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PubMedDate not supplied

Concept for an off-line gain stabilisation method.

Conceptual ideas are presented for an off-line gain stabilisation method for spectrometry, in particular for alpha-particle spectrometry at low count rate. The method involves list mode storage of individual energy and time stamp data pairs. The 'Stieltjes integral' of measured spectra with respect to a reference spectrum is proposed as an indicator for gain instability. 'Exponentially moving averages' of the latter show the gain shift as a function of time. With this information, the data are relocated stochastically on a point-by-point basis.

Algorithms↗

PubMed2002

Evaluation of potential chelating agents for radium.

The alpha-particle-emitting radionuclide 223Ra (t(1/2) = 11.4 d) is of interest for use in targeted radionuclide therapy. In order to provide radium-labeled monoclonal antibodies, the development of a chelator binding radium in a stable fashion is required. As a part of the search for potentially useful radium chelators, the relative stability of 223Ra-chelates with linear and cyclic chelating agents was evaluated by means of competition extraction experiments.

Alpha Particles↗

PubMedDate not supplied

Validation of methods for the determination of radium in waters and soil.

This article describes the advantages and disadvantages of several analytical methods used to prepare the alpha-particle source. As a result of this study, a new method combining commercial extraction and ion chromatography prior to a final co-precipitation step is proposed. This method has been applied and validated on several matrices (soil, waters) in the framework of international intercomparisons. The integration of this method in a global procedure to analyze actinoids and radium from a single solution (or digested soil) is also described.

Alpha Particles↗

PubMed1999

The survival of monolayers of cells growing in clusters irradiated by 211At appended to the cell surfaces.

A model of cell survival is described for the case of closely packed clusters of cells growing in monolayers. For alpha-particle decays on the cell surfaces, it is shown that cross-firing between cells produces nonuniform dose distributions within the cluster and that cells in larger clusters are exposed on average to greater doses. The model is used to simulate the survival of SK-MEL-28 human melanoma cells labeled with different radiolabeled monoclonal antibodies. The survival data suggest that this cell line is more sensitive to high-LET radiation than previously thought.

Alpha Particles↗

PubMed1998

Lung cancer risk due to exposure to incorporated plutonium.

An epidemiological study has been carried out among 1,479 male workers who started working at the "Mayak" Production Association in 1948-1958 and were exposed to external gamma radiation and plutonium aerosols. Lung cancer mortality for the follow-up period 1948-1993 has been analyzed. No statistically significant association of lung cancer mortality and external gamma-ray dose has been revealed in the range of accumulated doses of 0.2-5.5 Gy. Association of lung cancer mortality and the dose of alpha-particle radiation to the lung is statistically significant. In the dose range below 30 Sv, this association can be described in terms of a linear nonthreshold function. Lifetime lung cancer risk in the dose range below 30 Sv is 1.21 x 10(-2)Sv(-1).

Adult↗

PubMed2005

Cytotoxicity of breast cancer cells overexpressing HER2/neu by 213Bi-Herceptin radioimmunoconjugate.

HER2 is the target of a new treatment for metastatic breast cancer using the humanized monoclonal antibody (MAb) trastuzumb (Herceptin). A novel alpha-particle emitting (213)Bi-Herceptin construct, targeting the HER2 extracellular domain on breast cancer cells, was produced by chelation and characterized in vitro in this study. We used Western blot and flow cytometry analysis to examine the expression of HER2 in a panel of established human metastatic breast cancer cell lines (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) MTS assay to evaluate the cytotoxicity and the TUNEL assay to analyze cellular apoptosis. Our results demonstrate that the human breast cancer cell lines BT-474 and SK-BR-3 express high levels of HER2 protein while MDA-231 expresses low levels of HER2. (213)Bi-Herceptin alpha conjugate (AC) was specifically cytotoxic to these cell lines in a HER2 level-dependent fashion, resulting in the cellular death through apoptosis. These results suggest that (231)Bi-Herceptin AC could be a novel agent for the treatment of breast cancer cell clusters or micro-metastases with high levels of HER2 expression.

