Selective uptake of p-borophenylalanine by undifferentiated thyroid carcinoma for boron neutron capture therapy.

Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of 10B-boronated compounds by some tumors, followed by irradiation with an appropriate neutron beam. The radioactive boron originated (11B) decays releasing 7Li, gamma rays and alpha particles, and these latter will destroy the tumor. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. In in vitro studies, the uptake of p-10borophenylalanine (BPA) by the UTC cell line ARO, primary cultures of normal bovine thyroid cells (BT), and human follicular adenoma (FA) thyroid was studied. No difference in BPA uptake was observed between proliferating and quiescent ARO cells. The uptake by quiescent ARO, BT, and FA showed that the ARO/BT and ARO/FA ratios were 4 and 5, respectively (p < 0.001). In in vivo studies, ARO cells were transplanted into the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg body weight) was injected intraperitoneally. The animals were sacrificed between 30 and 150 minutes after the injection. With 350 mg, tumor uptake was highest after 60 minutes and the tumor/normal thyroid and tumor/blood ratios were 3 and 5, respectively. When 600 mg/kg body weight BPA were administered, after 90 minutes the tumor/blood, tumor/normal thyroid, and tumor/distal skin ratios for 10B concentrations per gram of tissue were approximately 3, showing a selective uptake by the tumor. The present experimental results open the possibility of applying BNCT for the treatment of UTC.

The hamster cheek pouch as a model of oral cancer for boron neutron capture therapy studies: selective delivery of boron by boronophenylalanine.

Herein we propose and validate the hamster cheek pouch model of oral cancer for boron neutron capture therapy (BNCT) studies. This model serves to explore new applications of the technique, study the biology and radiobiology of BNCT, and assess the uptake of boron compounds and response of tumor, precancerous tissue, and clinically relevant normal tissues. These issues are central to evaluating and improving the therapeutic gain of BNCT. The success of BNCT is dependent on the absolute amount of boron in the tumor, and the tumor:blood and tumor:normal tissue boron concentration ratios. Within this context, biodistribution studies are pivotal. Tumors were induced in the hamsters with a carcinogenesis protocol that uses dimethyl-1,2-benzanthracene and mimics spontaneous tumor development in human oral mucosa. The animals were then used for biodistribution and pharmacokinetic studies of boronophenylalanine (BPA). Blood, tumor, precancerous pouch tissue surrounding tumor, normal pouch tissue, tongue, skin, cheek mucosa, palate mucosa, liver, and spleen, were sampled at 0-12 h after administration of 300 mg BPA/kg. The data reveal selective uptake of BPA by tumor tissue and, to a lesser degree, by precancerous tissue. Mean tumor boron concentration was 36.9 +/- 17.5 ppm at 3.5 h and the mean boron ratios were 2.4:1 for tumor:normal pouch tissue and 3.2:1 for tumor:blood. Higher doses of BPA (600 and 1200 mg BPA/kg) increased tumor uptake. Potentially therapeutic absolute boron concentrations, and tumor:normal tissue and tumor:blood ratios can be achieved in the hamster oral cancer model using BPA as the delivery agent.

Determination of inorganic and organic anionic arsenic species in water by ion chromatography coupled to hydride generation-inductively coupled plasma atomic emission spectrometry.

The development of an analytical methodology for the specific determination of arsenite, arsenate and the organic species monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), is described. The method is based on an ion chromatographic separation, coupled on-line to post-column generation of the gaseous hydrides by reaction with sodium tetrahydroborate in acidic medium. Detection and measurement were performed by inductively coupled plasma spectrometry operated in the atomic emission mode. Arsenic emission was monitored at 193.7 nm. Different types and sizes of anion-exchange columns, silica and polymeric, were tested using EDTA as eluent. Composition, acidity and flow-rate of the mobile phase were optimized in order to obtain the required resolution. Complete elution and resolution of the four species was achieved in about 6 min. Linear calibration curves were obtained in the 0.05-2 microg ml(-1) range for As(III), As(V) and MMA, and between 0.1 and 2.0 microg ml(-1) for DMA. The absolute limits of detection for 200-microl sample injections were in the ng range, with DMA the compound measured with less sensitivity. Results of the analyses of natural samples, such as river and ground waters spiked with the studied species, suggested that analyte recoveries might be dependent on the sample composition.

Evaluation of hydrogen line emission and argon plasma electron concentrations resulting from the gaseous sample injection involved in hydride generation-ICP-atomic emission spectrometric analysis.

The simultaneous injection of volatile hydride species and hydrogen gas, originating in reagent decomposition, was monitored during the operation of a continuous hydride generation manifold employed for the determination of trace arsenic by HG-ICP-AES. Line and background intensities as well as the FWHM of the hydrogen Hgamma and Hdelta lines were measured, and electron number densities (ne) estimated from Stark broadening of the line profiles. Results were compared with those obtained by conventional pneumatic injection of aqueous solutions. Overlapping with atomic nitrogen lines at 410 nm and 411 nm tends to distort the Hdelta line profile for the hydrogen-seeded plasma, rendering unreliable results. The N I lines seem to be quenched by the presence of water aerosol. More consistent results were obtained with the Hgamma line. When no solutions are pumped through the hydride generation manifold ("dry" plasma), the measured ne value was (1.57 +/- 0.22) x 10(15)cm(-3). Conversely, when the reducing reagent flow was replaced by pure water (corresponding to the injection of water vapor in equilibrium that is swept by the argon carrier gas passing through the phase separator), the electron concentration is 25% higher. In that case the ne value agrees between the experimental error with that obtained for a plasma in which a water aerosol is introduced at a flow rate of 1 mL/min. An enhancement of 52% relative is observed in ne when the system is operated under optimized conditions for arsine generation, employing sodium tetrahydroborate in acidic medium as reducing agent (i.e. hydrogen seeded plasma). It was also observed that the continuum emission near 410 nm for the hydrogen containing plasma correlates with the measured electron number density, suggesting that the background enhancement under hydride generation conditions may respond to the ion-electron recombination mechanism.