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PubMed1998

Thorotrast distribution in monkey bone marrow at early and late times after injection.

Thorotrast, a 25% colloidal suspension of 232ThO2, was formerly used as a radiographic contrast medium. Although epidemiological studies have shown that alpha particles emitted from 232Th and its decay products incorporated in the bone marrow cause leukemia, the use of these data for alpha particle induced leukemogenesis risk estimation has been criticized mainly for inhomogeneity of Thorotrast distribution. Four monkeys were injected with Thorotrast to investigate the degree of inhomogeneity in the thorium content of different bone marrow sites and the cellular localization of Thorotrast. Two were injected via an artery and two via a vein and sacrificed either at 1 wk or 3 to 4 y after injection. Microscopic, solid state autoradiography and back scatter electron imaging methods were applied to several bone sites to determine the degree of inhomogeneity. Quantification was performed using x-ray fluorescence for trabecular bone and bone marrow and neutron activation analysis for compact bones. At 1 wk Thorotrast was found to be distributed evenly in the red marrow; by 3 and 4 y conglomerates were seen which were restricted to macrophages. The monkey was found to be a good model for humans. The choice of injection route did not noticeably affect the Thorotrast distribution in bones of the skeletal system. Considering the even distribution of Thorotrast within the red bone marrow at early times after its injection, the inevitable diffusion of thorium progeny from the particles, the mobility of bone marrow macrophages, and the well established correction factor of self-absorption within conglomerates, these results suggest that data derived from Thorotrast patients are useful for risk estimation of alpha particle induced leukemia.

Animals↗

PubMed1989

An alternative method for Ra determinations in water.

Concentrations of 226Ra and 224Ra in 13 wells distributed throughout McCulloch and Mason counties in the Hickory Aquifer of the Llano Uplift Region of West-Central Texas are reported. Measurable alpha-particle activity is present in all wells, with seven wells having 226Ra radioactivity concentrations greater than 185 Bq m-3 (5 pCi L-1). An alternative methodology for measuring 226Ra, 224Ra and 228Ra is described. The EPA-approved methodology for estimating total Ra is shown to be invalid for aquifers containing significant levels of 224Ra. Alpha-particle activity measurements made in the interval of 12 to 300 h after Ra isolation lead to self-consistent solutions for radioactivity concentrations of 226Ra and 224Ra, with negligible contributions from 228Ra. Radioactivity concentrations of 228Ra can be calculated from grow-in terms for this isotope used with alpha-particle activity measurements at post-isolation times significantly longer than 800 h. Comparison of the 226Ra radioactivity concentration with that reported previously by the Texas Department of Health for a single well indicates acceptable agreement. However, the radioactivity concentration attributable to 228Ra for the same well was found to be in significant disagreement with the Texas Department of Health value.

Alpha Particles↗

PubMed1994

Analysis of survival of C-18 cells after irradiation in suspension with chelated and ionic bismuth-212 using microdosimetry.

A previous analysis of non-stochastic dose (Jostes et al., Radiat. Res. 127, 211-219, 1991; Schwartz et al., Health Phys. 62, 458-461, 1992) based on data obtained during irradiations of C-18 cells in suspension by alpha particles emitted from two forms (chelated and ionic) of 212Bi was made using survival curves. No appreciable difference in slope (1/D0) was found between the two forms. Such non-stochastic analyses do not account for the large differences in specific energies deposited in the individual cell nuclei. This microdosimetric (stochastic) analysis aims to determine the survival sensitivity (1/z0) of the individual C-18 cells using the distribution of specific energies deposited in the individual cell nuclei. The resulting sensitivity is greater for the alpha particles emitted from the chelated 212Bi than from the ionic 212Bi. An attempt to account for this greater sensitivity in terms of greater LET of alpha particles passing through the cell nuclei from the chelated 212Bi is unsuccessful. Instead the greater sensitivity disappears if the microdosimetric analysis uses average values for the radii of the cell and of its nucleus rather than the values (from the peak in the cell size distribution) used by the non-stochastic dose analysis.

Alpha Particles↗

PubMed1993

Leukemia and other related hematological disorders among Danish patients exposed to Thorotrast.

