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PubMed1990

External exposure estimates for individuals near the Nevada Test Site.

Individuals living near the Nevada Test Site were exposed to both beta and gamma radiations from fission products and activation products resulting from the atmospheric testing of nuclear devices. These exposures, and the resultant doses, were functions of the amount of material deposited, the time of arrival of the debris, and the amount of shielding afforded by structures. Results are presented for each of nine generic life-styles. These are representative of the living patterns of people residing in the area. For each event at each location for which data exist, a representative of each life-style was closely followed for 30 d. The results of these detailed calculations were then extrapolated to the present, employing a stochastic model. Results displayed are the geometric means and standard deviations derived from 25 independent determinations of the various quantities shown. For each determination, required parameters were randomly selected from appropriate distributions. Calculations yielded estimates for: 1) whole-body and skin dose due to gamma rays from material on the ground; 2) skin dose due to beta particles from material deposited directly on the skin; and 3) skin dose due to beta particles from material deposited on the ground. Organ dose estimates were established from the whole-body dose using appropriate conversion factors. For the homemaker life-style, the uterus dose was also calculated as a function of time for 9 mo. This assisted in estimating fetal dose as a function of gestation.

Beta Particles↗
PubMed1986

Granuloma and plasma cell formation induced by the subcutaneous implantation of beta-whitlockite particles.

In this paper, the formation of a granuloma following subcutaneous implantation of beta-whitlockite powder is described. The implants were removed after 3, 5 and 7 wk and examined histologically. In the granuloma giant cells, macrophages, lymphocytes and plasma cells are present. The presence of plasma cells indicates that not only inflammation occurs, but that an immunoresponse also takes place. Resorption and phagocytosis of particles was observed and the particles were found in the regional lymph nodes after 7 wk. beta-Whitlockite powder induces an inflammation and both a cellular and a humoral immunological response, when implanted subcutaneously.

Animals↗
PubMed2001

Therapy of disseminated B-cell lymphoma xenografts in severe combined immunodeficient mice with an anti-CD74 antibody conjugated with (111)indium, (67)gallium, or (90)yttrium.

A radiolabeled antibody (Ab) to CD74 (the MHC class II invariant chain, Ii) was shown previously to effectively kill human B-lymphoma cells in vitro. Conjugates with both Auger electron and beta-particle emitters were able to kill cells, but the former displayed less nonspecific toxicity in the in vitro assay used. In this report, we have extended the studies to an in vivo model of tumor growth. The human B-cell lymphoma Raji was injected i.v. into severe combined immunodeficient mice, and radiolabeled Abs were injected at various times after tumor inoculation. The maximum tolerated dose (MTD), as well as lower doses, was tested. Tumor growth was monitored by hind-leg paralysis. With a 3-5-day interval before Ab injection, anti-CD74 conjugated to either (111)In or (67)Ga, at a dose of 240-350 microCi/mouse, produced a strong therapeutic effect, with greatly delayed tumor growth, and many of the treated mice were tumor free for >6 months. Control mice became paralyzed in 16-24 days, uniformly. Treatment at later time points (9-day interval) had little therapeutic effect. The MTD was required for optimal therapy. With the beta-particle emitter (90)Y, the MTD was much less, 25 microCi/mouse, and at this dose there was only a weak therapeutic effect. In conclusion, the data suggest that low-energy electrons are more effective than beta-particles in this model system. These results may be applicable to humans, particularly in the case of micrometastatic disease. This approach may also be effective with other Abs that accrete in large amounts.

Animals↗
PubMed1994

Use of bremsstrahlung radiation to monitor Y-90 tumor and whole body activities during experimental radioimmunotherapy in mice.

BACKGROUND: Large differences in uptake between tumors, even for the same size, frequently observed in clinical and experimental radioimmunotherapy (RAIT), make monitoring of uptake in individual tumors imperative in comparing protocols. 90Y, widely-used for RAIT, emits no gamma radiation and absorption of the beta particle in tissue makes its detection unsuitable for in vivo monitoring. We tested whether bremsstrahlung radiation, produced when betas are decelerated by nuclei, could be used to monitor tumor uptake. METHODS: Subcutaneous human LS174T colon carcinoma tumors were grown in the upper thigh of nude mice and labeled antibody injected intracardially. With the tumor placed in the 2 cm-diameter aperture in a lead collimator, photons with energies from 100 to 200 keV transmitted through plastic, which absorbed the beta particles, were counted to maximize shielding from the rest of the body. The contribution of the normal tissues was subtracted by counting the non-tumor-bearing leg in the same position. Excretion was calculated from whole body activity determined by removing the collimator, placing the mouse in a syringe surrounded by tissue-equivalent material 10 cm from the detector, and counting photons between 200 and 740 keV to minimize the effect of tissue attenuation. RESULTS: For tumors larger than 0.14 gm, a good correlation was obtained between the in vivo bremsstrahlung measurements and the measurements on excised tumors in a calibrated well counter. Similar excretion rates observed in all the animals suggested that the whole body counting was accurate. CONCLUSIONS: Bremstrahlung detection appears feasible and reliable for monitoring both tumor and whole body activities.

