation blood sample, to deliver a predicted 50% tumor control dose of 8.2 Gy ( approximately 30 photon-equivalent Gy) to all tumors. In the present study, the long-term survival was approximately 50% and was not significantly different between the 2-h and the 6-h infusion groups. The mode of BPA administration and the time between administration and irradiation influence the 10B partition ratio between the CNS and the blood, which in turn influences the measured CBE factor. These findings underline the need for clinical biodistribution studies to be carried out to establish 10B partition ratios as a key component in the evaluation of modified administration protocols involving BPA.

Animals↗

Sensitizing effect of the phosphatidylinositol 3-kinase inhibitor wortmannin on thermal neutron irradiation with or without boron compound.

Wortmannin, a phosphatidylinositol 3-kinase inhibitor, has been found to be an efficient radiosensitizer. We have investigated the radiosensitizing effect of wortmannin on cell killing against thermal neutrons produced by the Kyoto University Research (KUR) reactor. Wortmannin was added to cells 2 hours before irradiation and removed 16 hours after irradiation. Cells were irradiated by thermal neutrons with or without boron at 0, 10, and 20 ppm. The biological end point of cell survival was measured by colony formation assay. The D0 values of thermal neutrons in different boron concentrations, 0, 10, and 20 ppm were 1.2, 1.1, and 1.0 Gy, respectively. When cells were treated with wortmannin, the D0 values decreased to 0.5, 0.6, and 0.8 Gy at boron concentrations of 0, 10, and 20 ppm, respectively. Wortmannin enhanced cell death against thermal neutron irradiation especially in the absence of boron. Thus, our results suggest that wortmannin may be useful to combine with boron neutron capture therapy (BNCT) treatment when boron uptake by cells is limited.

Androstadienes↗

Folate receptor-targeted liposomes as possible delivery vehicles for boron neutron capture therapy.

BACKGROUND: The folate receptor is amplified in a variety of human tumors including over 90% of ovarian carcinoma. FR-targeted liposomes have previously been used by us to selectively deliver entrapped boron-containing compounds to tumor cells for neutron capture therapy (NCT). In the present study we have evaluated the delivery of Na3(B20H17NH3), which has been loaded into FR-targeted liposomes, in mice bearing xenograft implants of FR (+) KB subcutaneous tumor. MATERIALS AND METHODS: Na3(B20H17NH3) was passively entrapped into FR-targeted liposomes, which were administered intravenously into nude mice bearing s.c. implants of the FR(+) human oral carcinoma KB cell line. Normal and tumor boron content was measured by direct current plasma-atomic emission spectroscopy. RESULTS: Mice that received FR-targeted liposomes containing boron showed the highest tumor boron levels at 24 hours (6.1 micrograms/g) and tumor/blood boron ratios continued to rise for up to 120 hours. CONCLUSION: Boron delivery via FR-targeted liposomes is feasible and potentially can improve tumor uptake compared to non-targeted liposomes, and may improve cellular and subcellular localization.

Animals↗

New carborane-based compounds for boron neutron capture therapy: binding and toxicity of ANC-1, DAC-1 and B-Et-11-OMe in cultured human glioma and mouse melanoma cells.

The toxicity and binding of the three new carborane based compounds: 2 (1,2-dicarba-closo-dodecaborane (12)-1(-yl-methoxy)-2-(3-amino-propyl))-1,3-propanediol, called DAC-1; 7-(3-amino-propyl)-7,8-dicarba-nido-undecarborate (-1) called ANC-1; and rac-1-(9-o-carboranyl)-nonyl-2-methyl-glycero-3- phosphocholine, called B-Et-11-OMe, were analyzed with cultured human glioma cells, U-343MGa, and mouse melanoma cells, B16, as biological models. The previously developed compound di-sodium undecahydro-mercapto-closo-dodecarborate (BSH), which is tested for therapy of malignant gliomas, was analyzed for comparison. In the toxicity tests the cells were exposed to the substances at cell culture medium concentrations in the range 0-50 ppm boron for 1 or 20 h and thereafter analyzed regarding growth. Growth-disturbing effects were seen for the two compounds DAC-1 and B-Et-11-OMe at the concentrations corresponding to 15 and 50 ppm boron, respectively. The compounds ANC-1 and BSH showed no growth-disturbing effects at the tested concentrations. In the binding tests, the cells were incubated for 20 h at about the highest compound concentrations that did not cause growth disturbances. The boron content in the cells was then determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES) and in some cases ICP-mass spectrometry (ICP-MS). The most extensive binding was seen for DAC-1 and B-Et-11-OMe, which accumulated boron to about 100 and 60 times, respectively, compared with the concentration in the culture medium. The compound ANC-1 also accumulated boron in the cells but the boron could be easily washed out indicating no or only a weak binding. BSH did not accumulate. Further analysis should be made regarding biological properties such as intracellular compartmentalization, metabolic interference and tumor specificity of the compounds DAC-1 and B-Et-11-OMe.

