PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Alpha Particles”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources
PubMed1986

Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy.

Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the alpha-particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycarbonic anhydride of diethylenetriaminepentaacetic acid. The physical properties of 212Bi are appropriate for radioimmunotherapy in that it has a short half-life, deposits its high energy over a short distance, and can be obtained in large quantities from a radium generator. Antibody specific activities of 1-40 microCi/microgram (1 Ci = 37 GBq) were achieved. Specificity of the 212Bi-labeled anti-Tac was demonstrated for the IL-2 receptor-positive adult T-cell leukemia line HUT-102B2 by protein synthesis inhibition and clonogenic assays. Activity levels of 0.5 microCi or the equivalent of 12 rad/ml of alpha radiation targeted by anti-Tac eliminated greater than 98% the proliferative capabilities of HUT-102B2 cells with more modest effects on IL-2 receptor-negative cell lines. Specific cytotoxicity was blocked by excess unlabeled anti-Tac but not by human IgG. In addition, an irrelevant control monoclonal antibody of the same isotype labeled with 212Bi was unable to target alpha radiation to cell lines. Therefore, 212Bi-labeled anti-Tac is a potentially effective and specific immunocytotoxic reagent for the elimination of IL-2 receptor-positive cells. These experiments thus provide the scientific basis for use of alpha-particle-emitting radionuclides in immunotherapy.

Antibodies, Monoclonal↗
PubMed1992

Hit rates and radiation doses to nuclei of bone lining cells from alpha-particle-emitting radionuclides.

Factors relating the local concentration of a bone-seeking alpha-particle emitter to the mean hit rate have been determined for nuclei of bone lining cells using a Monte Carlo procedure. Cell nuclei were approximated by oblate spheroids with dimensions and location taken from a previous histomorphometric study. The Monte Carlo simulation is applicable for planar and diffuse labels at plane or cylindrical bone surfaces. Additionally, the mean nuclear dose per hit, the dose mean per hit, the mean track segment length and its second moment, the percentage of stoppers, and the frequency distribution of the dose have been determined. Some basic features of the hit statistics for bone lining cells have been outlined, and the consequences of existing standards of radiation protection with regard to the hit frequency to cell nuclei are discussed.

Alpha Particles↗
PubMed1998

Vascular targeted radioimmunotherapy with 213Bi--an alpha-particle emitter.

To destroy both tumor blood vessels and adjacent tumor cells, an alpha-particle emitter, 213Bi, has been targeted with a monoclonal antibody (MAb) to vessels that feed lung tumors in mice. Animals, bearing approximately 100 EMT-6 carcinomas each of 50-400 cells in size in the lung, that were treated with 120 muCi of 213Bi-MAb 201B were all cured of their disease. Animals treated when tumors were larger (10(3)-10(4) cells) had extended life spans, but a small number of residual tumors eventually killed the animals. Significant extension of life span was also induced with another tumor model-rat tracheal carcinoma growing in the lungs of SCID mice that were then treated with 136 muCi 213Bi-MAb 201B. These studies indicate that attack of both blood vessels and tumor cells simultaneously is an effective mode of cancer treatment.

Alpha Particles↗
PubMed2001

Radiation risk to low fluences of alpha particles may be greater than we thought.

Based principally on the cancer incidence found in survivors of the atomic bombs dropped in Hiroshima and Nagasaki, the International Commission on Radiation Protection (ICRP) and the United States National Council on Radiation Protection and Measurements (NCRP) have recommended that estimates of cancer risk for low dose exposure be extrapolated from higher doses by using a linear, no-threshold model. This recommendation is based on the dogma that the DNA of the nucleus is the main target for radiation-induced genotoxicity and, as fewer cells are directly damaged, the deleterious effects of radiation proportionally decline. In this paper, we used a precision microbeam to target an exact fraction (either 100% or < or =20%) of the cells in a confluent population and irradiated their nuclei with exactly one alpha particle each. We found that the frequencies of induced mutations and chromosomal changes in populations where some known fractions of nuclei were hit are consistent with non-hit cells contributing significantly to the response. In fact, irradiation of 10% of a confluent mammalian cell population with a single alpha particle per cell results in a mutant yield similar to that observed when all of the cells in the population are irradiated. This effect was significantly eliminated in cells pretreated with a 1 mM dose of octanol, which inhibits gap junction-mediated intercellular communication, or in cells carrying a dominant negative connexin 43 vector. The data imply that the relevant target for radiation mutagenesis is larger than an individual cell and suggest a need to reconsider the validity of the linear extrapolation in making risk estimates for low dose, high linear-energy-transfer (LET) radiation exposure.

