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PubMed1979

Elemental analysis of bone mineral by backscattering of alpha particles.

Backscattering of 2 MeV alpha particles has been applied for the first time to studies of the inorganic substances of human bone. Bone samples taken from the femoral shaft (dense bone) and iliac crest (spongy bone) of 18 cadavers were analysed for the calcium, phosphorus and oxygen content, after lyophilisation and heating for 1.5 h at 500 degrees C to remove water and organic material. The backscattering method produces a spectrum in which all the elements present in the sample except hydrogen can be seen at once. The reproducibility of the measurements was less than 2%. No previous studies were found in the literature of the measurement of elemental oxygen in bone samples. Ca/P ratios varied from 1.97 to 2.47, Ca/O ratios from 0.76 to 0.91 and P/O ratios from 0.34 to 0.41, the latter two being about 10--15% lower than expected if bone mineral were hydroxyapatite (Ca/O = 0.96 and P/O = 0.44). The results are consistent with previous work on Ca/P ratios but the low Ca/O and P/O ratios could not be explained without postulation of crystal or hydroxyl water in bone mineral. Support for the explanation was gained by differential gravimetric and thermal analysis.

Alpha Particles↗

PubMed1993

A model of cell inactivation by alpha-particle internal emitters.

Tumor-associated antibodies labeled with 131I and 90Y have been used in the treatment of malignant disease with some success. The use of alpha-particle-emitting radionuclides as radiolabels offers potential advantages over beta-particle sources. The short range in tissue (< 100 microns) and the high linear energy transfer associated with alpha-particle emitters will result in a more concentrated deposition of energy at the site of radionuclide decay. Thus, if radiolabeled antibodies can be bound to malignant cells specifically, a high differential cell killing can be achieved between the malignant and the normal cells. However, the energy deposition pattern will be strongly dependent upon the configuration of alpha-particle sources relative to the cells, and will consequently impact upon the dose-response characteristics. The purpose of this paper is to study distributions of energy deposition from alpha-particle-emitting radioimmunoconjugates distributed uniformly and nonuniformly around cells through theoretical modeling. Energy deposition spectra for cell nuclei are calculated and used to estimate the survival fraction by a simple biological model. We show that survival curves resulting from nonuniform distributions of alpha-particle-emitting radiolabeled antibodies can depart significantly from the classical exponential survival model applied to external alpha-particle beams. The survival curves may have initial slopes much steeper than those produced by a uniform distribution of sources, and they may also depart from linearity. Furthermore, the results of the modelling indicate how survival curves are dependent on the cell and radiolabel spacing. The results from our model compare reasonably well with published experimental data and can be used to facilitate the design and interpretation of radiobiological experiments.

Alpha Particles↗

PubMed2002

M-FISH analysis shows that complex chromosome aberrations induced by alpha -particle tracks are cumulative products of localized rearrangements.

Complex chromosome aberrations are characteristically induced after exposure to low doses of densely ionizing radiation, but little is understood about their formation. To address this issue, we irradiated human peripheral blood lymphocytes in vitro with 0.5 Gy densely ionizing alpha-particles (mean of 1 alpha-particle/cell) and analyzed the chromosome aberrations produced by using 24-color multiplex fluorescence in situ hybridization (M-FISH). Our data suggest that complex formation is a consequence of direct nuclear alpha-particle traversal and show that the likely product of illegitimate repair of damage from a single alpha-particle is a single complex exchange. From an assessment of the "cycle structure" of each complex exchange we predict alpha-particle-induced damage to be repaired at specific localized sites, and complexes to be formed as cumulative products of this repair.

Alpha Particles↗

PubMed2001

The relationship between the RBE of alpha particles and the radiosensitivity of different mutations of Chinese hamster cells.