Animals↗
PubMed1999

Particles binding beta(2)-integrins mediate intracellular production of oxidative metabolites in human neutrophils independently of phagocytosis.

Complement-opsonised particles are readily ingested by human neutrophils through a complement receptor-mediated process leading to phagolysosome fusion and production of oxidative metabolites. To investigate the complement receptor 3 (CR3)-associated signal system involved, cells were challenged with protein A-positive, heat-killed Staphylococcus aureus to which antibodies with specificity for the subunits of the beta(2)-integrins, i.e. anti-CD11b (the alpha subunit of CR3) and anti-CD18 (the beta subunit of CR3), were bound through their Fc moiety. Despite not being ingested by the neutrophils, the surface associated anti-CD18- and anti-CD11b-coated particles were able to activate the neutrophil NADPH-oxidase. Also anti-CD11a- (the alpha subunit of LFA-1) and to a lesser extent anti-CD11c- (the alpha subunit of CR4) coated particles were able to trigger the NADPH-oxidase. The NADPH-oxidase was activated without extracellular release of reactive oxygen species. The activity was inhibited by cytochalasin B, suggesting a necessary role for the cytoskeleton in the signalling pathway that activates the oxidase. We show that particle-mediated cross-linking of beta(2)-integrins on the neutrophil surface initiates a signalling cascade, involving cytoskeletal rearrangements, leading to an activation of the NADPH-oxidase without phagosome formation or extracellular release of reactive oxygen species.

Antibodies↗
PubMed2001

New electron backscatter correction factors for accurate skin depth dose calculation from skin contamination by hot particles.

New backscatter correction factors have been calculated using the GEPTS Monte Carlo code system for the case of an isotropic electron point source located at the boundary of a semi-infinite water medium. The backscatter correction factor is defined as the ratio of the dose in a semi-infinite medium to the dose, at the same point, in an infinite medium. It is found that the backscatter correction factor variation with position inside the medium is significant. However, the backscatter correction factor variation with energy is quite small for electron energies less than 1 MeV. The backscatter correction factor data are tabulated for energies of 1, 2, 3, and 4 MeV as functions of radial distance and angular direction. The proposed backscatter correction factors can be used for skin depth-dose calculations from beta particles emitted by either point sources or planar sources. Arbitrary target volumes and beta particle spectra can be considered. The new backscatter correction factors provide an alternative to the current data for accurate skin depth-dose calculations from skin contamination by hot particles.

Beta Particles↗
PubMed1996

Microdosimetry and radiocurability: modelling targeted therapy with beta-emitters.

Tumour control probability (TCP) is a more relevant quantity than the dose distribution in the target volume for estimating the likely efficacy of any type of radiation therapy, be it external beam or targeted using radionuclides. This paper concentrates on a TCP modelling study, for tumour spheres of different radii assuming a uniform uptake of six different beta emitters (ranging from 67Cu to 90Y or 0.58 to 2.3 MeV in endpoint energy). The dose at varying radii, expressed as a fraction of the equilibrium dose, D beta (R)/Deq, was computed by numerical integration of the point-dose kernel over the sphere volume, and shows clearly the effect of electron disequilibrium for small radii and also at the edges of the spheres. These D beta(R)/Deq were converted into volume-dose distribution V(D) and thence into clonogenic cell numbers, n(D), from which the TCPs for spheres of different radii were computed, for different cumulated activities per unit mass, in megabecquerel hours per gram assuming a clonogenic cell density of 10(8) cm-3 and a tumour-cell radiosensitivity alpha of 1.0 Gy-1. Using V(D) rather than simply the mean dose decreases the TCP at both large and small tumour radii for a given number of megabecquerel hour per gram. Curves of iso-TCP go through a shallow minimum in megabecquerel hour per gram at a tumour radius approximately equal to the maximum beta-particle range. The fall in dose at small radii outweighs the reduction in cell number, making it improbable that micrometastases can be eliminated solely by beta-emitters targeted to the tumour cells. An explicit comparison with external-beam therapy for a fixed number of tumour cells divided into different numbers of spheres further emphasizes the difficulties caused by small tumours in beta-particle targeted therapy. Alternative strategies to overcome these limitations are briefly discussed.