Alpha Particles↗
PubMed2001

Absorbed fraction and dose conversion coefficients of alpha particles for radon dosimetry.

The sensitivity to different relevant parameters of the absorbed fraction of alpha particles emitted from the 222Rn chain in sensitive cells of the tracheo-bronchial tree have been investigated. The structure of the airway wall given by ICRP (ICRP66) has been adopted and employed in the present calculations. The source thickness (mucous gel and sol + cilia), target layer thickness and the depth of the sensitive layers have been varied within reasonable ranges around the default values recommended by ICRP66. The results have shown that the depth of the sensitive layers is the most important parameter in calculating the absorbed fraction. In addition, dose conversion coefficients were calculated and presented along with the absorbed fractions.

Alpha Particles↗
PubMed1983

Soft tissue dosimetry of radium in humans--I. Alpha-particle doses from the decay of 226Ra and 228Ra in soft tissues.

Estimates are presented of the alpha particle doses accumulated by individual organs and soft tissues of Reference Man in a 50-yr period following single intakes of 226Ra and 228Ra. With no decay of 226 Ra daughter products in soft tissue, the median dose is 67 mrad per muCi 226Ra intake. With no translocation of 228Ra daughter products, the dose per muCi 228Ra intake is 5.77 times the corresponding value for 226Ra. Biological variability introduces substantial uncertainty when applying these estimates to a particular individual.

Alpha Particles↗
PubMed1994

Cytotoxicity of alpha-particle-emitting m-[211At]astatobenzylguanidine on human neuroblastoma cells.

Radioiodinated m-iodobenzylguanidine (MIBG) has been used with only limited success for the treatment of neural crest tumors including neuroblastoma. Use of an MIBG analogue labeled with 211At could be advantageous because of the shorter range and higher linear energy transfer of its alpha-particle emissions compared with the beta-particles emitted by 131I. The potential utility of m-[211At]astatobenzylguanidine for the treatment of neuroblastoma was investigated in vitro using 3 human neuroblastoma cell lines known to take up MIBG [SK-N-SH, SK-N-BE(2C), and SK-SY5Y] and a control line lacking MIBG uptake (SK-N-MC). Maximum binding of m-[211At]astatobenzylguanidine ([211At] MABG) to 5 x 10(5) cells after a 2-h incubation ranged from 61% for SK-N-SH to 1% for SK-N-MC. Using a limiting dilution clonogenic assay, the cytotoxicity for SK-N-SH cells of [211At]MABG was compared with [211At]astatide and no-carrier-added [131I]MIBG. A D0 of 5.8 nCi/ml was calculated for [211At]MABG compared with 482 nCi/ml for [211At] astatide, indicating a more than 80-fold enhanced cytotoxicity for the specifically targeted alpha-particles of [211At]MABG. For [211At]MABG, the D0 corresponded to only 6.4 211At atoms bound/cell compared with 9000 atoms/cell for no-carrier-added [131I]MIBG. The D0 values measured for [211At]MABG treatment of SK-SY5Y, SK-N-BE(2C), and SK-N-MC cells were 50, 5.8, and 11,043 nCi/ml, respectively, corresponding to 7.04, 6.46, and 171.79 211At atoms bound/cell. In conclusion, these results have demonstrated that [211At]MABG is considerably more cytotoxic than [131I]MIBG and that [211At]MABG could have great potential as a radiotherapeutic agent for the treatment of neuroblastoma.