The RBE of alpha-particles in different mutations of Chinese hamster cells was determined with the aim of identifying differences in the sensitivity to x-ray and alpha-particle-induced DNA damage. Two parental lines of Chinese hamster cells and four radiosensitive mutants were irradiated with different single doses of x-rays and alpha-particles and clonogenic cell survival was determined. Radiosensitivity to x-rays varied by a factor of 5 between the cell strains whereas sensitivity to alpha-particle irradiation was almost identical among all strains. The RBE is only determined by the sensitivity of the cells towards x-rays. Since cells with different defects of repair or cell cycle control have different radiosensitivities, we conclude that the effects of x-ray irradiation and the RBE are mostly determined by the activity of repair processes.

Alpha Particles↗

PubMed1996

Radioimmunotherapy with alpha-particle emitting radioimmunoconjugates.

Radionuclides which decay by the emission of alpha-particles are attractive for certain radioimmunotherapeutic applications. These include the treatment of lymphomas, compartmentally spread malignancies such as ovarian cancer and neoplastic meningitis, and micrometastatic disease. Two alpha-emitting radionuclides of interest for this purpose are 212Bi (60.6 min half life) and 211At (7.2 hr half life). Compared with the beta-emitters commonly used for radiotherapy, the alpha-particles of 212Bi and 211At are of higher energy, much shorter range (less than 100 microm), and considerably higher linear energy transfer. Preliminary results obtained in a variety of in vitro systems and in vivo models have documented the exquisite toxicity of alpha-particles and have established a basis for initiating radiotherapy trials in humans with monoclonal antibodies labeled with alpha-emitting radionuclides.

Alpha Particles↗

PubMed2004

Interaction of alpha particles at the cellular level--implications for the radiation weighting factor.

Since low dose effects of alpha particles are produced by cellular hits in a relatively small fraction of exposed cells, the present study focuses on alpha particle interactions in bronchial epithelial cells following exposure to inhaled radon progeny. A computer code was developed for the calculation of microdosimetric spectra, dose and hit probabilities for alpha particles emitted from uniform and non-uniform source distributions in cylindrical and Y-shaped bronchial airway geometries. Activity accumulations at the dividing spur of bronchial airway bifurcations produce hot spots of cellular hits, indicating that a small fraction of cells located at such sites may receive substantially higher doses. While presently available data on in vitro transformation frequencies suggest that the relative biological effectiveness for alpha particles ranges from about 3 to 10, the effect of inhomogeneous activity distributions of radon progeny may slightly increase the radiation weighting factor relative to a uniform distribution. Thus a radiation weighting factor of about 10 may be more realistic than the current value of 20, at least for lung cancer risk following inhalation of short-lived radon progeny.

Air Pollutants, Radioactive↗

PubMed1994

Alpha particles are extremely damaging to developing hemopoiesis compared to gamma irradiation.

Estimates of risk of stochastic effects from contamination with alpha-particle-emitting radionuclides are based on equivalent doses which take into account the RBE of the high-LET radiation. ICRP has recommended a dose-weighting factor, wR, of 20 for alpha-particle radiation. It is assumed that the RBEs for deterministic effects are considerably less than those for stochastic effects. However, the offspring of mice injected with 30 Bq g-1 239Pu at 13 days gestation develop a persistent deficit in hemopoietic stem cells which is primarily the result of damage to their regulatory microenvironment. Their spatial distribution in the marrow is also perturbed, and recent observations on those mice suggested a considerably higher factor than 20. To define a more realistic RBE for hemopoiesis, the effects of external gamma irradiation during the fetal development period have been compared directly with those of 239Pu incorporated via placental transfer on the development of hemopoietic tissue. Pregnant mice were irradiated with 60Co gamma rays (a) continuously from day 13 of gestation to birth at 0.15 or 0.6 Gy/day; (b) six repeated acute doses (0.6 Gy/min) at 0.1 or 0.3 Gy from day 13 of gestation; (c) one acute dose of 0.6 or 1.8 Gy on day 15 of gestation. The spatial distribution of hemopoietic stem cells in 8-week-old offspring was then determined and compared to that resulting from alpha-particle irradiation. In each case, the higher dose was required to match the results for alpha particles, suggesting an RBE for developing hemopoiesis of 250-360 compared to a continuous gamma-ray dose and a rather lower value of 130-180 compared to a single acute dose of gamma rays. This contrasts greatly to values for direct irradiation of the stem cells but argues that the effective RBE, measured for long-term effects in vivo, is the more realistic. It is concluded that an all-embracing factor can be grossly misleading in the specification of protection guidelines and can greatly underestimate the risks of exposure to alpha particles.

