Low-energy Auger Electrons Research Articles

Determination of 93Mo in Radioactive Samples of Sulfuric Acid Media from Nuclear Facilities.

93Mo is an important radionuclide in view of radioactive waste repository because of its long half-life and high mobility in the environment. 93Mo decays by electron capture without any measurable gamma ray emission. The concentration of 93Mo in most of the radioactive waste is many orders of magnitude lower than the major activation product radionuclides, which makes the accurate determination of 93Mo a big challenge. A new analytical method for the determination of 93Mo in sulfuric acid media from nuclear power reactor was developed. 93Mo was separated from most of the radionuclides by cation exchange chromatography followed by the removal of sulfate by CaSO4 precipitation. A further purification of 93Mo, especially from anion species of 51Cr and 125Sb, was achieved by anion exchange chromatography and a short alumina column separation. The chemical yield of 93Mo in the entire separation procedure reached about 75%, and the decontamination factors for all potential interfering radionuclides were 1.5 × 106-1.6 × 108. The purified 93Mo was measured by liquid scintillation counting through counting its low-energy Auger electrons. A detection limit of 2 mBq/g for 93Mo in 50 g sample was achieved by this method, which enables the quantitative determination of 93Mo in most of the radioactive samples in the decommissioning waste and coolant water of nuclear power reactors. The developed method has been successfully applied to determine 93Mo in coolant water of nuclear power reactors, providing a robust analytical approach of 93Mo for the radiological characterization of radioactive wastes.

How to explain the sensitivity of DNA double-strand breaks yield to 125I position?

Purpose Auger emitters exhibit interesting features due to their emission of a cascade of short-range Auger electrons. Maximum DNA breakage efficacy is achieved when decays occur near DNA. Studies of double-strand breaks (DSBs) yields in plasmids revealed cutoff distances from DNA axis of 10.5 Å–12 Å, beyond which the mechanism of DSBs moves from direct to indirect effects, and the yield decreases rapidly. Some authors suggested that the average energy deposited in a DNA cylinder could explain such cutoffs. We aimed to study this hypothesis in further detail. Materials and methods Using the Monte Carlo code CELLDOSE, we investigated the influence of the 125I atom position on energy deposits and absorbed doses per decay not only in a DNA cylinder, but also in individual strands, each modeled as 10 spheres encompassing the fragility sites for phosphodiester bond cleavage. Results The dose per decay decreased much more rapidly for a sphere in the proximal strand than for the DNA cylinder. For example, when moving the 125I source from 10.5 Å to 11.5 Å, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder. Conclusions Explaining variations in DSBs yields with 125I position should consider the probability of inducing damage in the proximal strand (nearest to the 125I atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4π) emission of 125I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.

Requirements for Designing an Effective Metallic Nanoparticle (NP)-Boosted Radiation Therapy (RT).

Simple SummaryRecent advances in nanotechnology gave rise to trials with various types of metallic nanoparticles (NPs) to enhance the radiosensitization of cancer cells while reducing or maintaining the normal tissue complication probability during radiation therapy. This work reviews the physical and chemical mechanisms leading to the enhancement of ionizing radiation’s detrimental effects on cells and tissues, as well as the plethora of experimental procedures to study these effects of the so-called “NPs’ radiosensitization”. The paper presents the need to a better understanding of all the phases of actions before applying metallic-based NPs in clinical practice to improve the effect of IR therapy. More physical and biological experiments especially in vivo must be performed and simulation Monte Carlo or mathematical codes based on more accurate models for all phases must be developed.Many different tumor-targeted strategies are under development worldwide to limit the side effects and improve the effectiveness of cancer therapies. One promising method is to enhance the radiosensitization of the cancer cells while reducing or maintaining the normal tissue complication probability during radiation therapy using metallic nanoparticles (NPs). Radiotherapy with MV photons is more commonly available and applied in cancer clinics than high LET particle radiotherapy, so the addition of high-Z NPs has the potential to further increase the efficacy of photon radiotherapy in terms of NP radiosensitization. Generally, when using X-rays, mainly the inner electron shells are ionized, which creates cascades of both low and high energy Auger electrons. When using high LET particles, mainly the outer shells are ionized, which give electrons with lower energies than when using X-rays. The amount of the produced low energy electrons is higher when exposing NPs to heavy charged particles than when exposing them to X-rays. Since ions traverse the material along tracks, and therefore give rise to a much more inhomogeneous dose distributions than X-rays, there might be a need to introduce a higher number of NPs when using ions compared to when using X-rays to create enough primary and secondary electrons to get the desired dose escalations. This raises the questions of toxicity. This paper provides a review of the fundamental processes controlling the outcome of metallic NP-boosted photon beam and ion beam radiation therapy and presents some experimental procedures to study the biological effects of NPs’ radiosensitization. The overview shows the need for more systematic studies of the behavior of NPs when exposed to different kinds of ionizing radiation before applying metallic-based NPs in clinical practice to improve the effect of IR therapy.