At least 60 case studies of leukemia among people exposed to chronic low-dose alpha-particle radiation from injections with the radiographic contrast medium Thorotrast and 115 cases from follow-up studies have been described in the literature. In the present study, malignant hematological diseases among 1003 Danish patients injected during 1935-1947 and followed to 1992 accruing 20,433 person-years were assessed and available histopathological specimens revised. The mean cumulative bone marrow alpha-particle radiation dose (1.34 Gy) was estimated from records of the amount of Thorotrast injected (mean 18.7 ml). Sixteen cases of acute myelogenous leukemia (AML) and seven cases of myelodysplastic syndrome (MDS) were diagnosed 8-40 years after injection, the cumulative frequency reaching 7.6%. No significant relationship was seen between the cumulative frequency of AML + MDS and the age at injection, gender, or amount of Thorotrast injected, but a multivariate analysis described data best by a model with the bone marrow dose and the power of the attained age. The risk estimate for AML + MDS was 173 cases/10(4) persons per Gy. If also considering cases of acute lymphocytic leukemia (1), chronic myelogenous leukemia (3), non-Hodgkins lymphoma (4), and multiple myeloma (2), the risk estimate became 248 cases/10(4) persons per Gy. It is suggested that RBE of alpha particles from thorium may be lower than 20.

Adolescent↗

PubMed1994

Hits to bone cell nuclei from nonuniform radioactive labels.

The stochastic aspects of alpha-particle traversals through nuclei of bone-lining cells from nonuniform radioactive labels are worked out. Both the residence time of the target and the hit rate are considered random variables. It is shown that with any type of bone remodeling the fraction of cells not hit increases with increasing nonuniformity of the label concentration. Thus, a completely uniform concentration represents the most dangerous situation. A possible negative correlation between residence times and hit rates, observed in some experiments, tends to decrease the probability of alpha-particle hits. As a practical application, the theory is applied to the International Commission on Radiological Protection model of the distribution of 239Pu in the human body. In the case of 50 years of chronic ingestion of 1 annual limit of intake (ALI) per year for class W and chronic inhalation of 1 ALI/year for class Y compounds, more than 19.4 and 8.5% of the nuclei of bone-lining cells are traversed by at least one alpha-particle, respectively.

Alpha Particles↗

PubMed2003

Expression of CONNEXIN43 is highly sensitive to ionizing radiation and other environmental stresses.

To gain a greater understanding of the mechanisms underlying the cellular responses to low-dose ionizing radiation, gene expression profiles were examined by microarray analysis of cDNA from confluent human diploid fibroblast cultures exposed to very low fluences of alpha-particles. The data, supported by Northern and Western analyses, indicate that radiation induces a significant up-regulation of CONNEXIN43 expression. This phenomenon was observed in a variety of irradiated cell types. These findings are consistent with our previous observations that connexin43 (cx43)-mediated gap-junction intercellular communication is involved in the bystander response observed in cell cultures exposed to fluences of alpha-particles by which only a very small fraction of the cell nuclei is traversed by a particle track (E. I. Azzam et al., Proc. Natl. Acad. Sci. USA, 98: 473-478, 2001). Increased mRNA levels in cells from irradiated cultures correlated with increased cx43 protein levels by approximately 4 h after irradiation. The induction of cx43 was observed by mean alpha-particle doses as low as 0.16 cGy, and also in cells exposed to gamma-rays, t-butyl hydroperoxide, and hyperthermia. Exposure to these stresses also resulted in post-translational modification of cx43; increased phosphorylation and hyperphosphorylation of the protein was observed. Up-regulation of cx43 expression in ionizing radiation exposed cells correlated with functional communication through gap junctions, as evidenced by dye transfer from irradiated to nonirradiated cells. In contrast, the response after UV radiation varied and was cell type-dependent. Overall, these data suggest a critical role for genes involved in intercellular communication in mediating the cellular responses to a variety of stresses.

Alpha Particles↗

PubMed2001

Computational approach for determining the spectrum of DNA damage induced by ionizing radiation.

