Uptake of [¹8F]tetrafluoroborate in MCF-7 Breast Cancer Cells is Induced after Stimulation of the Sodium Iodide Symporter.

BACKGROUND: The human sodium iodide symporter (hNIS) has been the most important target in nuclear medicine regarding thyroid-related diseases. Although hNIS-expression can also be determined in extra-thyroidal tumors, imaging hNIS with positron emission tomography has not been exploited clinically. OBJECTIVE: Here, we evaluated the accumulation of the novel hNIS-substrate [18F]tetrafluoroborate ([18F]TFB) in the endogenously hNIS-expressing breast cancer cell line MCF-7 after an improved radiosynthesis and pharmacological stimulation. METHODS: [18F]TFB was prepared under mild reaction conditions (40°C, 25 min) and its uptake properties were investigated in MCF-7 cells pretreated with a combination of all-trans retinoic acid plus methasone-derivatives and compared to the clinically established tracers [131I]iodide and [99mTc]pertechnetate. Specificity of the tracer accumulation was assessed by inhibition experiments using NaBF4, KSO3F, KI and KIO3. RESULTS: [18F]TFB was obtained with a radiochemical yield of 24.0 ± 6.6 % (n = 17) within 40 min after high pressure liquid chromatography-separation and with 26.8 ± 6.2 % (n = 13) within 45 min after adapting the procedure on a synthesis module using higher starting activities (> 10 GBq). After pharmacological treatment, a 4-fold increase in hNIS-expression on the MCF-7 cell surface was achieved, resulting in a significantly higher [18F]TFB uptake into the cells (up to 58-fold) as compared to control experiments. Inhibition studies using various NIS-substrates confirmed the specificity of [18F]TFB for hNIS. CONCLUSION: [18F]TFB was shown to be a promising hNIS-substrate in our model using the human MCF-7 breast cancer cell line mandating in vivo evaluations in xenografted studies and in patients.

Angiogenesis and Full-Thickness Wound Healing Efficiency of a Copper-Doped Borate Bioactive Glass/Poly(lactic- co-glycolic acid) Dressing Loaded with Vitamin E in Vivo and in Vitro.

There is an urgent demand for wound healing biomaterials because of the increasing frequency of traffic accidents, industrial contingencies, and natural disasters. Borate bioactive glass has potential applications in bone tissue engineering and wound healing; however, its uncontrolled release runs a high risk of rapid degradation and transient biotoxicity. In this study, a novel organic-inorganic dressing of copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) loaded with vitamin E (0-3.0 wt % vitamin E) was fabricated to evaluate its efficiency for angiogenesis in cells and full-thickness skin wounds healing in rodents. In vitro results showed the dressing was an ideal interface for the organic-inorganic mixture and a controlled release system for Cu2+ and vitamin E. Cell culture suggested the ionic dissolution product of the copper-doped and vitamin E-loaded dressing showed the best migration, tubule formation, and vascular endothelial growth factor (VEGF) secretion in human umbilical vein endothelial cells (HUVECs) and higher expression levels of angiogenesis-related genes in fibroblasts in vitro. Furthermore, this dressing also suggested a significant improvement in the epithelialization of wound closure and an obvious enhancement in vessel sprouting and collagen remodeling in vivo. These results indicate that the copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) dressing loaded with vitamin E is effective in stimulating angiogenesis and healing full-thickness skin defects and is a promising wound dressing in the reconstruction of full-thickness skin injury.

18F-Tetrafluoroborate, a PET Probe for Imaging Sodium/Iodide Symporter Expression: Whole-Body Biodistribution, Safety, and Radiation Dosimetry in Thyroid Cancer Patients.