Beta Particles↗
PubMed2006

Electrooptics of beta-FeOOH particle in aqueous media 2. Field-strength dependence of decay and steady-state birefringence, and the hydrodynamic and electrooptic properties.

Steady-state and decay birefringence, expressed in terms of the optical phase retardation per cell length delta/d, was measured on beta-FeOOH in aqueous ionic media at 633 nm and at 25 degrees C by an electric square-pulse technique over a wide range of field strength E to ca. 6 kV/cm. The field-strength dependence of both delta/d and field-free rotational relaxation time tau was determined at the sample concentrations between 0.0011 and 0.055 g/L and in the 0.02-2.0 mM NaCl concentration range. Extrapolation of both delta/d and tau values to infinitely high fields (E(2)-->infinity) could yield birefringence- and weight-average quantities, respectively. Observed tau values were decreased at weak fields but leveled off to ca. 0.3 ms at very high fields due to a slight polydispersity regarding the length and volume of particles. The weight-average relaxation time tau(w) was calculated with Perrin's expressions theoretically from the length, width, and volume of beta-FeOOH particles estimated in the dried state from electron micrograph. These quantities were variously averaged. The size distribution was discussed in terms of observed discrete histogram and theoretical (Weibull and Lansing-Kraemer) distribution functions. The sign of observed delta/d value was always positive. The infinitely high-field (delta/d)(infinity) values and the reduced optical anisotropy factor Delta g/n were evaluated by fitting to theoretical orientation functions. The intrinsic birefringence (n3-n1) could be estimated with the mean refractive index n(p) reported in the literature. For the spindle-shaped particle with an axial ratio of ca. 4, the sign of Delta g/n is always positive, whereas the quantity (n3-n1) was either negative (n(p) > 2.35) or positive (n(p) < 2.05) in sign or nearly zero (ca. n(p) = 2.26), depending critically on the n(p) values.

Journal Article↗
PubMed1987

A quantitative method for the detection and localization of quantum-limited events from radionuclides in cells and tissue sections by computer-enhanced video microscopy.

Cellular dynamics often involve extremely low concentrations of biologically active substances, which can be radiolabeled and detected, localized and quantitated by autoradiography. The latter may require exposures from a few days to many months. The objective of this research was to demonstrate the feasibility of reducing this long period of data collection by one to two orders of magnitude, while maintaining or improving the spatial resolution and localization in tissues and the quantitative characteristics inherent in autoradiography. A mathematical model describing the complete system was generated using energy partition calculations to estimate photon production via scintillant per H3 beta particle emission and to estimate the subsequent photon capture based upon imaging system parameters and microscope geometry. Calculations showed that, typically, a single tritium beta particle produces a maximum of 5.8 X 10(3) photons. A photon-limited camera and microscope imaging system were selected and optimized in conjunction with a specially developed physical scintillation model. Results showed that the number of detected photoevents increases monotonically with both signal integration time and, independently, with the concentration of the radionuclide. Consequently, this work demonstrates that video microscopy imaging methods can spatially and temporally quantify very low concentrations of radiolabeled substances and can reduce data acquisition times.

Beta Particles↗
PubMed2002

Experimental validation of Monte Carlo depth-dose calculations using radiochromic dye film dosimetry for a beta-gamma 153Sm radionuclide applied to the treatment of rheumatoid arthritis.

In this work we compare the Monte Carlo (MCNP4B) calculated beta-gamma depth-dose profile for a liquid 153Sm beta-gamma source used in radiation synovectomy with the experimental depth-dose distribution obtained using radiochromic dye film dosimetry. The calculated and experimental depth-dose distribution shows a very good agreement (within 5%) in the region where the dose deposition is dominated by the beta particle component (first 800 microm depth on tissue-equivalent material). The agreement worsens, reaching a maximum deviation of 15%, at depths close to the maximum range of the beta particles. Finally the agreement improves for the region where the gamma component accounts for one-third of the total absorbed dose (depths >1 mm). The possible contributions to these differences are discussed, as well as their relevance for the application of 153Sm in the treatment of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2000

Principles of radioimmunotherapy for hematologists and oncologists.