To study the characteristics of molecular damage induced by ionizing radiation at the DNA level, Monte Carlo track simulation of energetic electrons and ions in liquid water, a canonical model of B-DNA, and a comprehensive classification of DNA damage in terms of the origin and complexity of damage were used to calculate the frequencies of simple and complex strand breaks. A threshold energy of 17.5 eV was used to model the damage by direct energy deposition, and a probability of 0.13 was applied to model the induction of a single-strand break produced in DNA by OH radical reactions. For preliminary estimates, base damage was assumed to be induced by the same direct energy threshold deposition or by the reaction of an OH radical with the base, with a probability of 0.8. Computational data are given on the complexity of damage, including base damage by electrons with energies of 100-4500 eV and ions with energies of 0.3-4.0 MeV/nucleon (59-9 keV microm(-1) protons and 170-55 keV microm(-1) alpha particles). Computational data are presented on the frequencies of single- and double-strand breaks induced as a function of the LET of the particles, and on the relative frequencies of complex single- and double-strand breaks for electrons. The modeling and calculations of strand breaks show that: (1) The yield of strand breaks per unit absorbed dose is nearly constant over a wide range of LET. (2) The majority of DNA damage is of a simple type, but the majority of the simple single-strand breaks are accompanied by at least one base damage. (3) For low-energy electrons, nearly 20-30% of the double-strand breaks are of a complex type by virtue of additional breaks. The proportion of this locally clustered damage increases with LET, reaching about 70% for the highest-LET alpha particles modeled, with the complexity of damage increasing further, to about 90%, when base damage is considered. (4) The extent of damage in the local hit region of the DNA duplex is mostly limited to a length of a few base pairs. (5) The frequency of base damage when no strand breaks are present in the hit segment of DNA varies between 20-40% as a function of LET for protons and alpha particles.

Alpha Particles↗

PubMed2004

Effect of medium on chromatin damage in bystander mammalian cells.

In the present study, we examined the potential contribution of irradiated medium to the bystander effect using custom-made double-Mylar stainless steel rings. Exponentially growing human-hamster hybrid (A(L)) cells were plated on either one or both sides of double-Mylar dishes 2-4 days before irradiation. One side (with or without cells) was irradiated with alpha particles using the track segment mode of a 4 MeV Van de Graaff accelerator at the Radiological Research Accelerator Facility of Columbia University. Since alpha particles can traverse only a very limited distance (around 23 microm in water), cells plated on the other side of a medium-filled Mylar dish will not be irradiated by the alpha particles. The results of the cytogenetic assay of unirradiated target cells that were attached to the top Mylar layer indicate that the number of chromatid-type aberrations was higher when there was a bottom layer of cells in the medium-filled chambers than with just medium alone. Furthermore, when the medium was transferred from these cell-irradiated dishes to fresh A(L) cell cultures, chromatid-type aberrations were produced in the unirradiated fresh cells. In contrast, medium irradiated in the absence of cells had no effect on chromatid aberrations. These results suggest that certain unidentified modulating factors secreted from the irradiated cells on the bottom Mylar layer into the medium induce chromatin damage in the unirradiated bystander cells.

Animals↗

PubMed1987

In vitro killing of melanoma by liposome-delivered intracellular irradiation.

To better understand and optimize the mechanism of alpha particle killing of tumors, an in vitro model utilizing liposomes as carrier vehicles was developed to study the killing of melanoma via intracellular alpha-irradiation. The radionuclide 212Pb (lead), with its 10.6-hour half-life and alpha-emitting daughter 212Bi (bismuth), was encapsulated in liposomes to achieve the intracellular irradiation of melanoma cells in culture. In dose-response experiments, B16F10 mouse melanoma cells were incubated with liposomes 212Pb/212Bi bound to dextran 70. Plating efficiency and growth of the melanoma cells cultured on gridded petri dishes after incubation were compared with controls at 24 and 48 hours. Greater than 85% cell killing occurred by 48 hours, with administered radioactivity levels of 1.6 dpm/mumol of lipid/cell, which corresponds to intracellular delivery of five to seven alpha particles per cell. These alpha doses can be exceeded in vivo with recirculation or in a perfusion circuit, and more efficient cytotoxic action may be possible.

Alpha Particles↗

PubMed1997

The signal recognition particle receptor alpha subunit of the hyperthermophilic archaeon Acidianus ambivalens exhibits an intrinsic GTP-hydrolyzing activity.