We report the safety, biodistribution, and internal radiation dosimetry, in humans with thyroid cancer, of 18F-tetrafluoroborate (18F-TFB), a novel PET radioligand for imaging the human sodium/iodide symporter (hNIS). Methods: Serial whole-body PET scans of 5 subjects with recently diagnosed thyroid cancer were acquired before surgery for up to 4 h after injection of 184 ± 15 MBq of 18F-TFB. Activity was determined in whole blood, plasma, and urine. Mean organ-absorbed doses and effective doses were calculated via quantitative image analysis and using OLINDA/EXM software. Results: Images showed a high uptake of 18F-TFB in known areas of high hNIS expression (thyroid, salivary glands, and stomach). Excretion was predominantly renal. No adverse effects in relation to safety of the radiopharmaceutical were observed. The effective dose was 0.0326 ± 0.0018 mSv/MBq. The critical tissues/organs receiving the highest mean sex-averaged absorbed doses were the thyroid (0.135 ± 0.079 mSv/MBq), stomach (0.069 ± 0.022 mSv/MBq), and salivary glands (parotids, 0.031 ± 0.011 mSv/MBq; submandibular, 0.061 ± 0.031 mSv/MBq). Other organs of interest were the bladder (0.102 ± 0.046 mSv/MBq) and kidneys (0.029 ± 0.009 mSv/MBq). Conclusion: Imaging using 18F-TFB imparts a radiation exposure similar in magnitude to many other 18F-labeled radiotracers. 18F-TFB shows a biodistribution similar to 99mTc-pertechnetate, a known nonorganified hNIS tracer, and is pharmacologically and radiobiologically safe in humans. Phase 2 trials for 18F-TFB as an hNIS imaging agent are warranted.

[18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model.

Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [18F]tetrafluoroborate ([18F]BF4-) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Radionuclide imaging with [18F]BF4- (PET/CT) was compared to the conventional tracer [123I]iodide (sequential SPECT/CT). We found that [18F]BF4- was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster and more complete clearance from circulation. [18F]BF4--PET was also highly specific as in all detected tissues cancer cell presence was confirmed microscopically. Undetected comparable tissues were similarly found to be free of metastasis. Metastasis detection by routine metabolic imaging with [18F]FDG-PET failed due to low standard uptake values and low contrast caused by adjacent metabolically active organs in this model. [18F]BF4--PET combined with NIS expressing disease models is particularly useful whenever preclinical in vivo cell tracking is of interest.

Synthesis and evaluation of (18)F-trifluoroborate derivatives of triphenylphosphonium for myocardial perfusion imaging.

Four trifluoroborate derivatives of phosphonium cations 2a-d were radiolabeled with fluorine-18 ((18)F) and evaluated for imaging myocardial perfusion with positron emission tomography (PET). Tracers were radiolabeled simply via (18)F-(19)F isotope exchange reaction in acidic (pH 2) aqueous solution. On average, [(18)F]2a-d were obtained in 10-17% non-decay-corrected radiochemical yield with 25.9-48.1GBq/µmol specific activity, and >96% radiochemical purity. In vitro stability study showed no decomposition of [(18)F]2a-d after being incubated in mouse plasma for up to 2h. Myocardial uptake in mice was visualized in PET images by using [(18)F]2b-d but not [(18)F]2a. [(18)F]2a-d were stable against in vivo defluorination as no significant bone uptake was observed. Despite sub-optimal heart uptake of [(18)F]2b-d, we successfully demonstrated that (18)F-(19)F isotope exchange reaction on trifluoroborates could be a promising strategy for the design of potential (18)F-labeled tracers even for intracellular targets.

Dual mode fluorescent (18)F-PET tracers: efficient modular synthesis of rhodamine-[cRGD]2-[(18)F]-organotrifluoroborate, rapid, and high yielding one-step (18)F-labeling at high specific activity, and correlated in vivo PET imaging and ex vivo fluorescence.

The design of dual mode fluorescent-PET peptidic tracers that can be labeled with [(18)F]fluoride at high specific activity and high yield has been challenged by the short half-life of (18)F and its aqueous indolence toward nucleophilic displacement, that often necessitates multistep reactions that start with punctiliously dry conditions. Here we present a modular approach to constructing a fluorescent dimeric peptide with a pendant radioprosthesis that is labeled in water with [(18)F]fluoride ion in a single, user-friendly step. The modular approach starts with grafting a new zwitterionic organotrifluoroborate radioprosthesis onto a pentaerythritol core with three pendent alkynes that enable successive grafting of a bright fluorophore (rhodamine) followed by two peptides (cylcoRGD). The construct is labeled with [(18)F]fluoride via isotope exchange within 20 min in a single step at high specific activity (>3 Ci/µmol) and in good yield to provide 275 mCi and high radiochemical purity. Neither drying of the [(18)F]fluoride ion solution nor HPLC purification of the labeled tracer is required. Facile chemical synthesis of this dual mode tracer along with a user-friendly one-step radiolabeling method affords very high specific activity. In vivo PET images of the dual mode tracer are acquired at both high and low specific activities. At very high specific activity, i.e., 3.5 Ci/µmol, tumor uptake is relatively high (5.5%ID/g), yet the associated mass is below the limits of fluorescent detection. At low specific activity, i.e., 0.01 Ci/µmol, tumor uptake in the PET image is reduced by approximately 50% (2.9%ID/g), but the greater associated mass enables fluorescence detection in the tumor. These data highlight a facile production of a dual mode fluorescent-PET tracer which is validated with in vivo and ex vivo images. These data also define critical limitations for the use of dual mode tracers in small animals.