Animals↗

New sensitive and selective fluorescent probes for fluoride using boronic acids.

We report the spectroscopic characterization of six fluorescent probes for fluoride sensing and/or monitoring. All probes are based on the ability of the boronic acid group to interact with fluoride. The probes combine electron donor and withdrawing groups and involve the excited charge transfer mechanism. The change between the neutral form of the boronic acid group [R-B(OH)2], which is an electron withdrawing group, and the anionic trifluoro form [R-BF3-], which is an electron donating group, is at the origin of the different spectral changes observed for the investigated probes. Two probes are based on the stilbene structure where the boronic group in the 4 position is coupled with a cyano group, in one case, and the dimethylamino group in the other case, both at the 4' position. Another probe is based on the diphenyl-1,4-butadiene possessing the boronic acid group in the 4' position and a dimethylamino group in the 4" position. One probe is based on the diphenyloxazole structure having both the boronic acid and the dimethylamino groups in para positions. The two last probes reported are based on the benzalacetophenone (chalcone) structure, again coupling the boronic acid and dimethylamino groups. All probes show spectral shifts and/or intensity changes in the presence of fluoride resulting in most of the cases to a wavelength-ratiometric way for the detection and/or analysis of fluoride. Selectivity and stability constants are also presented and discussed.

Boronic Acids↗

The development of photometric sensors for boronic acids.

Boronic acids bind certain 1,2- and 1,3-diols with high affinity through reversible formation of boronate esters. They have been utilized as the recognition moiety for artificial receptors, particularly receptors for carbohydrates that have cis-diol moieties. Therefore, sensors for boronic acids could serve as universal reporters for monitoring boronate formation. This paper reports the design and synthesis of a series of photometric chemosensors for phenylboronic acid using diethanolamine as the recognition moiety. Diethanolamine, which binds strongly to boronic acids, has been linked to three different types of optical reporters. A photoinduced electron transfer system based on the anthracene fluorophore has been used to create sensors that show up to a fivefold increase in fluorescent intensity in the presence of millimolar concentrations of phenylboronic acid. Sensor designs based on the restriction of free rotation of extended pi systems and on the perturbed electronic properties of azo dyes are also included. This work demonstrates that sensors based on several different designs can be used for the detection of boronic acids.

Azo Compounds↗

Tourmaline mineralization in the Barberton greenstone belt, South Africa: early Archean metasomatism by evaporite-derived boron.

Tourmaline-rich rocks are common in the low-grade, interior portions of the Barberton greenstone belt of South Africa, where shallow-marine sediments and underlying altered basaltic and komatiitic lavas contain up to 50% tourmaline. The presence of tourmaline-bearing rip-up clasts, intraformational tourmaline pebbles and tourmaline-coated grains indicate that boron mineralization was a low-temperature, surficial process. The association of these lithologies with stromatolites, evaporites, and shallow-water sedimentary structures and the virtual absence of tourmaline in correlative deep-water facies rocks in the greenstone belt strengthens this model. Five tourmaline-bearing lithologic groups (basalts, komatiites, evaporite-bearing sediments, stromatolitic sediments, and quartz veins) are distinguished based on field, petrographic, and geochemical criteria. Individual tourmaline crystals within these lithologies show internal chemical and textural variations that reflect continued growth through intervals of change in bulk-rock and fluid composition accompanying one or more metasomatic events. Large single-crystal variations exist in Fe/Mg, Al/Fe, and alkali-site vacancies. A wide range in tourmaline composition exists in rocks altered from similar protoliths, but tourmalines in sediments and lavas have similar compositional variations. Boron-isotope analyses of the tourmalines suggest that the boron enrichment in these rocks has a major marine evaporitic component. Sediments with gypsum pseudomorphs and lavas altered at low temperatures by shallow-level brines have the highest delta 11B values (+2.2 to -1.9%); lower delta 11B values of late quartz veins (-3.7 to -5.7%) reflect intermediate temperature, hydrothermal remobilization of evaporitic boron. The delta 11B values of tourmaline-rich stromatolitic sediments (-9.8 and -10.5%) are consistent with two-stage boron enrichment, in which earlier marine evaporitic boron was hydrothermally remobilized and vented in shallow-marine or subaerial sites, mineralizing algal stromatolites. The stromatolite-forming algae preferentially may have lived near the sites of hydrothermal discharge in Archean times.