Two adjacent genes of the acidophilic and hyperthermophilic crenarchaeon Acidianus ambivalens were cloned and sequenced. The 1.6 kb genomic nucleotide sequence under investigation consists of the 1.12 kb SRa gene encoding the putative signal recognition particle receptor alpha subunit (SR alpha, 42.2 kDa) and the 186 basepair secE gene coding for the putative secretory component secE subunit (6800 Da). The SR alpha protein is structured by three distinct regions: the N-terminal hydrophilic H-region, the following X-region and the C-terminal GTP-binding domain. A polyclonal anti-E. coli lacZ/A. ambivalens SR alpha antiserum detects a 51 kDa cell protein (p51) on immunoblots. Proteolysis of the recombinant SR alpha protein by Proteinase K produces a 31.6 kDa protease-resistant protein fragment comprising X-region and G-domain. The protein binds tightly to the GTP-agarose affinity matrix in a temperature-dependent manner. It hydrolyzes GTP readily at higher temperatures only in the presence of Mg2+. Point mutations (T326N) and (D329A) in the G-4 element of A. ambivalens SR alpha G-domain diminish the GTPase activity significantly. In contrast, the deletion mutant protein SR alpha (delta1-92) lacking the hydrophilic H-region displays a higher GTP-hydrolyzing activity when compared to the unmodified recombinant protein. Addition of GDP greatly inhibits GTP hydrolysis in mutant and unmodified A. ambivalens SR alpha.

Amino Acid Sequence↗

PubMed1997

DNA damage-inducible genes as biomarkers for exposures to environmental agents.

A biodosimetric approach to determine alpha-particle dose to the respiratory tract epithelium from known exposures to radon has been developed in the rat. Cytotoxicity assays have been used to obtain dose-conversion factors for cumulative exposures typical of those encountered by underground uranium miners. However, this approach is not sensitive enough to derive dose-conversion factors for indoor radon exposures. The expression of DNA damage-inducible genes is being investigated as a biomarker of exposure to radon progeny. Exposure of cultures of A549 cells to alpha particles resulted in an increase in the protein levels of the DNA damage-inducible genes, p53, Cip1, and Gadd45. These protein changes were associated with a transient arrest of cells passing through the cell cycle. This arrest was typified by an increase in the number of cells in the G1 and G2 phases and a decrease in the number of cells in the S phase. The effect of inhaled alpha particles (radon progeny) in rats was examined in the epithelial cells of the lateral well of the anterior nasal cavity. Exposures to radon progeny resulted in a significant increase in the number of cells in the G1 phase and a decrease in the number of cells in the S phase. These cell-cycle changes were concomitant with an increase in the number of cells containing DNA strand breaks. These results suggest a commonality between cell-cycle events in vitro and in vivo following exposure to ionizing radiation. In addition to ionizing radiation, A549 cells were exposed to 4-nitroquinoline-1-oxide, methyl methanesulphonate, crocidolite asbestos, and glass microfiber. These studies showed that physical and chemical agents induce different expression patterns of p53, Cip1, and Gadd153 proteins and they could be used to discriminate between toxic and nontoxic materials such as asbestos and glass microfiber. The measurement of gene expression in A549 cells may provide a means to identify a broad spectrum of physical and chemical toxicants encountered in the environment.

4-Nitroquinoline-1-oxide↗

PubMed1995

An amino-terminal domain containing hydrophobic and hydrophilic sequences binds the signal recognition particle receptor alpha subunit to the beta subunit on the endoplasmic reticulum membrane.

The signal recognition particle receptor consists of two subunits of 72 kDa (SR alpha) and 30 kDa (SR beta). Assembly of SR alpha on the endoplasmic reticulum membrane can occur independent of the signal recognition particle-mediated translocation pathway. To identify the sequences within SR alpha necessary for membrane binding, a series of amino-terminal and internal deletion mutants was constructed and translated in a cell-free system. In addition, nascent SR alpha polypeptides of varying lengths were generated by cycloheximide treatment of translation reactions. Microsome binding assays performed on these polypeptides revealed a membrane binding domain consisting of the amino-terminal 140 residues of SR alpha. This domain includes the two hydrophobic sequences originally proposed to bind to membranes and a highly charged region not previously implicated in membrane assembly. Furthermore, the domain forms a protease-resistant folding unit that after proteolysis can target and anchor onto microsomes. Extraction of microsomal SR alpha at high pH supplemented with 1 M NaSCN suggests that SR alpha and the membrane binding domain are not integrated in the endoplasmic reticulum membrane. The membrane binding domain is also the major site of tight binding with SR beta, suggesting that SR beta plays a role in the membrane assembly of SR alpha.

Amino Acid Sequence↗

PubMed1991

Radon dosimetry based on the depth distribution of nuclei in human and rat lungs.

