Internal Emitters Research Articles

Tissue Dose-rate Kernels for Bremsstrahlung Exposure from Internal Electron Emitters.

Radionuclides emitting high-energy beta rays are frequently employed for therapeutic purposes in the field of medicine. However, it is widely recognized that such radionuclides have the potential to generate in vivo bremsstrahlung radiation. This research study focused on investigating the dose rate of bremsstrahlung radiation emanating from a radioactive source embedded in a patient. To accomplish this, we estimate the spectral energy distribution of the generated bremsstrahlung. By employing this spectral distribution, we present a novel method for estimating the bremsstrahlung dose rate kernel applicable to a given combination of source and material. This method considers photon buildup and attenuation, as well as the encapsulation of the radiation source. Furthermore, we provide formulas for both monoenergetic electrons and beta-transition electrons that account for radioactive decay.

Effects of radiation on respiratory disease mortality: analysis of the national registry for radiation workers in United Kingdom

Purpose While some evidence of an effect of radiation exposure on respiratory disease at low dose levels has now emerged, there is heterogeneity in the risks between different studies and countries. In this paper, we aim to show the effect of radiation on three different sub-types of respiratory disease mortality through the analysis of the NRRW cohort in UK. Materials and methods The NRRW cohort consisted of 174,541 radiation workers. Doses to the surface of the body were monitored using individual film badges. Most of the doses are associated with X-rays and gamma rays and to a less extent of beta and neutron particles. The overall mean 10-year lagged lifetime external dose was 23.2 mSv. Some workers were potentially exposed to alpha particles. However, doses from internal emitters were not available for the NRRW cohort. 25% of male workers and 17% of female workers were identified as being monitored for internal exposure. The Poisson regression methods for grouped survival data with a stratified baseline hazard function were used to describe the dependence of the risk on cumulative external radiation dose. The disease was analyzed by the following subgroups: Pneumonia (1066 cases including 17 cases of influenza), COPD and allied disease (1517 cases) and other remaining respiratory diseases (479 cases). Results There was very little radiation effect on pneumonia mortality, but evidence of a reduction in mortality risk for COPD and allied disease (ERR/Sv= −0.56, 95%CI: −0.94, −0.06; p = .02) and an increase in risk for other respiratory disease mortality (ERR/Sv = 2.30, 95%CI: 0.67, 4.62; p = .01) with increasing cumulative external dose were observed. The effects of radiation were more prominent amongst workers monitored for internal exposure. The reduction in mortality risk of COPD and allied disease per cumulative external dose was statistically significant for the radiation workers monitored for internal exposure (ERR/Sv= −0.59, 95%CI: −0.99, −0.05; p = .017) but not significant among the workers who were not monitored (ERR/Sv= −0.43, 95%CI: −1.20, 0.74; p = .42). A statistically significant increased risk was observed for other respiratory diseases among monitored radiation workers (ERR/Sv = 2.46, 95%CI: 0.69, 5.08; p = .019), but not among unmonitored workers (ERR/Sv = 1.70, 95%CI: −0.82, 5.65; p = .25). Conclusion The effects of radiation exposure can be different depending on the type of respiratory disease. No effect was seen in pneumonia; a reduction in mortality risk of COPD, and increased mortality risk of other respiratory diseases were observed with cumulative external radiation dose. More studies are needed to verify these findings.

Stylized versus voxel phantoms: quantification of internal organ chord length distances