Boron↗

Effects of boron on growing pullets.

The effect of dietary boron on bone ash content and on the ultimate shear force, stress, and fracture energy of the tibia, femur, humerus, and radius from white Leghorn pullets were investigated. There was a significant increase in the shear force of the tibia and femur for pullets supplemented with 50 and 100 mg/kg of dietary boron. There was a significant increase in the shear stress of the tibia at 50 and 100 mg/kg of boron, and also an increase in shear fracture energy at 50 and 100 mg/kg boron for the femur. Tibia bone ash content increased significantly at 50, 100, and 200 mg/kg boron with the highest value at 50 mg/kg. Even though there was not a significant increase in body wt at 50 and 100 mg/kg boron, the pullets fed these supplements were consistently heavier than the control group.

Animals↗

Binding of lithium and boron to human plasma proteins.

The binding of lithium and boron, at normal physiological levels, to plasma proteins has been investigated by the techniques of precipitation with ethyl alcohol and gel chromatography. Assays of lithium and boron were made by thermal neutron activation and mass spectrometric assay of 3He and 4He. Results of alcohol precipitation experiments for plasma from two apparently healthy donors showed that 13+/-4% and 16+/-3% of the lithium in plasma is protein bound, but essentially no boron is bound under the conditions used. We believe that because of denaturation of proteins which occurs during alcohol precipitation, these percentages represent lithium and boron tightly bound to protein molecules. The results of the gel-chromatography experiment, on the other hand, showed that lithium and boron are bound to a wide range of plasma proteins, from low (approximately 60,000 amu) to high (approximately 1,000,000 amu) molecular weights, and to very low- (approximately 6000 amu) molecular-weight ligands. Although a clear identification of the specific proteins which bind lithium and boron cannot be made at present, some possibilities can be suggested.

Blood Proteins↗

Dosimetry of the boron neutron capture reaction for BNCT and BNCEFNT.

The use of paired proportional counters, constructed from A-150 tissue equivalent plastic (TEP) and A-150 TEP loaded with an appropriate amount of 10B (50 to 200 ppm), for the dosimetry of the boron neutron capture reaction has been investigated for several years at the Gershenson Radiation Oncology Center. This method has been used for determining the dose components (fast neutron, gamma ray and boron capture product dose) in both Boron Neutron Capture Therapy (BNCT) beams and in beams proposed for boron neutron capture enhancement of fast neutron therapy (BNCEFNT). A disadvantage of this method, when standard 1/2" diameter Rossi type proportional counters are used, is that the beam intensity must be relatively low in order to avoid saturation effects (pulse pile-up) in the counter. This is a major problem if measurements are to be made in a reactor beam, since reducing the beam intensity generally results in a change in the neutron spectrum. In order to overcome this problem, miniature cylindrical proportional counters have been developed which may be used in high intensity beams. The operational characteristics of these counters are compared with the standard 1/2" spherical counters. A further disadvantage of proportional counters is the relatively long time it takes to collect data, particularly if detailed information (depth-dose curves and beam profiles) is required. This problem could be overcome by using a set of ionization chambers (an A-150 TEP chamber, a Mg chamber and a Mg chamber with a 25 microns boron loaded inner wall) which can be scanned in a water phantom. After calibration against the paired proportional counters it should be possible to extract the fast neutron, gamma ray and boron neutron capture product doses from measurements made with these three ionization chambers. A set of such chambers has been used to make preliminary measurements in a fast neutron beam and the results of these measurements are presented.

Boron Neutron Capture Therapy↗

Characterization of the distribution of the sintering activator boron in powder metallurgical steels with SIMS.