Calculation of the absorbed dose by different lung cells is necessary for predicting the critical cells that are subject to injury from inhaled Rn and other alpha-particle sources. The absorbed dose was determined for cells in the airways of human and rat lungs, based on airway epithelial thickness and on cell cytoplasm and nuclear volume density as a function of depth from the luminal surface of the airway epithelium. The thickness of the stratified columnar epithelium of human airways varied from 57.8 micron in bronchi to 9.8 microns in bronchioles. The cell populations of all bronchi in human lungs were comparable. The cell populations of trachea and intrapulmonary airways in rats, however, were significantly different. Basal cell populations in rat trachea and human bronchi were similar and formed a nearly continuous layer. In rat bronchi, basal cells were not present in significant numbers. Measurements of epithelial thickness and volume density were used to estimate the absorbed dose for an alpha-particle source (214Po or 218Po) distributed uniformly in the mucus with an equivalent activity of 1 dpm per cm2 of epithelial surface. The following model predictions of dose to human bronchial epithelial cell nuclei for a 218Po alpha-particle source are provided in units of nanogray (nGy) for specific cell types: secretory 158, preciliated 114, ciliated 44, goblet 86, basal 78, and indeterminate cell nuclei 73. The absorbed dose to specific types of rat bronchial epithelial cell nuclei was also predicted: secretory 237, precillated 216, ciliated 203, goblet 204, basal 200, and indeterminate cell nuclei 166 nGy. These and other results indicate that human and rat airway dosimetry have significant differences that may contribute to the differences in cancer cell induction between the two species.

Alpha Particles↗

PubMed2005

Immunochemical analysis of protein expression in breast epithelial cells transformed by estrogens and high linear energy transfer (LET) radiation.

Breast cancer is a complex disease involving numerous genetic aberrations. Immunochemical analysis of protein expression is presented in a human breast epithelial cell line neoplastically transformed by high linear energy transfer (LET) alpha particle radiation in the presence of 17beta estradiol (E) and in the parental human breast epithelial cell line (MCF-10F) which served as a non-tumorigenic control. The aim of this work was to determine the levels of mRNA and protein expression in control and transformed cells at various stages of the neoplastic process. The levels of mRNA and protein expression of PCNA, c-fos, JNK2 and Fra-1 were increased in the transformed cell line compared to the levels in non-tumorigenic control cells. The transforming factor Rho A was significantly increased only in the tumor cell line. Furthermore, the levels of mRNA and protein expression of ErbB2 were significantly increased in the transformed cell line and in tumor cells derived from the transformed cells after injecting them into nude mice. A decrease in RbA/p48 protein expression and mRNA levels was observed in cells treated with double doses of alpha particle radiation in the presence of estrogen, regardless of tumorigenicity. Such expression was lower than that in the control untreated MCF-10F cells. In summary, these studies show that estrogen and high LET-radiation induce changes in oncoprotein expression and mRNA levels of human breast cell lines. These changes are indicative of a cascade of events that characterize the process of cell transformation in breast cancer. These results provide evidence that multiple steps with consecutive changes are involved when normal cells become tumorigenic cells as a result of alpha particle irradiation and estrogen treatments.

Adult↗

PubMed2004

Tissue distribution of Thorotrast and role of internal irradiation in carcinogenesis.

Carcinogenesis in Thorotrastosis has been assumed due to direct bombardment by alpha-particle with high linear energy transfer during decay of 232Th. To revisit the mechanism of carcinogenesis by Thorotrast (THR), we examined the tissue distribution of THR granules and two-dimensional distribution of radioactivity in the organs of Thorotrastosis patients and studied their spatial relationship to histopathological changes. The high radioactivity in the patients' organ was predominantly derived from decay of Thorium series and showed unique distribution, while the far lower natural radioactivity was mainly from Uranium series decay and fairly evenly distributed. It was found that a large majority of THR granules were phagocytized by macrophages and were embedded in extensive fibrosis. Cancer was rarely in the center of THR deposition but rather at a distance from the deposits. These observations may indicate that the predominant feature of THR deposition is the tissue damage by direct hit of alpha-particles and subsequent fibrosis. The effect of THR resembles action of toxic chemical agents, as several authors have pointed out. We therefore assume that carcinogenesis in Thorotrastosis is a combination of events, such as regeneration of liver tissue after radiation damage, emission of secondary electrons, ionization of the surrounding tissue, and beta- or gamma-ray from daughter nuclei of Thorium (Th). In this context, the role of alpha-particle is important but more intriguing.

Aged↗

PubMed1999

Radiotoxicity of bismuth-213 bound to membranes of monolayer and spheroid cultures of tumor cells.