Alpha Particles↗

PubMed2004

Relative sensitivities of repair-deficient mammalian cells for clonogenic survival after alpha-particle irradiation.

The clonogenic survival of cells of the radiation-sensitive hamster cell lines irs1, irs2, irs3 and xrs5, representing different DNA repair pathways, was compared to that of their parent lines after alpha-particle irradiation. Measurements of nuclear area were made to calculate the probability of surviving a single alpha-particle traversal, the average number of lethal lesions per track and per unit dose, along with the "intrinsic radiosensitivity" of these cells, allowing for the potential of multiple lethal lesions per traversal. For all cell lines studied, alpha particles were found to be more biologically effective per unit absorbed dose than X rays at inducing cell inactivation. The repair-deficient cells showed an enhanced sensitivity to alpha particles compared to their parent line, but the degree of enhancement was less than for X rays. The reduction in additional sensitivity for alpha-particle irradiation was shown not to be due predominantly to differences in cell geometry limiting the probability of a cell nucleus being traversed. The results suggest that both the nonhomologous end-joining pathway and to a lesser extent the homologous recombination repair pathway play a role in successful repair of alpha-particle-induced damage, although a large proportion of damage is not repaired by either pathway.

Alpha Particles↗

PubMed1994

Neoplastic transformation dose response of oncogene-transfected rat embryo cells by gamma rays or 6 MeV alpha particles.

We measured a dose-response relationship for induction of neoplastic transformation by 6 MeV alpha particles and 137Cs gamma rays in REC:myc and REC:ras cells, that is, rat embryo cells (REC) transfected with the c-myc or the Ha-ras oncogenes. The 6 MeV alpha particles simulated 222Rn emissions for risk assessment relative to low-LET radiations. The dose of gamma rays was approximately twice that of alpha particles for a neoplastic transformation frequency of 10(-3). The survival of the REC cells containing oncogenes was comparable to that of the commonly used C3H 10T1/2 cells for the same dose, but the former were more refractory to radiation-induced neoplastic transformation. Neoplastic transformation frequency measured in REC cells was 3 times lower than those typically measured in C3H 10T1/2 cells at a gamma-ray dose of 6 Gy, and 5-10 times lower at an alpha-particle dose of 3 Gy.

Alpha Particles↗

PubMed2003

Characterization of an alpha-particle irradiator for individual cell dosimetry measurements.

A computer-controlled, alpha-particle irradiator is described that allows for the measurement of the number and location of alpha-particle hits to individual cell nuclei, and subsequent scoring of cell survival. Cells are grown on a track-etch material (LR 115) and images are obtained of the cells prior to irradiation. The cells are then irradiated from below by a planar, collimated Am-241 source. The exposure time is varied so that the average number of hits to cell nuclei ranges from 0 to 3. After cell survival has been scored, images of the etched material are obtained and spatially registered to the original cell images. The etched images and cellular images are superimposed allowing for the determination of the number and position of hits to individual cell nuclei. This paper characterizes the irradiator including the energy and fluence of the incident alpha particles. Additionally, we describe the sources of uncertainty associated with this experiment, including the cell dish repositioning and cell migration during scanning and irradiation.

Alpha Particles↗

PubMed2000

Determination of the absolute alpha-particle emission probabilities of 237Np

In the framework of the EUROMET project No. 416, decay scheme data of 237Np were measured by alpha-particle spectrometry. Emission probabilities of alpha-particles and gamma-rays were determined in the past at IRMM. After improvements of the detector system and the electron bending magnet the alpha-particle measurements have been repeated. As a result, the absolute emission probabilities of 20 alpha-particle transitions were obtained with a significant lower uncertainty. Among those transitions already known, five new were found.