Diffusion of peroxides through dentine in vitro with and without prior use of a desensitizing varnish.

Different bleaching regimens are used in dentistry possibly penetrating the dentine and affecting the pulp. The aim of the present study was to investigate peroxide diffusion through dentine pre-treated with a desensitizing varnish (Vivasens®) in a standardized in vitro setup during application of different bleaching materials. The penetration was tested using 1.3-mm-thick bovine dentine slabs. The following bleaching materials were tested with and without prior application of the desensitizing varnish on the external side of the dentine slabs: Vivastyle, Whitestrips, Simply White, Opalescence (external bleaching), and sodium perborate (internal bleaching, only tested without varnish; n = 8 samples per subgroup). The penetration of peroxides was measured photometrically using 4-aminoantipyrin as a substrate, the penetration of peroxides was monitored over 240 min. All bleaching agents yielded a diffusion of peroxides through the dentine, the kinetics of penetration were approximately linear for all materials tested. The significantly highest diffusion of peroxides was observed with Opalescence, the lowest with sodium perborate. The adoption of the desensitizing varnish reduced the diffusion of peroxides significantly for all external bleaching materials. Peroxides penetrated the dentine during application of bleaching materials; the penetration of peroxides can be reduced by application of a desensitizing agent.

Peroxide penetration from the pulp chamber to the external root surface after internal bleaching.

PURPOSE: To quantify the amount of peroxide penetration from the pulp chamber to the external surface of teeth during the walking bleaching technique. METHODS: Seventy-two bovine lateral incisors were randomly divided over five experimental groups and one control (n = 12 per group): (1) 35% hydrogen peroxide (HP); (2) 35% carbamide peroxide (CP); (3) sodium perborate (SP); (4) (HP+SP); (5) (CP+SP) and (6) Control (CG), deionized water. All groups were treated according to the walking bleach technique. After 7 days at 37 degrees C in an acetate buffer solution, 100 microl violet leukocrystal coloring and 50 microl peroxidase was added, producing a blue stain that could be measured in a spectrophotometer and then converted into peroxide microg/ml. RESULTS: G5 exhibited the greatest penetration, while G2 and G3 produced the lowest values. All bleaching agents penetrated from the pulp chamber to the external root surface. There was a direct correlation between the presence of oxidative agents and penetration potential. Sodium perborate in distilled water was less oxidative and appeared to be the least aggressive bleaching agent.

Preparation and in vivo evaluation of radioiodinated closo-decaborate(2-) derivatives to identify structural components that provide low retention in tissues.

INTRODUCTION: In vivo deastatination of (211)At-labeled biomolecules can severely limit their use in endoradiotherapy. Our studies have shown that the use of closo-decaborate(2-) moiety for (211)At-labeling of biomolecules provides high in vivo stability towards deastatination. However, data from those studies have also been suggestive that some astatinated closo-decaborate(2-) catabolites may be retained in tissues. In this study, we investigated the in vivo distributions of several structurally simple closo-decaborate(2-) derivatives to gain information on the effects of functional groups if catabolites are released into the blood system from the carrier biomolecule. METHODS: Thirteen closo-decaborate(2-) derivatives were synthesized and radioiodinated for evaluation. Tissue concentrations of the radioiodinated compounds were obtained in groups of five mice at 1 and 4 h postinjection (pi). Dual-label ((125)I and (131)I) experiments permitted evaluation of two compounds in each set of mice. RESULTS: All of the target compounds were readily synthesized. Radioiodination reactions were conducted with chloramine-T and Na[(125/131)I]I in water to give high yields (75-96%) of the desired compounds. Biodistribution data at 1 and 4 h pi (representing catabolites released into the blood system) showed small differences in tissue concentrations for some compounds, but large differences for others. The results indicate that formal (overall) charge on the compounds could not be used as a predictor of tissue localization or retention. However, derivatives containing carboxylate groups generally had lower tissue concentrations. Acid cleavable hydrazone functionalities appeared to be the best candidates for further study. CONCLUSIONS: Further studies incorporating hydrazone functionalities into pendant groups for biomolecule radiohalogenation are warranted.