Alpha Particles↗

PubMed1999

Comparative deterministic effects of inhaled, insoluble alpha- and beta-particle-emitting radionuclides in dogs.

This report compares the deterministic effects from an alpha-particle-emitting radionuclide, (239)PuO(2), and a beta-particle emitter, (144)Ce in fused aluminosilicate particles (FAP). The studies were conducted in beagle dogs of both genders exposed by inhalation to aerosols of the radionuclides. The initial lung burdens of (239)Pu and (144)Ce were determined by whole-body counting of the (169)Yb added to the plutonium aerosol during its preparation or the (144)Ce and its progeny (144)Pr. In addition, organ retention data were obtained from parallel serial sacrifice studies with the same aerosols. After exposure, the dogs were observed for health effects over their lifetime. The deterministic effects observed for both of these relatively insoluble aerosols were lymphopenia, fibrosis, atrophy of the lung-associated lymph nodes, and radiation pneumonitis. Due to the longer half-life of plutonium, the lymphopenia was more prolonged and the clinical course of the radiation pneumonitis more chronic than that resulting from cerium. The greater tissue penetration of the beta-particle emissions from the cerium resulted in more uniform dose distribution over the lung and the atria of the heart than from the alpha-particle emissions from plutonium.

Administration, Inhalation↗

PubMedDate not supplied

[The effects of the simultaneous combined irradiation of diploid yeast cells of different genotypes using radiation with different LETs].

Effects of simultaneous irradiation of diploid yeast cells with various genotypes with alpha-particles, gamma-rays or fast electrons were studied. When contribution of sparsely ionizing radiation to the overall dose is small (up to 25%) antagonism was observed, while at the 95% contribution there seems to be a tendency towards synergistic effect; at 50% contribution the results of the simultaneous combined irradiation do not contradict hypothesis on independent effect of radiation with different LET, which also implies a change in the RBE of simultaneous irradiation.

Alpha Particles↗

PubMed1981

Rbe of densely ionizing radiation for wild-type and radiosensitive mutants of yeast.

Survival curves were obtained for haploid and diploid yeasts, Saccharomyces cerevisiae, of wild-type strains and radiosensitive mutants exposed to gamma-rays and alpha-particles. A correlation between the values of the relative biological effectiveness (RBE) of high-LET radiation and cell-repair capacity was found. The difference in radiosensitivities of the wild-type diploid strain and homozygous rad mutants incapable of recovery was significantly higher after low-LET radiation than after high-LET radiation. Possible reasons for the observed radiation responses to low- and high-LET exposure of yeast cells with various genotype are discussed.

Alpha Particles↗

PubMed1989

Non-linear dose-effect curve for DNA double-strand breaks by low LET radiation: the effect of eluting buffer composition on the measurement of breaks by the filter elution technique.

Chinese hamster V79 cells were irradiated with 250 kVp X-rays and analysed for the presence of DNA double-strand breaks using filter elution. Changing the pH of the elution and lysis buffers from pH 9.6 to 7.2 leads to a decreased rate of elution of the DNA from the filters and a small difference in the dose-effect relationship obtained. In both cases the dose-effect curves were non-linear. When cells are irradiated with 238Pu alpha-particles a difference in the rate of elution of the DNA is also observed between the two pH values, although the dose-effect curves are linear. These findings suggest that there may be qualitative differences in the types of lesions being induced by low-LET radiation and being scored as dsb in the filter elution assay at pH 9.6. However, carrying out elution at pH 7.2 does not eliminate the nonlinear response measured after X-irradiation.

Alpha Particles↗

PubMed1996

SOS induction by low activity alpha sources: microdosimetric considerations.