Dosimetric calculations, whether for radiation protection or nuclear medicine applications, are greatly influenced by the use of computational models of humans, called anthropomorphic phantoms. As anatomical models of phantoms have evolved and expanded, thus has the need for quantifying differences among each of these representations that yield variations in organ dose coefficients, whether from external radiation sources or internal emitters. This work represents an extension of previous efforts to quantify the differences in organ positioning within the body between a stylized and voxel phantom series. Where prior work focused on the organ depth distribution vis-à-vis the surface of the phantom models, the work described here quantifies the intra-organ and inter-organ distributions through calculation of the mean chord lengths. The revised Oak Ridge National Laboratory stylized phantom series and the University of Florida/National Cancer Institute voxel phantom series including a newborn, 1-, 5-, 10- and 15 year old, and adult phantoms were compared. Organ distances in the stylized phantoms were computed using a ray-tracing technique available through Monte Carlo radiation transport simulations in MCNP6. Organ distances in the voxel phantom were found using phantom matrix manipulation. Quantification of differences in organ chord lengths between the phantom series displayed that the organs of the stylized phantom series are typically situated farther away from one another than within the voxel phantom series. The impact of this work was to characterize the intra-organ and inter-organ distributions to explain the variations in updated internal dose coefficient quantities (i.e. specific absorbed fractions) while providing relevant data defining the spatial and volumetric organ distributions in the phantoms for use in subsequent internal dosimetric computations, with prospective relevance to patient-specific individualized dosimetry, as well as informing machine learning definition of organs using these reference models.

Adaptability of biogas slurry–water ratio and emitter types in biogas slurry drip irrigation system

Biogas slurry drip irrigation (BSDI) can not only save water, but also reduce the use of chemical fertilizers. Determining the appropriate biogas slurry–water ratio (BSWR) and emitter types can ensure long-term stable operation of systems. Therefore, this study proposes an obtaining the BSWR suitable for crop irrigation conductivity method based on conductivity biogas slurry and clean water. The three conductivity levels（1.3, 2.3 and 3.3 mS/cm）are set based on their suitability for crop growth. The corresponding BSWR is determined using the proposed method, i.e.,1:20, 1:8, and 1:4. The clogging dynamic process, clogging location, and characteristic parameters are analyzed using a hydraulic test, an industrial camera and the ordered regression method for three common emitters under three BSWR. The results show that the proposed method relative error is approximately 10%, which is considered feasible. Over time, the discharge and uniformity of emitters decrease, and subsequently remain constant. As the slurry concentration increases, the emitters clog more rapidly, and internal patch emitters (IPEs) show the lowest adaptability to BSDI systems. The pressure compensation (PCEs) and single-wing labyrinth emitters (SWLEs) is better than IPEs on anti-clogging performance. Clogging mainly occurs at the inlet grid, and the SWLEs are clogged at the internal flow channel and outlet. Moreover, the inlet grid and pressure compensation are key characteristic parameters affecting clogging. The adaptability of emitters can be improved by changing the inlet grid layout, increasing the cross-sectional area of the flow channel, and/or reducing the pathway length. Based on irrigation uniformity and economic cost, large discharge SWLEs and PCEs are recommended for one-time field crops and multi-year cash crops respectively. Furthermore, the BSWR should be at least 1:4, and ratios of 1:8–1:20 are most conducive to stable operation. This study serves as a guideline for future development of BSDI systems.

Methods of improving brain dose estimates for internally deposited radionuclides * * This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the US Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or

The US National Council on Radiation Protection and Measurements (NCRP) convened Scientific Committee 6–12 (SC 6–12) to examine methods for improving dose estimates for brain tissue for internally deposited radionuclides, with emphasis on alpha emitters. This Memorandum summarises the main findings of SC 6–12 described in the recently published NCRP Commentary No. 31, ‘Development of Kinetic and Anatomical Models for Brain Dosimetry for Internally Deposited Radionuclides’. The Commentary examines the extent to which dose estimates for the brain could be improved through increased realism in the biokinetic and dosimetric models currently used in radiation protection and epidemiology. A limitation of most of the current element-specific systemic biokinetic models is the absence of brain as an explicitly identified source region with its unique rate(s) of exchange of the element with blood. The brain is usually included in a large source region called Other that contains all tissues not considered major repositories for the element. In effect, all tissues in Other are assigned a common set of exchange rates with blood. A limitation of current dosimetric models for internal emitters is that activity in the brain is treated as a well-mixed pool, although more sophisticated models allowing consideration of different activity concentrations in different regions of the brain have been proposed. Case studies for 18 internal emitters indicate that brain dose estimates using current dosimetric models may change substantially (by a factor of 5 or more), or may change only modestly, by addition of a sub-model of the brain in the biokinetic model, with transfer rates based on results of published biokinetic studies and autopsy data for the element of interest. As a starting place for improving brain dose estimates, development of biokinetic models with explicit sub-models of the brain (when sufficient biokinetic data are available) is underway for radionuclides frequently encountered in radiation epidemiology. A longer-term goal is development of coordinated biokinetic and dosimetric models that address the distribution of major radioelements among radiosensitive brain tissues.