Toward [18F]-labeled aryltrifluoroborate radiotracers: in vivo positron emission tomography imaging of stable aryltrifluoroborate clearance in mice.

The use of a boronic ester as a captor of aqueous [(18)F]-fluoride has been previously suggested as a means of labeling biomolecules in one step for positron emission tomography (PET) imaging. For this approach to be seriously considered, the [(18)F]-labeled trifluoroborate should be humorally stable such that it neither leaches free [(18)F]-fluoride to the bone nor accumulates therein. Herein, we have synthesized a biotinylated boronic ester that is converted to the corresponding trifluoroborate salt in the presence of aqueous [(18)F]-fluoride. In keeping with its in vitro aqueous kinetic stability at pH 7.5, the trifluoroborate appears to clear in vivo quite rapidly to the bladder as the stable trifluoroborate salt with no detectable leaching of free [(18)F]-fluoride to the bone. When this labeled biotin is preincubated with avidin, the pharmacokinetic clearance of the resulting complex is visibly altered. This work validates initial claims that boronic esters are potentially useful as readily labeled precursors to [(18)F]-PET reagents.

A new scleroglucan/borax hydrogel: swelling and drug release studies.

The aim of the work was the characterization of a new polysaccharidic physical hydrogel, obtained from Scleroglucan (Sclg) and borax, following water uptake and dimension variations during the swelling process. Furthermore, the release of molecules of different size (Theophylline (TPH), Vitamin B12 (Vit. B12) and Myoglobin (MGB)) from the gel and from the dried system used as a matrix for tablets was studied. The increase of weight of the tablets with and without the loaded drugs was followed together with the relative variation of the dimensions. The dry matrix, in the form of tablets was capable, during the swelling process, to incorporate a relevant amount of solvent (ca. 20 g water/g dried matrix), without dissolving in the medium, leading to a surprisingly noticeable anisotropic swelling that can be correlated with a peculiar supramolecular structure of the system induced by compression. Obtained results indicate that the new hydrogel can be suitable for sustained drug release formulations. The delivery from the matrix is deeply dependent on the size of the tested model drugs. The experimental release data obtained from the gel were satisfactorily fitted by an appropriate theoretical approach and the relative drug diffusion coefficients in the hydrogel were estimated. The release profiles of TPH, Vit. B12 and MGB from the tablets have been analyzed in terms of a new mathematical approach that allows calculating of permeability values of the loaded drugs.

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.

Serum and urinary boron levels in rats after single administration of sodium tetraborate.

The pharmacokinetics of boron was studied in rats by administering a 1 ml oral dose of sodium tetraborate solution to several groups of rats (n=20) at eleven different dose levels ranging from 0 to 0.4 mg/100 g body weight as boron. Twenty-four-hour urine samples were collected after boron administration. After 24 h the average urinary recovery rate for this element was 99.6+/-7.9. The relationship between boron dose and excretion was linear (r=0.999) with a regression coefficient of 0.954. This result suggests that the oral bioavailability (F) of boron was complete. Another group of rats (n=10) was given a single oral injection of 2 ml of sodium tetraborate solution containing 0.4 mg of boron/100 g body wt. The serum decay of boron was followed and found to be monophasic. The data were interpreted according to a one-compartment open model. The appropriate pharmacokinetic parameters were estimated as follows: absorption half-life, t1/2a=0.608+/-0.432 h; elimination half-life, t1/2=4.64+/-1.19 h; volume of distribution, Vd = 142.0+/-30.2 ml/100 g body wt.; total clearance, Ctot=0.359+/-0.0285 ml/min per 100 g body wt. The maximum boron concentration in serum after administration (Cmax) was 2.13+/-0.270 mg/l, and the time needed to reach this maximum concentration (Tmax) was 1.76+/-0.887 h. Our results suggest that orally administered boric acid is rapidly and completely absorbed from the gastrointestinal tract into the blood stream. Boric acid in the intravascular space does not have a strong affinity to serum proteins, and rapidly diffuses to the extravascular space in proportion to blood flow without massive accumulation or binding in tissues. The main route of boron excretion from the body is via glomerular filtration. It may be inferred that there is partial tubular resorption at low plasma levels. The animal model is proposed as a useful tool to approach the problem of environmental or industrial exposure to boron or in cases of accidental acute boron intoxication.

In vivo percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in humans: a summary.