The SOS response to alpha-radiation was measured using two Escherichia coli strains with differential repair capabilities. Monolayers of exponentially growing cells, placed on cellulose acetate filters, were exposed to an electrodeposited 252Cf alpha source to total doses from 46 to 165 cGy at a dose-rate of 0.8 cGy/min. A mean alpha energy of 2.9 MeV, with a corresponding LET of 133 keV/micrometer (for water) was attained by means of a filter placed between the bacterial culture and the radioactive source. Owing to the low fluences ranging from 0.013 to 0.037 alpha-particles/cell and short irradiation times, calculations of the estimated number of irradiated cells were done to obtain the total absorbed doses by the culture. The results show that in spite of the low doses, the damage was sufficient to induce the SOS function in one of the strains used (PQ37). Nevertheless in another strain IN88, lacking double strand break repair and which should be more sensitive, SOS induction could not be observed, probably due to the killing effect of the high LET radiation.

Alpha Particles↗

PubMed1989

Radiation dose factors for alpha-emitters in osteons and some considerations on dose non-uniformity ratios and relative distribution factors.

Dose factors for locations within a tissue-filled cylindrical cavity bounded by an infinite medium of bone labelled with an alpha-emitter are calculated by means of a Monte Carlo procedure. The calculational approach is general and allows us to determine dose factors for specific distances or target volumes defined by concentric cylinders, as well as various source geometries including surface sources, buried surface sources, infinite and bounded volume sources, and also comprises plane (trabecular) surfaces as a limiting case. Values for the dose factors and the contribution of cross-fire traversals are calculated mainly for 239Pu and 226Ra and a typical Haversian canal diameter of 30 microns in beagles and 70 microns in humans. Also tables are given that allow dose factors to be derived for the relevant range of alpha-particle energies, diameters and target distances. The dose non-uniformity factors (local dose rate/average skeletal dose rate) for 239Pu are 27.2 in humans and 14.0 in beagles. The corresponding values for 226Ra are in the ranges 1.18-1.26 (humans) and 0.90-0.97 (beagles) for a 222Rn retention between 10-30%. The relative distribution factors 239Pu/226Ra are 21.5-23.0 for humans and 14.5-15.6 for dogs. General expressions for calculating non-uniformity factors and relative distribution factors are derived and implications are discussed in the light of some experimental findings.

Alpha Particles↗

PubMed1999

A schema for estimating absorbed dose to organs following the administration of radionuclides with multiple unstable daughters: a matrix approach.

The dosimetry of alpha particle emitters requires that all decays, including those of unstable intermediates be included in the calculation. Such calculations are complicated by the potential differential biologic distribution of each of the intermediates. In this work we present a formalism which will account for the known biodistribution factors of the daughters and the resulting effective biodistribution which will depend upon the site at which the parent radionuclide decays. The number of decays or cumulated activity of a daughter radionuclide present in a particular tissue is estimated using a probability matrix which describes the likelihood of daughter decay in a particular tissue as a function of the decay site of the parent. An example of three initial compartments is provided to illustrate the use of this formalism. Such modeling may be used to evaluate the feasibility of using radionuclides whose decay includes alpha-emitting intermediates. Model validation and refinement will require an assessment of the fate of free, alpha-emitting intermediates in various biological milieus.

Alpha Particles↗

PubMed2004

William Henry Bragg in Adelaide: beginning research at a colonial locality.

This essay presents an account of W. H. Bragg's earliest research program in Australia during the years 1904-1907: a study of the behavior of alpha particles from radioactive decay. It is suggested that problems associated with distance and isolation played a pivotal role in Bragg's thinking and acting during this period and that his use of two "advocates," Ernest Rutherford and Frederick Soddy, was essential to the success of the program. It is further argued that this account supports a substantial amendment of the center-periphery model of colonial science to embrace a much closer attention to place and locality; that is, it supports a polycentric model (in which the center might still be prominent).

Alpha Particles↗

PubMed2004

The bystander response in C3H 10T1/2 cells: the influence of cell-to-cell contact.