Antineoplastic Agents↗
PubMed1983

Oncogenic transformation of mouse BALB/3T3 cells by plutonium-238 alpha particles.

The A31-11 mouse BALB/3T3 cell system was adapted for the study of malignant transformation induced by 5.3 MeV alpha particles from a specially constructed 238Pu source. The biologic effects were compared to those of 220 kVp X rays. The alpha-radiation survival curve showed a D0 of 70 rad and a relative biological effectiveness (RBE) of 3.5 at 50% survival. The transformation frequency increased exponentially with dose in the range examined (25-250 rad); the maximum RBE for the induction of transformation in growing cells was approximately 3. The RBE for alpha transformation in nonproliferating cells, however, appeared to be much higher; the yield of transformants among X-irradiated cells held in the stationary phase of growth for 6 to 220 hr after irradiation declined nearly 50-fold while no decrease occurred in alpha-irradiated cells. This finding supports the hypothesis that carcinogenic damage induced by high LET radiation in mammalian cells is inefficiently repaired compared with X-ray damage, and that the carcinogenic effect of exposures to high LET radiation may be simply cumulative in nature. It further suggests that the effective RBE for alpha radiation in nonproliferating cell populations in vivo may be much higher than one would predict based on measurements in dividing cells.

Alpha Particles↗
PubMed1987

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to 60Co gamma-rays, 241Am alpha-particles or bleomycin.

The rejoining of DNA double strand breaks (dsb) induced by 60Co gamma-rays, 241Am alpha-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following alpha-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by gamma-rays or bleomycin.

Alpha Particles↗
PubMed2005

Microdosimetry of radon progeny alpha particles in bronchial airway bifurcations.

A Monte Carlo code, initially developed for the calculation of microdosimetric spectra for alpha particles in cylindrical airways, has been extended to allow the computation of microdosimetric parameters for multiple source-target configurations in bronchial airway bifurcations. The objective of the present study was to investigate the effects of uniform and non-uniform radon progeny surface activity distributions in symmetric and asymmetric bronchial airway bifurcations on absorbed dose, hit frequency, lineal energy, single hit specific energy and LET spectra. In order to assess the effects of multiple hits, dose-dependent specific energy spectra were calculated by solving the compound Poisson process by iterative convolution. While the simulations showed significant differences of cellular dose quantities at different cell locations for uniformly distributed surface activities, even higher variations, as high as several orders of magnitude, were observed for non-uniform surface activity distributions, depending on the location of the cell and the local activity distribution.

Air Pollutants, Radioactive↗
PubMed1989

Local energy deposited for alpha particles emitted from inhaled radon daughters.

An analytical method has been developed to calculate the local energy deposited by alpha particles emitted from radon daughters deposited on the mucus surface in the lung airways. For the particular cases of 218Po (Ra A) and 214Bi (Ra C'), microdose spectra have been evaluated in test spheres of 1 micron diameter which were taken to lie within airways of diameters 18,000, 3,500 and 600 microns. In each case, the contributions of the near and far wall were computed separately. The average microdosimetric parameters yF and yD have also been calculated. For the two smaller airways, yF and yD values were found to be about 110 and 135 keV microns-1 for 218Po and about 87 and 107 keV microns-1 for 214Bi respectively. The corresponding values were about 10% higher for the largest airway.

Alpha Particles↗
PubMed2005

Alpha-particle induced reactions on natSb and 121Sb with particular reference to the production of the medically interesting radionuclide 124I.