Literature from the first half of this century reports concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry, which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax, and disodium octaborate tetrahydrate (DOT) in biological matrices. This made it possible, in the presence of comparatively large natural dietary boron intakes for the in vivo segment of this study, to quantify the boron passing through skin. Human volunteers were dosed with 10B-enriched boric acid, 5.0%, borax, 5.0%, or disodium octaborate tetrahydrate, 10% in aqueous solutions. Urinalysis, for boron and changes in boron isotope ratios, was used to measure absorption. Boric acid in vivo percutaneous absorption was 0.226 (SD = 0.125) mean percent dose, with flux and permeability constant (Kp) calculated at 0.009 microg/cm2/h and 1.9 x 10(-7) cm/h, respectively. Borax absorption was 0.210 (SD = 0.194) mean percent dose, with flux and Kp calculated at 0.009 microg/cm2/h and 1.8 x 10(-7) cm/h, respectively. DOT absorption was 0.122 (SD = 0.108) mean percent, with flux and Kp calculated at 0.01 microg/cm2/h and 1.0 x 10(-7) cm/h, respectively. Pretreatment with the potential skin irritant 2% sodium lauryl sulfate had no effect on boron skin absorption. These in vivo results show that percutaneous absorption of boron, as boric acid, borax, and disodium octaborate tetrahydrate, through intact human skin is low and is significantly less than the average daily dietary intake. This very low boron skin absorption makes it apparent that, for the borates tested, the use of gloves to prevent systemic uptake is unnecessary. These findings do not apply to abraded or otherwise damaged skin.

In vitro percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in human skin: a summary.

Literature from the first half of this century reports concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax and disodium octaborate tetrahydrate (DOT) in biological matrices. In vitro human skin percent doses of boric acid absorbed were 1.2 for a 0.05% solution, 0.28 for a 0.5% solution, and 0.70 for a 5.0% solution. These absorption amounts translated into flux values of, respectively, 0.25, 0.58, and 14.58 microg/cm2/h, and permeability constants (Kp) of 5.0 x 10(-4), 1.2 x 10(-4), and 2.9 x 10(-4) cm/h for the 0.05%, 0.5%, and 5.0% solutions. The above in vitro doses were at infinite, 1000 microL/cm2 volume. At 2 microL/cm2 (the in vivo dosing volume), flux decreased some 200-fold to 0.07 microg/cm2/h and Kp of 1.4 x 10(-6) cm/h, while percent dose absorbed was 1.75%. Borax dosed at 5.0%/1000 microL/cm2 had 0.41 percent dose absorbed, flux at 8.5 microg/cm2/h, and Kp was 1.7 x 10(-4) cm/h. Disodium octaborate tetrahydrate (DOT) dosed at 10%/1000 microL/cm2 was 0.19 percent dose absorbed, flux at 7.9 microg/cm2/h, and Kp was 0.8 x 10(-4) cm/h. These in vitro results from infinite doses (1000 microL/cm2) were a 1000-fold greater than those obtained in the companion in vivo study. The results from the finite (2 microL/cm2) dosing were closer (10-fold difference) to the in vivo results. General application of infinite dose percutaneous absorption values for risk assessment is questioned by these results.

Comparative toxicology of borates.

Inorganic borates, including boric acid, Na, ammonium, K, and Zn borates generally display low acute toxicity orally, dermally, and by inhalation. They are either not irritant or mild skin and eye irritants. Exceptions owing to physiochemical properties do occur. Longer-term toxicological studies have been reported mainly on boric acid or borax where the properties are generally similar on an equivalent boron (B) basis. The critical effects in several species are male reproductive toxicity and developmental toxicity. The doses that cause these effects are far higher than any levels to which the human population could be exposed. Humans would need to consume daily some 3.3 g of boric acid (or 5.0 g borax) to ingest the same dose level as the lowest animal NOAEL. No effects on fertility were seen in a population of workers exposed to borates or to a population exposed to high environmental borate levels. There is remarkable similarity in the toxicological effects of boric acid and borax across different species. Other inorganic borates that simply dissociate to boric acid are expected to display similar toxicity, whereas those that do not dissociate simply to boric acid may display a different toxicological profile.

Radiobiological evidence suggesting heterogeneous microdistribution of boron compounds in tumors: its relation to quiescent cell population and tumor cure in neutron capture therapy.