Journal Article↗

PubMed1991

A versatile plutonium-238 irradiator for radiobiological studies with alpha-particles.

A versatile irradiator has been constructed for in vitro irradiation of mammalian cells with alpha-particles of well-defined energy, LET, direction, dose and dose rate. It is based on approximately 1.2 x 10(9) Bq of 238Pu (on a platinum disc) contained in a He-filled chamber. In a standard configuration, monolayers of cells grown in 10 Hostaphan-based dishes are irradiated with 3.26 +/- 0.22 MeV alpha-particles (LET 121 keV microns-1) at selectable dose rates from approximately 2 Gy min-1 down to less than 10(-4) Gy min-1 (i.e. fluence rates of 1 x 10(7) cm-2 min-1 to 3 x 10(2) cm-2 min-1). Single dishes can be irradiated at dose rates up to 24 Gy min-1 (fluence rate 1 x 10(8) cm-2 min-1). Incident energy and LET can be varied from 0.8 to 4.2 MeV and 266 to 102 keV microns-1, respectively. The irradiator has full incubation and gassing facilities for protracted irradiations. The irradiator is particularly suitable for in vitro analytical studies of the biological effects of alpha-particles of energies and LETs similar to those which cells may receive in vivo from radionuclides such as radon and the actinides. It has been used successfully for investigations of a variety of alpha-particle-induced effects in different cell types irradiated either as attached monolayers or as very thin suspensions.

Alpha Particles↗

PubMed1996

Analysis of chromosome aberrations in human peripheral lymphocytes induced by in vitro alpha-particle irradiation.

Irradiation of human lymphocytes by alpha-particles under different conditions has been seen to be substantially more effective in the induction of dicentric chromosomes than irradiation by gamma-rays. However, the relative biological effectiveness (RBE) determined in these studies differed by a factor of more than 10. These variations in RBE are likely to be due in part to differing exposure conditions. Therefore, a technique designed to insure uniformity of irradiation was developed in the present study, and complications due to the cell cycle kinetics were controlled. After stimulation with phytohaemagglutinin (PHA), separated lymphocytes were allowed to attach for 3 h to the thin foil bottom of an irradiation chamber. Cell monolayers were exposed with alpha-particles from Am. Strong over-dispersion was noted for the cell-to-cell variance of the number of dicentrics. The dose response of dicentrics was linear, with a yield of 0.27 dicentrics per cell and per Gy. This corresponds to a low dose RBE of 15 relative to Cs gamma-ray exposure under the same experimental conditions.

Alpha Particles↗

PubMed1998

Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation.

We have demonstrated chromosomal instability in the clonal descendants of hemopoietic stem cells after irradiating murine bone marrow with alpha-particles. However, because cells that are irradiated by alpha-particles are defined by a Poisson distribution of individual particle traversals, there is an inevitable proportion of unirradiated cells in the surviving population. The calculated expected proportions of irradiated and nonirradiated cells indicate that the number of clonogenic cells transmitting chromosomal instability is greater than the number expected to be hit and survive. To investigate further this discrepancy, we studied the effects of interposing a grid between the cells and the alpha-particle source so that the surviving population consists predominantly of untraversed stem cells. Comparison with the same irradiation conditions without the grid reveals that the same level of instability is induced. The data confirm that alpha-particles induce chromosomal instability but instability is demonstrated in the progeny of nonirradiated stem cells and must be due to unexpected interactions between irradiated and nonirradiated cells. This untargeted effect has important implications for mechanistic studies of radiation action and for assessment of radiation risk.

Abnormalities, Radiation-Induced↗

PubMed2002

Measurements of alpha particle energy using nuclear tracks in solids methodology.