Biofluid Metabolomics and Lipidomics of Mice Exposed to External Very High-Dose Rate Radiation.

High-throughput biodosimetry methods to determine exposure to ionizing radiation (IR) that can also be easily scaled to multiple testing sites in emergency situations are needed in the event of malicious attacks or nuclear accidents that may involve a substantial number of civilians. In the event of an improvised nuclear device (IND), a complex IR exposure will have a very high-dose rate (VHDR) component from an initial blast. We have previously addressed low-dose rate (LDR, ≤1 Gy/day) exposures from internal emitters on biofluid small molecule signatures, but further research on the VHDR component of the initial blast is required. Here, we exposed 8- to 10-week-old male C57BL/6 mice to an acute dose of 3 Gy using a reference dose rate of 0.7 Gy/min or a VHDR of 7 Gy/s, collected urine and serum at 1 and 7 d, then compared the metabolite signatures using either untargeted (urine) or targeted (serum) approaches with liquid chromatography mass spectrometry platforms. A Random Forest classification approach showed strikingly similar changes in urinary signatures at 1 d post-irradiation with VHDR samples grouping closer to control samples at 7 d. Identical metabolite panels (carnitine, trigonelline, xanthurenic acid, N6,N6,N6-trimethyllysine, spermine, and hexosamine-valine-isoleucine-OH) could differentiate IR exposed individuals with high sensitivity and specificity (area under the receiver operating characteristic (AUROC) curves 0.89–1.00) irrespective of dose rate at both days. For serum, the top 25 significant lipids affected by IR exposure showed slightly higher perturbations at 0.7 Gy/min vs. 7 Gy/s; however, identical panels showed excellent sensitivity and specificity at 1 d (three hexosylceramides (16:0), (18:0), (24:0), sphingomyelin [26:1], lysophosphatidylethanolamine [22:1]). Mice could not be differentiated from control samples at 7 d for a 3 Gy exposure based on serum lipid signatures. As with LDR exposures, we found that identical biofluid small molecule signatures can identify IR exposed individuals irrespective of dose rate, which shows promise for more universal applications of metabolomics for biodosimetry.

Extended analysis of solid cancer incidence among the Nuclear Industry Workers in the UK: 1955-2011.

Radiation worker studies provide direct estimates of cancer risk after protracted low-dose exposures to external X-ray and gamma-ray irradiations. The National Registry for Radiation Workers (NRRW) started in 1976 and has become the largest epidemiological program of research on nuclear workers in the UK. Here, we report on the relationship between solid cancer incidence and external radiation at the low-dose levels in 172,452 NRRW cohort members of whom (90%) were men. This study is based on 5.25 million person-years of follow-up from 1955 through the end of 2011. In the range of accumulated low doses two-thirds of workers have doses of less than 10 mSv. This study is an updated analysis of solid cancer incidence data with an additional 10 years of follow-up over the previous analysis of the NRRW cohort (NRRW-3). A total of 18,310 cases of solid cancers based on a 10-year lag were registered and of these 43% of the solid cancer cases occurred during the latest 10 years. Poisson regression was used to investigate the relationship between solid cancers risk and protracted chronic low-dose radiation exposure. This study demonstrated for solid cancers a rapid decrease of risk at high external doses that appeared to be driven by the workers who were monitored for potential exposure to internal emitters and who had also received relatively high external doses. Among cohort members only exposed to external radiation, a strong association was found between external dose and solid cancers (ERR/Sv = 0.52, 95% CI: 0.11; 0.96, based on 13,199 cases). A similar pattern is also seen for lung cancer. Excluding lung cancer from the grouping of all solid cancers resulted in evidence of a linear association with external radiation dose (ERR/Sv = 0.24, 95% CI: 0.01; 0.49, based on 15,035 cases), so suggesting some degree of confounding by smoking. Statistically significantly increasing trends with dose were seen for cancers of the colorectal, bladder and pleura cancer. Some of these results should be treated with caution because of the limited corroborating evidence from other published studies. Information on internal doses as well as non-radiation factors such smoking would be helpful to make more definitive inferences.

