Microdosimetric Modeling of Biological Effectiveness for Boron Neutron Capture Therapy Considering Intra- and Intercellular Heterogeneity in 10B Distribution.

We here propose a new model for estimating the biological effectiveness for boron neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity in 10B distribution. The new model was developed from our previously established stochastic microdosimetric kinetic model that determines the surviving fraction of cells irradiated with any radiations. In the model, the probability density of the absorbed doses in microscopic scales is the fundamental physical index for characterizing the radiation fields. A new computational method was established to determine the probability density for application to BNCT using the Particle and Heavy Ion Transport code System PHITS. The parameters used in the model were determined from the measured surviving fraction of tumor cells administrated with two kinds of 10B compounds. The model quantitatively highlighted the indispensable need to consider the synergetic effect and the dose dependence of the biological effectiveness in the estimate of the therapeutic effect of BNCT. The model can predict the biological effectiveness of newly developed 10B compounds based on their intra- and intercellular distributions, and thus, it can play important roles not only in treatment planning but also in drug discovery research for future BNCT.

Growth aspects of photochemically synthesized silver triangular nanoplates.

Aspects of the growth mechanism of silver triangular nanoplates by photochemical synthesis were addressed by detailed characterization using ultraviolet-visible spectroscopy, electron microscopies, and atomic force microscopy. The quantitative characterization of their size and thickness during the reaction showed that both increase with time as well as the aspect ratio. Samples irradiated by different wavelengths showed that the size of the nanoplates can be controlled by the incident wavelength and it is responsible for the increase of the aspect ratio, but the thickness seems to be determined by the conditions of the initial seeds. It was also found that irradiation with wavelength out of resonance with the surface plasmon of the initial seeds leads to a slower kinetics. The results suggested that rational exploration of the synthesis parameter such as the type of the initial seeds in combination with the wavelength irradiation may lead to a broader type of particles already obtained by this method.

A radioluminescence study of spectral and dose characteristics of common luminophors.

Many synthetic materials are used as thermoluminescence dosemeters for the measurement of the absorbed dose from ionising radiation sources. A part of the absorbed energy leads to a prompt luminescence (radioluminescence, abbreviated RL) which dose behaviour mainly corresponds with the densitity of charge carriers in the respective traps or recombination sites. The RL reported in this study was stimulated using two 137Cs sources with activities of 3.7 MBq (spectral measurements) or 5 MBq (dosimetry studies), respectively, and was recorded steadily during stimulation. This presentation gives a comprehensive survey of the spectral and dose dependent RL properties of a number of luminescent materials like LiF:Mg,Ti, Al2O3:C, CaSO4:Dy, CaF2:Mn, Li2B4O7:Mn, BeO and ZnS:Ag. The spectral and dose dependent results were compared with thermoluminescence as well as other RL studies.

Boron neutron capture therapy of brain tumors: enhanced survival following intracarotid injection of either sodium borocaptate or boronophenylalanine with or without blood-brain barrier disruption.

The purpose of the present study was to determine whether the efficacy of boron neutron capture therapy could be enhanced by means of intracarotid (i.c.) injection of sodium borocaptate (BSH) or boronophenylalanine (BPA) with or without blood-brain barrier disruption (BBB-D). For biodistribution studies, F98 glioma-bearing rats were injected i.v. or i.c. with either BSH (30 mg of boron/kg of body weight) or BPA (24 mg of boron/kg of body weight) with or without mannitol-induced, hyperosmotic BBB-D and killed 2.5 h later. The highest tumor boron concentrations for BSH and BPA were attained following i.c. injection with BBB-D (48.6 and 94.0 microg/g, respectively) compared to i.c. (30.8 and 42.7 microg/g) and i.v. injection (12.9 and 20.8 microg). Using the same doses of BSH and BPA, therapy experiments were initiated 14 days after intracerebral implantation of F98 glioma cells. Animals were irradiated 2.5 h after i.v. or i.c. administration of the capture agent with or without BBB-D using a collimated beam of thermal neutrons at the Brookhaven Medical Research Reactor. The median survival times of rats given BSH or BPA i.c. were 52 and 69 days, respectively, for rats with BBB-D; 39 and 48 days for rats without BBB-D; 33 and 37 days for i.v. injected rats; 29 days for irradiated controls; and 24 days for untreated controls. i.c. injection of either BSH or BPA resulted in highly significant enhancement (P = 0.01 and P = 0.0002, respectively) of survival times compared to i.v. injection, and this was further augmented by BBB-D (P = 0.02 and P = 0.04, respectively) compared to i.c. injection. Normal brain tissue tolerance studies were carried out with non-tumor-bearing rats, which were treated in the same way as tumor-bearing animals. One year after irradiation, the brains of these animals showed only minimal radiation-induced changes in the choroid plexus, but no differences were discernible between irradiated controls and those that had BBB-D followed by i.c. injection of either BSH or BPA. Our data clearly show that the route of administration, as well as BBB-D, can enhance the uptake of BSH and BPA, and, subsequently, the efficacy of boron neutron capture therapy.

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.

Contrast effects in photoelectron microscopy; UV dose-dependent quantum yields of biological surface components.

The relative brightness of photoelectron microscopy images as a function of exposure to UV light has been determined from model systems representative of biological cell surface components. Quantitative data for amino acid homopolymers, yields. The photoelectron quantum yields, increase substantially over the initial values. For example, the quantum yields fo poly-L-tyrosine at 200 nm is initially about 5 X 10(-8) electron/incident photon. The quantum yield increases with 254 nm irradiation, leveling off at about 5 X 10(-4) electrons/incident photon after a dose of 3 X 10(21) quanta cm-2. Pre-irradiation of poly-L-tyrosine in the presence of certain chemical agents, for example, the Lewis base diborane (B2H6), results in a substantial reduction of the dose-dependent increase in quantum yield. Exposure to the reducing agent stannane (SnH4) essentially eliminates the effect. These chemical treatments provide methods of controlling the UV dose-dependent effects in the photoelectron images.