In this paper we present a method for the measurement of alpha particle energy using polycarbonate materials as nuclear track detectors (NTDs). This method is based on the interaction of the radiation with the solid-state materials, using the relationship between the energy deposited in the material by the ionising particle and the track developed after an established chemical process. The determination of the geometrical parameters of the formed track, such as major axis, minor axis and overall track length, permit determination of the energy of the alpha particle. The track analysis is performed automatically using a digital image system, and the data are processed in a PC with commercial software. In this experiment 148Gd, 238U, 230Th, 239Pu and 244Cm alpha particle emitters were used. The values for alpha particle energy resolution, the linear response to energy, the confidence in the results and the automatisation of the procedure make this method a promising analysis system.

Alpha Particles↗

PubMed1991

Mutations induced by ionizing radiation in a plasmid replicated in human cells. II. Sequence analysis of alpha-particle-induced point mutations.

The human shuttle plasmid pZ189, containing the Escherichia coli supF gene as the mutational target, was irradiated in vitro with 210Po alpha particles and transfected into human lymphoblastoid cells. Plasmids which were replicated in human cells were recovered and those containing mutant supF genes were isolated by phenotypic screening in E. coli. The mutations were characterized by sequencing the tRNA gene. The mutant frequency increased linearly with the alpha-particle dose and, at 259 Gy, it was 16 times (0.29%) that observed in unirradiated controls (0.018%). The distribution of alpha-particle-induced point mutations was highly nonrandom and similar to that observed in the unirradiated or X-irradiated plasmid DNAs. The majority of the mutations were G.C----A.T transitions and occurred selectively at most 5'-TC (3'-AG) and 5'-CC (3'-GG) sequences. For the unirradiated control DNA, these mutations at C's (G's) were preferentially located in the nontranscribed strand, similar to the observation previously made for mutations in X-irradiated DNA. Such a strand bias was not observed for mutations in the alpha-particle-irradiated DNA. The data suggest that, although similar types of point mutations are induced in unirradiated, X-irradiated, and alpha-particle-irradiated DNAs, the mechanisms of their induction and the exact nature of the lesions involved may be quite different.

Alpha Particles↗

PubMed1998

Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia.

The high linear energy transfer, alpha-particle-emitting radionuclide astatine-211 (211At) is of interest for certain therapeutic applications; however, because of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous tracer distribution is critical. Hyperthermia may enhance the therapeutic efficacy of alpha-particle endoradiotherapy if it can improve tracer distribution. In this study, we have investigated whether hyperthermia increased the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour spheroids with a radius (approximately 100 microm) greater than the range of 211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6 reactive with the extracellular matrix antigen tenascin was added to spheroids grown from the D-247 MG human glioma cell line at activity concentrations ranging from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125 and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For groups receiving hyperthermia, no increase in cytotoxicity was seen compared with normothermic controls at any activity concentration. These results and those from autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no significant effect on the uptake or distribution of this antitenascin MAb in D-247 MG spheroids.

Alpha Particles↗

PubMed1994

TASTRAK spectroscopy of polonium-210 alpha-particle activity at bone surfaces: evidence for a concentrated surface deposit less than 3 microns deep.

The technique of alpha-particle spectroscopy by CR-39 type TASTRAK plastic has been used to study the depth distribution of natural alpha-particle emitters at the surface of human bone. The predominant component of this alpha-particle activity was 210Po supported by 210Pb, although a smaller activity of 226Ra was also detected. Autopsy samples of human femur and cranium were obtained from subjects age 63 to 86. Both cortical and trabecular surfaces were analyzed. The results indicate that 210Pb-supported 210Po is concentrated at the surfaces of human bone from elderly subjects, in a narrow band 3 microns deep or less, by a factor of about four. As a result, the alpha-particle dose to the nuclei of cells lining bone surfaces is around 1.8 times greater than that calculated for a uniform volume distribution. Polonium-210 activity indicates the distribution of 210Pb, and of stable lead, received by continuous intake throughout life at a very low level. A persistent bone surface concentration of lead and other osteotropic metals may be associated with the hypermineralized layer about 1 micron thick which occurs at the surface of resting bone mineral.

Aged↗