Estimation of electron-specific absorbed fractions with the InterDosi code using ICRP adult female voxel-based phantom

The International Commission on Radiological Protection (ICRP) through its publications recommends the estimation of Specific Absorbed Fractions (SAFs) using voxelized phantoms in order to assess the doses internally absorbed by organs exposed to ionizing radiation. In the present work, we report a large set of SAFs calculated using the ICRP Adult Female (ICRP-AF) phantom. The new Geant4-based code called InterDosi version 1.0 was used to simulate monoenergetic electrons of 20 different energies, ranging from 0.005 to 10 MeV, emitted uniformly from 18 different source organs. In order to estimate SAFs in 169 target organs/regions, 360 Monte Carlo multithreaded simulations were run on 32 CPUs of the HPC-MARWAN-CNRST computing grid. The calculated SAFs were compared to the recent results obtained using GATE 8.1 code and published by the OpenDose collaboration. It is shown that the obtained results are in well-agreement with the reference values, with absolute discrepancies less than 0.6% for a self-absorption condition and less than 5% in almost all energies for a cross-absorption condition. We concluded that InterDosi code might be used for dosimetry of internal electron emitters.

Разработка и тестирование модели поглощения энергии в биообъектах от инкорпорированных излучателей фотонов

A new analytical method, previously developed for estimating beta absorbed fractions, was ex-tended for analytical estimating photon absorbed fractions in soft-tissue bodies from internal uni-formly distributed gamma emitters. The method involves a rescaling procedure with transfor-mation of real biological sizes to unitless effective ones combining information of both photon energy and object’s size. The rescaling was applied to large published datasets of photon ab-sorbed fractions in soft-tissue spheres. A new effect was demonstrated: the rescaled data were united into a single smooth “universal curve” with saturation. The universal curve for photon ab-sorbed fractions was described analytically as a function of a single argument – a rescaled effec-tive radius. Practical applicability of the approach for non-spherical convex bodies (ellipsoids) was demonstrated. Examples of analytical estimating the internal dose coefficients for repre-sentative terrestrial animals were calculated. The new method now available for electron and photon internal dosimetry, provides an effective analytical tool for calculating radiation absorbed fractions in organs and bodies of soft-tissue organisms.

Review of the Geant4-DNA Simulation Toolkit for Radiobiological Applications at the Cellular and DNA Level.

Simple SummaryA brief description of the methodologies to simulate ionizing radiation transport in biologically relevant matter is presented. Emphasis is given to the physical, chemical, and biological models of Geant4-DNA that enable mechanistic radiobiological modeling at the cellular and DNA level, important to improve the efficacy of existing and novel radiotherapeutic modalities for the treatment of cancer.The Geant4-DNA low energy extension of the Geant4 Monte Carlo (MC) toolkit is a continuously evolving MC simulation code permitting mechanistic studies of cellular radiobiological effects. Geant4-DNA considers the physical, chemical, and biological stages of the action of ionizing radiation (in the form of x- and γ-ray photons, electrons and β±-rays, hadrons, α-particles, and a set of heavier ions) in living cells towards a variety of applications ranging from predicting radiotherapy outcomes to radiation protection both on earth and in space. In this work, we provide a brief, yet concise, overview of the progress that has been achieved so far concerning the different physical, physicochemical, chemical, and biological models implemented into Geant4-DNA, highlighting the latest developments. Specifically, the “dnadamage1” and “molecularDNA” applications which enable, for the first time within an open-source platform, quantitative predictions of early DNA damage in terms of single-strand-breaks (SSBs), double-strand-breaks (DSBs), and more complex clustered lesions for different DNA structures ranging from the nucleotide level to the entire genome. These developments are critically presented and discussed along with key benchmarking results. The Geant4-DNA toolkit, through its different set of models and functionalities, offers unique capabilities for elucidating the problem of radiation quality or the relative biological effectiveness (RBE) of different ionizing radiations which underlines nearly the whole spectrum of radiotherapeutic modalities, from external high-energy hadron beams to internal low-energy gamma and beta emitters that are used in brachytherapy sources and radiopharmaceuticals, respectively.