Excitation functions of the reactions (nat)Sb(alpha,xn)(123,124,125,126)I and (121)Sb(alpha,xn)(123,124)I were measured from their respective thresholds up to 26 MeV, with particular emphasis on data for the production of the medically important radionuclide (124)I. The conventional stacked-foil technique was used, and the samples for irradiation were prepared by a sedimentation process. The measured excitation curves were compared with the data available in the literature. From the experimental data the theoretical yields of the investigated radionuclides were calculated as a function of the alpha-particle energy. The calculated yield of (124)I from the (nat)Sb(alpha,xn)(124)I process over the energy range E(alpha) = 22-->13 MeV amounts to 1.02 MBq/microA x h and from the (121)Sb(alpha,n)(124)I reaction over the same energy range to 2.11 MBq/microA x h. The radionuclidic impurity levels are discussed. Use of (nat)Sb as target material would not lead to high-purity (124)I. Using highly enriched (121)Sb as target, production of (124)I of high radionuclidic purity is possible; the batch yield, however, is low.

Alpha Particles↗
PubMed1996

Chromosome end-to-end associations and telomerase activity during cancer progression in human cells after treatment with alpha-particles simulating radon progeny.

Chromosome end-to-end associations seen at metaphase involve telomeres and are commonly observed in cells derived from individuals with ataxia telangiectasia and most types of human tumors. The associations may arise because of short telomeres and/or alterations of chromatin structure. There is a growing consensus that telomere length is stabilized by the activity of telomerase in immortal cells; however, it is not clear why some immortal cells display chromosome end-to-end associations. In the present study we evaluated chromosome end-to-end associations, telomere length and telomerase activity with the tumorigenic status of human bronchial epithelial cells immortalized with human papillomavirus. Oncogenic transformation was initiated using radon simulated alpha-particles and cells evaluated as primary, secondary and metastatic transformants. The fewest chromosome end associations and lowest telomerase activity were observed in the parental immortalized cells. However, increased levels of telomerase activity were detected in alpha-particle survivors while robust telomerase activity was seen in the tumorigenic cell lines. The tumorigenic cells that were telomerase positive and had the highest frequency of cells with chromosome end-to-end associations were also metastatic. No correlation was found between telomere length and the different stages of carcinogenicity.

Ataxia Telangiectasia↗
PubMed2005

The promise of targeted {alpha}-particle therapy.

The use of monoclonal antibodies to deliver radioisotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native antibodies. Since the alpha- and beta-particles emitted during the decay of radioisotopes differ in significant ways, proper selection of isotope and antibody combinations is crucial to making radioimmunotherapy a standard therapeutic modality. Because of the short pathlength (50-80 microm) and high linear energy transfer ( approximately 100 keV/microm) of alpha-emitting radioisotopes, targeted alpha-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissues than beta-emitters. These properties make targeted alpha-particle therapy ideal for the elimination of minimal residual or micrometastatic disease. Radioimmunotherapy using alpha-emitters such as (213)Bi, (211)At, and (225)Ac has shown activity in several in vitro and in vivo experimental models. Clinical trials have demonstrated the safety, feasibility, and activity of targeted alpha-particle therapy in the treatment of small-volume and cytoreduced disease. Further advances will require investigation of more potent isotopes, new sources and methods of isotope production, improved chelation techniques, better methods for pharmacokinetic and dosimetric modeling, and new methods of isotope delivery such as pretargeting. Treatment of patients with less-advanced disease and, ultimately, randomized trials comparing targeted alpha-particle therapy with standard approaches will be required to determine the clinical utility of this approach.

Alpha Particles↗
PubMed2006

Simulation of the measured ionisation-cluster distributions of alpha-particles in nanometric volumes of propane.

In the last years, the probability of the formation of ionisation clusters by primary alpha particles at 5.4 MeV in nanometric volumes of propane (20.6 and 24.0 nm in a material of density 1.0 g cm(-3)) was studied experimentally and by Monte Carlo simulation. Calculations were performed taking into account the single electron detection efficiency of the track-nanodosimetric counter, which was estimated on the base of Monte Carlo calculations of electron transport inside the detector. Now a new evaluation of the efficiency has been performed, pointing out a value lower than previously estimated. Besides, the efficiency of the counter in resolving temporally the collected electrons has been calculated, together with its effect on the measured distribution. On the base of these evaluations, a new comparison has been performed between measurements and calculations, pointing out a better agreement than previously reported.

Alpha Particles↗