Recent trials with radiolabeled monoclonal antibodies targeting lymphoid surface membrane antigens have shown high response rates and tolerable toxicity. Radiolabeled antibodies emit continuous, exponentially decreasing, low-dose-rate radiation, whereas conventional external-beam radiotherapy delivers intermittent, fractionated radiation at higher dose rates. The most common isotopes used for radioimmunotherapy (iodine 131 and yttrium 90) kill cells primarily by emission of beta particles (electrons), which are believed to induce DNA strand breaks. The beta particles of Y 90 are more energetic than those of I 131, and affect cells over a radius of 5 mm compared with 0.9 mm to 1.0 mm for I 131. In addition, I 131 emits long-range gamma rays that permit direct imaging with a gamma camera, but also deliver a whole-body radiation dose and may pose a risk to health care workers. Physical barriers to effective delivery of radioimmunotherapy include the heterogeneous tumor vasculature, slow diffusion and convection rates of large antibody molecules through the interstitial fluid, heterogeneous biodistribution of antibodies in tumor nodules, and high intratumoral pressures impeding antibody influx into tumors. Despite these obstacles, multiple trials have shown the efficacy of radioimmunotherapy, particularly for B-cell lymphomas treated with anti-CD20 antibodies, in which response rates of 60% to 90% have been reported.

Antibodies, Monoclonal↗
PubMedDate not supplied

Environmental lead-210 and bismuth-210 accrue selectively in the brain proteins in Alzheimer disease and brain lipids in Parkinson disease.

We studied the occurrence of the environmental radon daughters, 210Po (alpha particles), and 210Bi (beta particles), in the protein and lipid fractions of cortical gray and subcortical white matter from the frontal and temporal lobes of human brains of persons with Alzheimer disease (AD), persons with Parkinson disease (PD), smokers, or persons with no previous evidence of clinical neurologic disease (controls). We found a 10-fold increase in 210Po and 210Pb radioactivity in the protein fraction from both the cortical gray and subcortical white matter in AD and smokers, and a similar increase in the lipid fraction in PD. The pathognomonic distribution of the radon daughters to the lipids in PD and to the proteins in AD was inferred to reflect the increase of local chlorine availability to which radon daughters bound selectively. Cigarette smoking strongly increases radon daughter retention in the central nervous system.

Aged↗
PubMed1978

Glycogen changes in the liver cells of young rats following isoprenaline treatment. (Histochemical and ultrastructural investigations).

Glycogen changes were investigated by light and electron microscopy in the liver cells of newborn rats following isoprenaline (IPR) treatment either for 1 day (2 intraperitoneal injections at 12 h interval), or for 8 days (2 intraperitoneal injections daily). On the day following the interruption of both treatments glycogen depletion was observed as compared to control rats, as evaluated by PAS reaction and confirmed by higher total phosphorylase activity. During this stage electron microscopy revealed mainly alpha-particles of glycogen associated to highly dilated smooth endoplasmic reticulum (SER) after 1-day-treatment, and to mostly increased SER after prolonged treatment. In the animals submitted to prolonged IPR administration and sacrificed at later times, glycogen masses intensely PAS-positive were strongly increased, while the activity of total phosphorylase proved accordingly lower than in the rats sacrificed at earlier times. Electron microscopy examination confirmed an increased amount of glycogen (alpha- and beta-particles) differently distributed: beta-particles were more numerous in the liver of the rats sacrificed on the last day of the experiment. At this time SER didn't appear modified as compared to control rats.

Animals↗
PubMed2006

The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

Beta Particles↗
PubMed1987

No disturbance of myelination in the central nervous system by selective 3H beta-irradiation.

The effect of a selective irradiation of myelin by 3H beta-particles was studied by light and electron microscopic methods in guinea pig spinal cord. The animals were injected with [3H]leucine shortly after birth when the rate of myelin biosynthesis is high and sacrificed 130 days later. In spinal cord the radioactivity was mainly preserved in myelin because the half life of myelin proteins is much higher than that of most other CNS proteins. As a consequence the irradiation dose in the white matter was much higher than in the gray matter. In myelin internally irradiated by 3H beta-particles within 130 days at a dose of 10 Gy no alterations could be detected either by morphological or by morphometric methods.