Powder metallurgy is a well-established method for manufacturing ferrous precision parts. A very important step is sintering, which can be strongly enhanced by the formation of a liquid phase during the sintering process. Boron activates this process by forming such a liquid phase at about 1200 degrees C. In this work, the sintering of Fe-B was performed under the protective atmospheres of hydrogen, argon or nitrogen. Using different grain sizes of the added ferroboron leads to different formations of pores and to the formation of secondary pores. The effect of boron was investigated by means of Secondary Ion Mass Spectrometry (SIMS) supported by Scanning Electron Microscopy (SEM) and Light Microscopy (LM). To verify the influence of the process parameters on the mechanical properties, the microstructure (pore shape) was examined and impact energy measurements were performed. The concentrations of B in different samples were varied from 0.03-0.6 weight percent (wt%). Higher boron concentrations are detectable by EPMA, whereas the distributions of boron in the samples with interesting overall concentration in the low wt% range are only detectable by means of SIMS. This work shows that the distribution of boron strongly depends on its concentration and the sintering atmosphere used. At low concentration (up to 0.1 wt%) there are boride precipitations; at higher concentration there is a eutectic iron-boron grain boundary network. There is a decrease of the impact energy observed that correlates with the amount of eutectic phase.

Argon↗

Effects of boron deficiency in cell suspension cultures of Populus alba L.

Cell suspension cultures of Populus alba L. (original cells) require at least 10 microM boron for appropriate growth. Using original cells we established a cell line, T-5B, which can grow in a medium containing low levels of boron (5 microM). The level of boron localized in the cell walls of T-5B cells was one-half that found in the cell walls of original cells maintained in medium containing 100 microM boron, and the level of the rhamnogalacturonan II dimer, cross-linked by a borate ester, also decreased in the former. The sugar composition of whole cell walls of the T-5B cell line was similar that of the original cells, however pectic polysaccharides composed of arabinose or galacturonic acid were easily extracted from T-5B cell walls with 50 mM trans-1,2-cyclohexanediamine-N,N,N',N'-tetraacetic acid. Our results suggest that boron deficiency causes a weakening of the interaction among pectic polysaccharides due to a decrease in boron-rhamnogalacturonanII cross-linkage.

Boron↗

Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States).

OBJECTIVE: To determine: (1) the correlation of prostate cancer incidence and mortality with groundwater boron and selenium concentrations; and (2) the impact of boron on prostate cancer cell proliferation during co-treatment with alternative chemo-preventative agents, along with boron pre-treatment effects on cell sensitivity to ionizing radiation. METHODS: For regression analysis, data on prostate cancer incidence and mortality were obtained from the Texas Cancer Registry, while groundwater boron and selenium concentrations were derived from the Texas Water Development Board. Cultured DU-145 prostate cancer cells were used to assess the impact of boric acid on cell proliferation when applied in combination with selenomethionine and genistein, or preceding radiation exposure. RESULTS: Groundwater boron levels correlated with a decrease in prostate cancer incidence (R = 0.6) and mortality (R = 0.6) in state planning regions, whereas selenium did not (R = 0.1; R = 0.2). Growth inhibition was greater during combined treatments of boric acid and selenomethionine, or boric acid and genistein, versus singular treatments. 8-day boric acid pre-exposure enhanced the toxicity of ionizing radiation treatment, while dose-dependently decreasing the expression of anti-apoptotic protein Bcl-2. CONCLUSIONS: Increased groundwater boron concentrations, across the state of Texas, correlate with reduced risk of prostate cancer incidence and mortality. Also, boric acid improves the anti-proliferative effectiveness of chemo-preventative agents, selenomethionine and genistein, while enhancing ionizing radiation cell kill.

Anticarcinogenic Agents↗

Current status of 10B-neutron capture therapy: enhancement of tumor dose via beam filtration and dose rate, and the effects of these parameters on minimum boron content: a theoretical evaluation.

At least 8 classes of compounds are being evaluated in various laboratories around the world as possible vehicles for the transport of boron to tumor for neutron capture therapy (NCT). A parameter of major importance is the minimum concentration of boron needed in tumor in order to produce improved results in cancer therapy. Calculations are made here of the minimum boron content in tumor necessary for NCT. These estimations are obtained for various neutron beams, on the basis of therapeutic gain produced by the effective dose (absorbed dose X relative biological effect). The effects of repair are considered, in anticipation of having boronated bio-molecules with selective and long-term binding to tumor cells, thus allowing protracted irradiations. Pure epithermal neutron beams (free of significant fast neutron and gamma contamination) are found to offer major advantages, particularly when the effects of repair are included. The various boron compounds being investigated for NCT are evaluated on the basis of necessary minimum boron content in tumor.