Combined cell and nanoparticle models for TOPAS to study radiation dose enhancement in cell organelles

Dose enhancement by gold nanoparticles (AuNP) increases the biological effectiveness of radiation damage in biomolecules and tissue. To apply them effectively during cancer therapy their influence on the locally delivered dose has to be determined. Hereby, the AuNP locations strongly influence the energy deposit in the nucleus, mitochondria, membrane and the cytosol of the targeted cells. To estimate these effects, particle scattering simulations are applied. In general, different approaches for modeling the AuNP and their distribution within the cell are possible. In this work, two newly developed continuous and discrete-geometric models for simulations of AuNP in cells are presented. These models are applicable to simulations of internal emitters and external radiation sources. Most of the current studies on AuNP focus on external beam therapy. In contrast, we apply the presented models in Monte-Carlo particle scattering simulations to characterize the energy deposit in cell organelles by radioactive 198AuNP. They emit beta and gamma rays and are therefore considered for applications with solid tumors. Differences in local dose enhancement between randomly distributed and nucleus targeted nanoparticles are compared. Hereby nucleus targeted nanoparticels showed a strong local dose enhancement in the radio sensitive nucleus. These results are the foundation for future experimental work which aims to obtain a mechanistic understanding of cell death induced by radioactive 198Au.

Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors

Cell-free secretomes represent a promising new therapeutic avenue in regenerative medicine, and γ-irradiation of human peripheral blood mononuclear cells (PBMCs) has been shown to promote the release of paracrine factors with high regenerative potential. Recently, the use of alternative irradiation sources, such as artificially generated β- or electron-irradiation, is encouraged by authorities. Since the effect of the less hazardous electron-radiation on the production and functions of paracrine factors has not been tested so far, we compared the effects of γ- and electron-irradiation on PBMCs and determined the efficacy of both radiation sources for producing regenerative secretomes. Exposure to 60 Gy γ-rays from a radioactive nuclide and 60 Gy electron-irradiation provided by a linear accelerator comparably induced cell death and DNA damage. The transcriptional landscapes of PBMCs exposed to either radiation source shared a high degree of similarity. Secretion patterns of proteins, lipids, and extracellular vesicles displayed similar profiles after γ- and electron-irradiation. Lastly, we detected comparable biological activities in functional assays reflecting the regenerative potential of the secretomes. Taken together, we were able to demonstrate that electron-irradiation is an effective, alternative radiation source for producing therapeutic, cell-free secretomes. Our study paves the way for future clinical trials employing secretomes generated with electron-irradiation in tissue-regenerative medicine.

VADER: a variable dose-rate external 137Cs irradiator for internal emitter and low dose rate studies

In the long term, 137Cs is probably the most biologically important agent released in many accidental (or malicious) radiation disasters. It can enter the food chain, and be consumed, or, if present in the environment (e.g. from fallout), can provide external irradiation over prolonged times. In either case, due to the high penetration of the energetic γ rays emitted by 137Cs, the individual will be exposed to a low dose rate, uniform, whole body, irradiation. The VADER (VAriable Dose-rate External 137Cs irradiatoR) allows modeling these exposures, bypassing many of the problems inherent in internal emitter studies. Making use of discarded 137Cs brachytherapy seeds, the VADER can provide varying low dose rate irradiations at dose rates of 0.1 to 1.2 Gy/day. The VADER includes a mouse “hotel”, designed to allow long term simultaneous residency of up to 15 mice. Two source platters containing ~ 250 mCi each of 137Cs brachytherapy seeds are mounted above and below the “hotel” and can be moved under computer control to provide constant low dose rate or a varying dose rate mimicking 137Cs biokinetics in mouse or man. We present the VADER design and characterization of its performance over 18 months of use.