PURPOSE: The heterogeneous microdistribution of boron compounds in tumors and its significance on tumor cure were examined by a radiobiological procedure. The role of quiescent (Q) cells in tumor was especially investigated. METHODS AND MATERIALS: 10B-enriched paraboronophenylalanine (BPA) and mercaptoundecahydrododecaborate (BSH) were administered to SCCVII tumor bearing C3H/He mice by intragastric and i.v. injections, respectively. The continued effects of these boron compounds with thermal irradiations were studied by using colony formation and tumor control assays. Their effects on Q cells were also analyzed by the combined method of micronucleus frequency assay and an identification of proliferating (P) cells by BUdR and anti-BUdR monoclonal antibody. RESULTS: 10B-concentration after BPA (1,500 mg/kg) and BSH (75 mg/kg) administration were 11 ppm at 3 h and 10.5 ppm at 30 min, respectively. Cell survival decreased exponentially with an increment of neutron fluence (phi). The exponential parts of the curves were: -InSF = -0.052+ 13.0x10(13)phi, -InSF = -0.032+7.68X10(-13)phi, and -InSF = -0.0005+2.68x10(-13)phi for BPA-BNCT, BSH-BNCT, and NCT alone, respectively. Fifty percent tumor control was obtained at the influence of 10.2 x 10(12) n/cm2 in BPA-BNCT. On the other hand, 11.4 x 10(12) n/cm2 of neutrons had to be delivered in BSH-BNCT. The normal nuclear division fraction defined as the cell fraction that did not express micronuclei at first mitosis after treatment was investigated. The surviving cell fraction and the normal nuclear division fraction were regarded as equal in NCT alone. However, the normal nuclear division factor following BPA-BNCT was greater than the surviving cell fraction, and the difference increased with an increase in neutron fluence. In Q cells, BSH-BNCT yielded higher micronucleus frequency than BPA-BNCT and NCT alone. The frequencies in Q cells following BPA-BNCT and NCT alone were almost same as that in total cell population after NCT alone. CONCLUSIONS: Our data suggested that BPA distributed in tumors hetergeneously. Q cells especially might not accumulate BPA. To decrease the possible disadvantage of BPA-BNCT, the combination of BPA and BSH or other neutron capture element that emit particles with longer ranges, for example, gadolinium, would have to be investigated.

The relationship of blood- and urine-boron to boron exposure in borax-workers and usefulness of urine-boron as an exposure marker.

Daily dietary-boron intake and on-the-job inspired boron were compared with blood- and urine-boron concentrations in workers engaged in packaging and shipping borax. Fourteen workers handling borax at jobs of low, medium, and high dust exposures were sampled throughout full shifts for 5 consecutive days each. Airborne borax concentrations ranged from means of 3.3 mg/m3 to 18 mg/m3, measured gravimetrically. End-of-shift mean blood-boron concentrations ranged from 0.11 to 0.26 microgram/g; end-of-shift mean urine concentrations ranged from 3.16 to 10.72 micrograms/mg creatinine. Creatinine measures were used to adjust for differences in urine-specific gravity such that 1 ml of urine contains approximately 1 mg creatinine. There was no progressive increase in end-of-shift blood- or urine-boron concentrations across the days of the week. Urine testing done at the end of the work shift gave a somewhat better estimate of borate exposure than did blood testing, was sampled more easily, and was analytically less difficult to perform. Personal air samplers of two types were used: one, the 37-mm closed-face, two-piece cassette to estimate total dust and the other, the Institute of Occupational Medicine (IOM) sampler to estimate inspirable particulate mass. Under the conditions of this study, the IOM air sampler more nearly estimated human exposure as measured by blood- and urine-boron levels than did the sampler that measured total dust.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracoronal bleaching: concerns and considerations.

The history of intracoronal bleaching and the development of the walking bleach technique are reviewed. External cervical resorption associated with intracoronal bleaching is a serious sequela that has been reported in the literature. One explanation given for this phenomenon is that it results from an inflammatory process initiated by the presence of bleaching agents in the attachment apparatus. The basis for this conclusion is discussed. A review of published case reports on external cervical resorption associated with intracoronal bleaching revealed that: 100 per cent of the affected teeth had no intermediate dental base placed, 84 per cent were treated with a thermocatalytic technique, 80 per cent were bleached after the root canal sealer was fully set and 72 per cent had a history of trauma before bleaching. Based on these observations, it should be possible to safely bleach teeth intracoronally provided specific concerns and considerations are taken into account. These are: 1) the use of heat should be avoided; 2) an intermediate dental base should be placed with due respect to the attachment level; and 3) a base should be selected with due respect to its effectiveness in sealing tooth structure.