Although radiation-induced heritable damage in mammalian cells was thought to result from the direct interaction of radiation with DNA, it is now accepted that biological effects may occur in cells that were not themselves traversed by ionizing radiation but are close to those that were. However, little is known about the mechanism underlying such a bystander effect, although cell-to-cell communication is thought to be of importance. Previous work using the Columbia microbeam demonstrated a significant bystander effect for clonogenic survival and oncogenic transformation in C3H 10T(1/2) cells. The present study was undertaken to assess the importance of the degree of cell-to-cell contact at the time of irradiation on the magnitude of this bystander effect by varying the cell density. When 10% of cells were exposed to a range of 2-12 alpha particles, a significantly greater number of cells (P < 0.0001) were inactivated when cells were irradiated at high density (>90% in contact with neighbors) than at low density (<10% in contact). In addition, the oncogenic transformation frequency was significantly higher in high-density cultures (P < 0.0004). These results suggest that when a cell is hit by radiation, the transmission of the bystander signal through cell-to-cell contact is an important mediator of the effect, implicating the involvement of intracellular communication through gap junctions.

Alpha Particles↗

PubMed2002

In vitro radiation-induced effects on rat tracheal epithelial cells. I) Different radiosensitivity of cell inactivation after alpha and gamma irradiations.

In order to compare the radiotoxicity of alpha- and gamma-irradiations, primary cultures of tracheal epithelial cells from two rat strains, Sprague Dawley (SD) and Wistar Furth/Fisher F344 (WF/Fi) rats, were irradiated with 241Am alpha-particles or 60 Co gamma-rays. The survival ratio for each of the two rat strain cells appeared to be statistically different after high-LET irradiation. WF/Fi rat cells were 1.7-times more radiosensitive than SD rat cells, whereas no difference was observed following low-LET irradiation. A comparison of the cell survival yielded RBEs of 2.8 and 4.5 for SD and WF/Fi rat cells, respectively. As previously observed, with increasing LET of particles, the cell-survival curves approximate an exponential function of the dose. On the contrary, for low-LET, the survival curves showed a marked initial shoulder. This in vitro cellular model, using epithelial cells of the upper airway, provides a suitable system to estimate the mechanism involved in radiosensitivity after high-LET irradiation. The responses to radiation-induced lethal effects within a same type of cell were dependent on the irradiation parameters, but might be modulated by the individual sensitivity under genetic or epigenetic factor controls.

Alpha Particles↗

PubMed1998

Calculation of boron neutron capture cell inactivation in vitro based on particle track structure and x-ray sensitivity.

The Monte-Carlo technique was used to perform quantitative microdosimetric model calculations of cell survival after boron neutron capture irradiations in vitro. The high energy 7Li and alpha-particles resulting from the neutron capture reaction 10B (n,alpha)7Li are of short range and are highly damaging to cells. The biophysical model of the Monte-Carlo calculations is based on the track structure of these a-particles and 7Li-ions and the x-ray sensitivity of the irradiated cells. The biological effect of these particles can be determined if the lethal effect of local doses deposited in very small fractional volumes of the cell nucleus is known. This lethal effect can be deduced from experimental data of cell survival after x-ray irradiation assuming a Poisson distribution for lethal events. The input data used in a PC-based computer program are the radial dose distribution inside the track of the released particles, cell survival after x-ray irradiation, geometry of the tumor cells, subcellular 10B concentration, and thermal neutron fluence. The basic concept of this Monte-Carlo computer model is demonstrated. Validations of computer calculations are presented by comparing them with experimental data on cell survival.

Alpha Particles↗

PubMed2004

Reconstruction of cluster distributions at 100% detection efficiency for a track-nanodosimetric counter through a Bayesian analysis.

A Bayesian unfolding has been applied to ionisation distributions due to 5.4 MeV alpha particles in a 20-nm site obtained using Monte Carlo simulations, taking into account different detection efficiency conditions. The ideal case of a target volume with uniform efficiency has been investigated to study the dependence of the reconstruction on prior distributions. A simplified approach has been used to treat the case of a target volume with non-uniformly distributed efficiency, like the sensitive volume of the track-nanodosimetric counter. Our results point out that Bayesian analysis provides a effective tool for reconstructing the true ionisation distributions, well beyond the maximum measured cluster size.

Algorithms↗