Dose and Dose-Rate Effects in a Mouse Model of Internal Exposure from 137Cs. Part 2: Integration of Gamma-H2AX and Gene Expression Biomarkers for Retrospective Radiation Biodosimetry.

Inhalation and ingestion of 137Cs and other long-lived radionuclides can occur after large-scale accidental or malicious radioactive contamination incidents, resulting in a complex temporal pattern of radiation dose/dose rate, influenced by radionuclide pharmacokinetics and chemical properties. High-throughput radiation biodosimetry techniques for such internal exposure are needed to assess potential risks of short-term toxicity and delayed effects (e.g., carcinogenesis) for exposed individuals. Previously, we used γ-H2AX to reconstruct injected 137Cs activity in experimentally-exposed mice, and converted activity values into radiation doses based on time since injection and 137Cs-elimination kinetics. In the current study, we sought to assess the feasibility and possible advantages of combining γ-H2AX with transcriptomics to improve 137Cs activity reconstructions. We selected five genes (Atf5, Hist2h2aa2, Olfr358, Psrc1, Hist2h2ac) with strong statistically-significant Spearman's correlations with injected activity and stable expression over time after 137Cs injection. The geometric mean of log-transformed signals of these five genes, combined with γ-H2AX fluorescence, were used as predictors in a nonlinear model for reconstructing injected 137Cs activity. The coefficient of determination (R2) comparing actual and reconstructed activities was 0.91 and root mean squared error (RMSE) was 0.95 MBq. These metrics remained stable when the model was fitted to a randomly-selected half of the data and tested on the other half, repeated 100 times. Model performance was significantly better when compared to our previous analysis using γ-H2AX alone, and when compared to an analysis where genes are used without γ-H2AX, suggesting that integrating γ-H2AX with gene expression provides an important advantage. Our findings show a proof of principle that integration of radiation-responsive biomarkers from different fields is promising for radiation biodosimetry of internal emitters.

Serum Metabolomic Alterations Associated with Cesium-137 Internal Emitter Delivered in Various Dose Rates.

Our laboratory and others have use radiation metabolomics to assess responses in order to develop biomarkers reflecting exposure and level of injury. To expand the types of exposure and compare to previously published results, metabolomic analysis has been carried out using serum samples from mice exposed to 137Cs internal emitters. Animals were injected intraperitoneally with 137CsCl solutions of varying radioactivity, and the absorbed doses were calculated. To determine the dose rate effect, serum samples were collected at 2, 3, 5, 7, and 14 days after injection. Based on the time for each group receiving the cumulative dose of 4 Gy, the dose rate for each group was determined. The dose rates analyzed were 0.16 Gy/day (low), 0.69 Gy/day (medium), and 1.25 Gy/day (high). The results indicated that at a cumulative dose of 4 Gy, the low dose rate group had the least number of statistically significantly differential spectral features. Some identified metabolites showed common changes for different dose rates. For example, significantly altered levels of oleamide and sphingosine 1-phosphate were seen in all three groups. On the other hand, the intensity of three amino acids, Isoleucine, Phenylalanine and Arginine, significantly decreased only in the medium dose rate group. These findings have the potential to be used in assessing the exposure and the biological effects of internal emitters.

DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1-1.2Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7days with total accumulated dose up to 2.7Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2Gy and ≥ 2Gy, highlighting the potential of γ-H2AX MFI as a biomarker fordosimetry in a protracted, environmental exposure scenario.