Boron↗

Derivations of relative biological effectiveness for the high-let radiations produced during boron neutron capture irradiations of the 9L rat gliosarcoma in vitro and in vivo.

PURPOSE: Relative biological effectiveness (RBE) values for the high linear-energy-transfer particles produced during boron neutron capture therapy have generally been based on theoretical considerations or in vitro experiments. The purpose of this study was to independently determine RBE values for all of the boron neutron capture therapy dose components. METHODS AND MATERIALS: Clonogenic cell survival data were obtained for 9L rat gliosarcoma cells irradiated in the Brookhaven Medical Research Reactor thermal neutron beam both in vitro and as an intracerebral tumor. These data were analyzed using the linear quadratic model for cell survival to derive measured RBE values for all beam components and for a number of different boron compounds. RESULTS: In the absence of boron, the combined effects of the protons from the nitrogen capture, 14N(n,p)14C, and the fast neutron scatter, 1H(n,n')p, reactions generated RBEs of 3.7 in vitro and 3.2 in an in vivo/in vitro excision assay, compared to 250 kVp X rays using an end point of 1% cell survival. Apparent RBEs for the 10B(n,alpha)7Li reaction products were calculated from cell survival data following reactor irradiations in the presence of the amino acid p-boronophenylalanine, the sulfhydryl dodecaborate monomer or dimer, or boric acid. Apparent RBEs for the 10B(n,alpha)7Li reaction ranged from 1.2 to 9.8 depending on which boron compound was used. RBEs from the in vitro studies were consistently higher than from the in vivo/in vitro studies. Under any conditions, the apparent RBE for the 10B(n,alpha)7Li reaction with p-boronophenylalanine was higher than that with any other boron compound tested. CONCLUSIONS: Generally accepted RBE values for the fast neutron and 14N(n,p)14C reaction components of the total dose are too low. The apparent RBEs calculated for the 10B(n,alpha)7Li reaction were compound-dependent and consistent with differences in the distribution of 10B relative to glioma cell nuclei.

Animals↗

A study of boron adsorption onto activated sludge.

Boron adsorption onto activated sludge was investigated using bench-scale reactors under simulated wastewater treatment conditions. Two experiments, continuous flow and batch, were performed. Boron concentrations were determined by means of inductively coupled plasma mass spectrometry. The results of the continuous-flow experiment indicated that a small amount of boron accumulated on the activated sludge and its concentration in the sludge depended on the nature of the biota in the sludge. Freundlich and Langmuir isotherm plots generated using the data from the batch experiment indicated that boron was adsorbed onto rather than absorbed into the sludge. The Freundlich constants, k and 1/n, were determined to be 26 mg/kg and 0.87. These values indicate that activated sludge has a limited capacity for boron adsorption and thus utilization of the excess sludge for farmland may not be toxic to plant at least boron concern.

Adsorption↗

Intra-arterial administration of sodium borocaptate (BSH)/lipiodol emulsion delivers B-10 to liver tumors highly selectively for boron neutron capture therapy: experimental studies in the rat liver model.

PURPOSE: Boron neutron capture therapy (BNCT) is particle radiotherapy with alpha ((4)He) particle and recoiled lithium nucleus ((7)Li) derived from a reaction of boron ((10)B) and thermal neutron. We investigated applying BNCT to malignant liver tumors. The purpose of the present study was to reveal the efficacy for administration of emulsion of a boron compound (sodium borocaptate; BSH) and lipiodol via a hepatic artery using a rat liver tumor model. METHODS AND MATERIALS: Rat liver tumors were developed by direct injection of Walker 256 cells into the liver parenchyma. BSH (75 mg/kg)/lipiodol (0.3 mL/kg) emulsion was administered via the hepatic artery. Boron concentrations in the tumors, liver, and blood were measured at 1, 6, and 12 h after administration. Neutron capture radiography (NCR) was taken to confirm the selective accumulation of (10)B in the liver tumors. RESULTS: Boron concentrations in the liver tumors and the tumor/liver (T/L) boron concentration ratio at 1, 6, and 12 h after administration of BSH/lipiodol emulsion (concentration: T/L ratio) were 479.2 ppm: 4.0, 197.3 ppm: 14.9, and 96.5 ppm: 6.6, respectively. Highly selective irradiation was clearly demonstrated by the NCR images. CONCLUSIONS: Intra-arterial administration of BSH/lipiodol emulsion is effective method for delivering high concentration of (10)B selectively to the liver tumors.

Animals↗