Animals↗
PubMed2000

The 90-day coronary vascular response to (90)Y-beta particle-emitting stents in the canine model.

PURPOSE: Long-term preclinical studies using continuous, low-dose-rate vascular brachytherapy with (32)P beta-emitting stents have yielded largely disappointing results. In contrast, a shorter half-life, higher dose-rate (90)Y beta-emitting stent more closely mimics the delivery dose rate characteristics of clinically effective beta- and gamma-wire and balloon brachytherapy devices. We evaluated the dose response characteristics of a (90)Y beta-emitting stent in the canine coronary injury model and hypothesized that this device would reduce neointimal formation. METHODS: Seventy-seven (90)Y beta-emitting coronary stents (15 mm BXTM, 3.0- and 3.5-mm diameter) were implanted in 26 normal dogs (20-25 kg) using a randomized, blinded study design. Stent activity included nonradioactive controls (n = 24), 4.5 microCi (n = 15), 8 microCi (n = 12), 16 microCi (n = 18), and 32 microCi (n = 8). Histologic endpoints were assessed at 3 months. RESULTS: Luminal stenosis and neointimal area were similar in control stents and low-activity (4.5 and 8 microCi) (90)Y stents. Higher activity stents (16 and 32 microCi) were associated with significant adverse effects. Frequent total occlusions (5 of 18 stents, 28%; p = 0.008) and a 40% increase in neointimal area (p = 0.024 vs. control) occurred in the 16 microCi group. Incomplete neointimal healing and a trend for reduced neointimal cell density were evident only in the 16- and 32-microCi group. CONCLUSION: Despite unique characteristics (2.7 day half-life and a higher dose rate) of (90)Y beta-emitting coronary stents, they have an adverse effect on neointimal formation, including frequent total occlusions at high activity levels. Incomplete healing, present 90 days (33 half-lives) after stent placement, indicates prolonged recovery from radiation injury.

Animals↗
PubMed2001

Effect of beta radiation on the crystallization of sodium chlorate from water: a new type of asymmetric synthesis.

Sodium chlorate is an achiral molecule that crystallizes from water in the chiral space group P2(1)3. In the absence of chiral perturbations, a random distribution of (+) and (-) crystals is obtained. Kondepudi(2) has shown that constantly stirring an evaporating NaClO(3) solution gives mostly either (+) or (-) crystals. Repeating this experiment many times gives equal numbers of (+) and (-) sets of crystals. Herein we report that when evaporating aqueous NaClO(3) is subjected to beta particles from an Sr-90 source, an asymmetric distribution of (+) and (-) crystals favoring the (+) crystals is obtained. The beta particles are energetic polarized electrons that are approximately 80% of left-handed helicity. By a poorly understood mechanism, the spin polarized electrons produce chiral nucleating sites that favor formation of the (+)-NaClO(3) crystals. Exposure of the evaporating solution instead to energetic positrons from an Na-22 source yields mainly (-)-NaClO(3) crystals. Polarized positrons are of predominantly right-handed helicity. One may conclude that the chirality of the radiation is correlated with the chirality of the crystals being generated.

Journal Article↗
PubMed1998

Radioprotection against lethal damage caused by chronic irradiation with radionuclides in vitro.

To examine the capacity of chemical protectors to mitigate damage caused by chronic irradiation by incorporated radionuclides in vitro, cells must be maintained in the presence of the protector during the course of the irradiation. Such long exposures to chemical protectors at concentrations high enough to afford protection usually results in extreme chemotoxicity. To overcome this problem, experimental conditions were developed to allow Chinese hamster V79 cells to be maintained in 5% DMSO for prolonged periods (up to 72 h) with no observable chemotoxicity. Under these conditions, the capacity of DMSO to protect against damage to V79 cells caused by unbound 32P and 3H2O and DNA-incorporated (131)IdU, [3H]dThd and 125IdU was examined. The dose modification factors for 32P, 3H2O, (131)IdU, [3H]dThd and 125IdU were 2.6+/-0.5, 2.3+/-0.3, 1.0+/-0.1, 1.16+/-0.07 and 1.07+/-0.02, respectively. These results show that 5% DMSO is capable of protecting cultured V79 cells against lethal damage caused by beta particles emitted by unbound 32P and 3H2O, whereas little or no protection is afforded against damage caused by beta particles emitted by DNA-incorporated (131)I and 3H or low-energy Auger electrons emitted by DNA-incorporated 125I.

Animals↗