Assessment of self- and cross-absorbed SAF values for HDRK-man using Geant4 code: internal photon and electron emitters

The ultimate need to account for the partial amount of energy deposited in target tissue/organ resulting from internal inhalation, ingestion, and injection intakes of radionuclides, defined by the Medical Internal Radiation Dosimetry committee as the specific absorbed fraction (SAF), has become obvious. In this study, we assessed the SAF values for self- and cross-absorption, which were calculated for a uniform distribution of monoenergetic photon and electron emitters with energies ranging from 15 keV to 3 MeV. The voxelized human phantom “High-Definition Reference Korean-man” (HDRK-man), which was implemented using the Monte Carlo simulation code Geant4 (version 10.1), was used for several combinations of target–source organs. The results were compared to those of the International Commission on Radiological Protection Reference (ICRP133) and Zubal phantoms. It was found that the SAF values of the three models have a similar trend. However, the SAF values for the HDRK-man phantom were higher than those of the other two models, with a relatively good agreement with those for the ICRP133 phantom (differences of 13.9 ± 2.8 and 12.1 ± 3.2 for photon and electron emitters, respectively). To analyze the differences in SAF values, we calculated the chord length distributions (CLDs) for selected target–source combinations. The parameters of organ mass (or volume) and CLDs, in addition to the adopted computational procedures, mainly cause such discrepancies. For realistic radionuclide emission spectra, an overall overestimation was observed when computing the S values for three radiopharmaceuticals studied (I-131, In-111, and Lu-177) and for liver–spleen intra- and inter-organ absorption when compared with published data. The new arrangement of S and SAF values is expected to add value for multidisciplinary research and clinical communities.

Post-effects of radioactive decay in ligands on biologically active transport platforms

The electron capture consequences in the 57Co DOTA complex compound and processes of radiation-induced defect formation in DOTA under the effect of recoil nuclei produced after the α-decay of 241Am were studied using high performance liquid radiochromatography and emission Mössbauer spectroscopy. The experiments conducted have shown that the production of targeted RPHs on the base of alpha-emitters and when applying the conventional approach (biologically active molecular construct with any chelate carrying a radioactive tracer) is just a scientific mystification, since the recoiling alpha-emitting nucleus causes a destroying effect on the neighboring substrate molecules and entirely excludes the targeted transport of the preparation. This is a bold conclusion indeed. However, it is confirmed in part by the works of other authors and by the fact that the encapsulation of α-particle emitters in inorganic (rather than organic) nanocontainers significantly decreases the negative effect of recoil nuclei on the carrier molecule and allows radiation treatment to be done of cancerous tissues, which is similar to hadron therapy. It is the recoiling nuclei (and not at all the emitted alpha-particles) that possess a huge destroying ability and exert a therapeutic effect when conventional approach (biologically active molecular construct with any chelate carrying a alpha-emitters) are used. The amount of radiation-induced damage in a matrix, caused by a recoil nucleus with a typical energy of approximately 100 keV is by a factor of several hundreds higher than the amount caused by the 5–7 MeV α-particles. If a labelled molecular construction has reached the tumor cell, there is no doubt in the “prioritative” action of recoil nuclei as compared to that of α-particles. However, the picture changes dramatically if the recoil impact “is blocked” at the location where an α-particle is emitted (e.g., in inorganic nanocontainers). A success in the development and production of pharmaceutical forms based on alpha-emitters is possible only when the pernicious influence of recoil nuclei is “blocked” owing to a high radiation stability of labelled compounds or owing to other “means of transportation” of the radionuclides to lesions. A reasonable alternative to alpha-emitters might be Auger- and internal conversion electron emitters that possess (as it is shown by the present studies and, which is of more importance, by the worldwide radionuclide practice) by incomparably higher radiation stability of labelled compounds.