Monoclonal antibody 13A to murine CD44 was used to bind the alpha-particle emitter 213Bi to cell surfaces of cultured EMT-6 or Line 1 tumor cells. Data on kinetics and saturation of binding, cell shape and nuclear size were used to calculate the absorbed dose to the nuclei. Treatment of monolayer cells with [213Bi]MAb 13A produced a classical exponential survival curve with no apparent shoulder. Microdosimetry analyses indicated that 1.4-1.7 Gy produced a 37% surviving fraction (D0). Multicellular spheroids were shown to bind [213Bi]MAb 13A mainly on the outer cell layer. Relatively small amounts of activity added to the spheroids resulted in relatively large absorbed doses. The result was that 3-6-fold less added radioisotope was necessary to kill similar fractions of cells in spheroids than in monolayer cells. These data are consistent with the interpretation that the alpha particles from a single 213Bi atom bound to one cell can penetrate and kill adjacent cells. Flow cytometry was used to sort cells originating from the periphery or from the interior of spheroids. Cells from the outside of the [213Bi]MAb 13A exposed spheroids had a lower surviving fraction per administered activity than cells from the interior. Cells were killed efficiently in spheroids up to 20-30 cells in diameter. The data support the hypothesis that alpha-particle emitters should be very efficient at killing cells in micrometastases of solid tumors.

Alpha Particles↗

PubMed1996

A putative signal recognition particle receptor alpha subunit (SR alpha) homologue is expressed in the hyperthermophilic crenarchaeon Sulfolobus acidocaldarius.

A 1.64 kb genomic DNA sequence from the hyperthermophilic crenarchaeon Sulfolobus acidocaldarius is composed of two adjacent genes. The first functionally unassigned open reading frame (orf-1) comprises 450 base pairs. The second 1.1 kb large open reading frame encodes the putative signal recognition particle receptor alpha subunit (SR alpha). Both genes are expressed under the heterotrophic growth conditions of the organism. The main transcript of orf-1 appears as a monocistronic RNA in Northern hybridization. With regard to SR alpha the transcription pattern was investigated by reverse transcription polymerase chain reaction and primer extension analysis. A polyclonal antiserum directed against E. coli lacZ'/Sulfolobus SR alpha fusion protein detects a 40.5 kDa protein (p41) in agreement with the 41.4 kDa as deduced from the nucleotide sequence.

Base Sequence↗

PubMed2003

Targeting of osseous sites with alpha-emitting 223Ra: comparison with the beta-emitter 89Sr in mice.

UNLABELLED: The bone-seeking property and the potential exposure of red marrow by the alpha-particle emitter (223)Ra (half-life, 11.43 d) were compared with those of the beta-emitter (89)Sr (half-life, 50.53 d). METHODS: The biodistributions of (223)Ra and (89)Sr were studied in mice. Tissue uptake was determined at 1 h, 6 h, 1 d, 3 d, and 14 d after intravenous administration. Radiation absorbed doses were calculated for soft tissues and for bone. Multicellular-level doses were estimated for bone marrow cavities. RESULTS: Both (89)Sr and (223)Ra selectively concentrated on bone surfaces relative to soft tissues. The measured bone uptake of (223)Ra was slightly higher than that of (89)Sr. At 24 h, the femur uptake of (223)Ra was 40.1% +/- 7.7% of the administered activity per gram of tissue. The uptake in spleen and most other soft tissues was higher for (223)Ra than for (89)Sr. Although predominant clearance of (223)Ra was observed from the soft tissues within the first 24 h, the bone uptake of (223)Ra, which was not significantly different from maximum after only 1 h, was not significantly reduced during the 14 d. Furthermore, little redistribution of (223)Ra daughter products away from bone was found (2% at 6 h and less than 1% at 3 d). Estimates of dose to marrow cavities showed that the (223)Ra alpha-emitter might have a marrow-sparing advantage compared with beta-emitters for targeting osteoid surfaces because the short-range alpha-particles irradiate a significantly lower fraction of the marrow volumes. At the same time, the bone surfaces will receive a therapeutically effective radiation dose. CONCLUSION: The results of this study indicate that (223)Ra is a promising candidate for high-linear-energy transfer alpha-particle irradiation of cancer cells on bone surfaces. (223)Ra can, together with its daughter radionuclides, deliver an intense and highly localized radiation dose to the bone surfaces with substantially less irradiation of healthy bone marrow compared with standard bone-seeking beta-emitters.

Alpha Particles↗