MPS dose reconstruction for internal emitters: some site-specific issues and approaches

Background As part of the Million Person Study (MPS), dose reconstructions for internal emitters have been performed for several U.S. facilities where large quantities of radionuclides were handled. The main challenges and dominant sources of potential error in retrospective dose estimates for internally exposed workers have been found to vary from site to site. This article discusses some important issues encountered in dose reconstructions performed for selected MPS sites and the approaches used to address those issues. The focus is on some foundational components of retrospective dose assessments that have received little attention in the literature. Methods The discussion is built around illustrative exposure data and dose reconstructions for workers at selected facilities addressed in the MPS. Related findings at some non-MPS sites are also discussed. Results Each of the following items has been found to be a major source of potential error in reconstructed tissue doses for some MPS sites: identification of all dosimetrically important internal emitters; the time pattern of intake; the mode(s) of intake; reliability of bioassay measurements; application of surrogate (coworker) information in lieu of, or in conjunction with, worker-specific monitoring data; the chemical and physical forms of inhaled radionuclides; and the relation of air monitoring data to actual intake. Conclusions (1) Much of the dose reconstruction effort for internal emitters should be devoted to development of best feasible exposure scenarios. (2) Coworker data should be used to assign exposure scenarios or dose estimates to workers with missing exposure data only if there is compelling evidence of similar coworker exposure. (3) Bioassay data for some radionuclides and periods of operation at MPS sites are of questionable reliability due to sizable uncertainties associated with contamination, recovery, or background issues. (4) Dose estimates derived solely from air monitoring data should be treated as highly uncertain values in the absence of site-specific information demonstrating that the data are reasonably predictive of intake. (5) For intakes known or assumed to be via inhalation, the uncertainty in lung dose typically is much greater than the uncertainty in dose to systemic tissues, when dose estimates are based on urinary excretion data. (6) The lung dose estimate often can be improved through development of site-specific respiratory absorption parameter values. (7) There is generally insufficient site-specific information to justify development of site-specific systemic models.

Potential improvements in brain dose estimates for internal emitters

Background Element-specific biokinetic models are used to reconstruct doses to systemic tissues from internal emitters. Typically, a systemic model for a radionuclide explicitly depicts only its dominant repositories. Remaining tissues and fluids are aggregated into a pool called Other tissue in which the radionuclide is assumed to be uniformly distributed. In the systemic biokinetic models used in radiation protection, the brain usually is addressed as an implicit mass fraction of Other tissue rather than an explicitly depicted repository. Due to increasing interest in radiation effects on the brain, efforts are underway to improve brain dosimetry for internal radiation sources. Methods We assessed potential improvements in brain dosimetry for internal emitters by explicitly modeling brain kinetics rather than treating the brain as a mass fraction of Other tissue. We selected 10 elements for which brain kinetics can be modeled using published biokinetic data. Injection dose coefficients were calculated for a relatively long-lived radioisotope of each element using each of two versions of the ICRP’s latest systemic biokinetic model for the element, the original version and a modified version differing only in the treatment of brain. If the ICRP model contained an explicit brain pool, the modified version depicted brain instead as a mass fraction of Other tissue. If the ICRP model included brain in Other tissue, the modified version included an explicit brain pool with kinetics based on best available brain-specific data. Results The result for a given radionuclide is expressed as a ratio A:B, where A and B are the dose coefficients based on the versions of the model with and without an explicit brain pool, respectively. The following ratios A:B were obtained for the 10 radionuclides addressed here: 241Am, 0.13; 207Bi, 0.57; 234U, 0.81; 239Pu, 0.96; 203Hg (vapor), 1.4; 134Cs, 1.5; 54Mn, 1.7; 210Po, 1.7; 226Ra, 1.9; 210Pb, 3.3. These ratios indicate that a dose estimate for brain based on a biokinetic model with brain implicitly contained in Other tissue may substantially underestimate or substantially overestimate a dose estimate that reflects best available brain-specific biokinetic data. Of course, the reliability of the latter estimate depends on the quality of the underlying biokinetic data. Conclusions Where feasible, the brain should be depicted explicitly in biokinetic models used in epidemiological studies addressing adverse effects of ionizing radiation.