Bone tumor-targeted delivery of theranostic 195mPt-bisphosphonate complexes promotes killing of metastatic tumor cells.

Platinum-based drugs such as cisplatin are very potent chemotherapeutics, whereas radioactive platinum (195mPt) is a rich source of low-energy Auger electrons, which kills tumor cells by damaging DNA. Auger electrons damage cells over a very short range. Consequently, 195mPt-based radiopharmaceuticals should be targeted toward ​tumors to maximize radiotherapeutic efficacy and minimize Pt-based systemic toxicity. Herein, we show that systemically administered radioactive bisphosphonate-functionalized platinum (195mPt-BP) complexes specifically accumulate in intratibial bone metastatic lesions in mice. The 195mPt-BP complexes accumulate 7.3-fold more effectively in bone 7 days after systemic delivery compared to 195mPt-cisplatin lacking bone-targeting bisphosphonate ligands. Therapeutically, 195mPt-BP treatment causes 4.5-fold more γ-H2AX formation, a biomarker for DNA damage in metastatic tumor cells compared to 195mPt-cisplatin. We show that systemically administered 195mPt-BP is radiotherapeutically active, as evidenced by an 11-fold increased DNA damage in metastatic tumor cells compared to non-radioactive Pt-BP controls. Moreover, apoptosis in metastatic tumor cells is enhanced more than 3.4-fold upon systemic administration of 195mPt-BP vs. radioactive 195mPt-cisplatin or non-radioactive Pt-BP controls. These results provide the first preclinical evidence for specific accumulation and strong radiotherapeutic activity of 195mPt-BP in bone metastatic lesions, which offers new avenues of research on radiotherapeutic killing of tumor cells in bone metastases by Auger electrons.

Electron track structure simulations in a gold nanoparticle using Geant4-DNA

Gold Nanoparticles (GNPs) have recently gained a lot of attention due to their potential benefit to improve the efficacy of X-ray radiotherapy. Owing to their high atomic number, GNPs are able to absorb higher quantities of incident radiation with respect to the surrounding tissue, producing, in particular, photoelectrons and low energy Auger electrons. These additional low energy electrons increase the local energy deposition in the region surrounding the GNP. Monte Carlo simulations play a key role in the investigation of GNP radio-enhancement and it is widely recognised that track structure physics models are the state-of-the-art for nano-scale studies.In 2016, we have developed track structure physics models for the Geant4-DNA toolkit allowing electron transport for microscopic bulk gold (Geant4_DNA_AU_2016) and we have recently improved them in the low energy domain (Geant4_DNA_AU_2018).In this paper, we report the benchmarking of these newly developed physics models when calculating the physical dose and the Dose Enhancement Factor (DEF) around a GNP. We demonstrate that Geant4_DNA_AU_2018 models give similar azimuthal distribution of two dimensional absorbed dose around a single GNP, but result in larger absorbed dose and DEF than Geant4_DNA_AU_2016 models. In parallel, we investigated the performance of a newly developed multiple scattering model in Geant4 based on the Goudsmit-Saunderson (GS) model, when used together with the electromagnetic physics models with the Geant4 Livermore condensed-history approach. Our results show that the GS model does not affect the results of the simulations when studying GNP radio-enhancement with a condensed-history approach.

Re-assessing gallium-67 as a therapeutic radionuclide

Abstract Introduction Despite its desirable half-life and low energy Auger electrons that travel further than for other radionuclides, 67 Ga has been neglected as a therapeutic radionuclide. Here, 67 Ga is compared with Auger electron emitter 111 In as a potential therapeutic radionuclide. Methods Plasmid pBR322 studies allowed direct comparison between 67 Ga and 111 In (1MBq) in causing DNA damage, including the effect of chelators (EDTA and DTPA) and the effects of a free radical scavenger (DMSO). The cytotoxicity of internalized (by means of delivery in the form of oxine complexes) and non-internalized 67 Ga and 111 In was measured in DU145 prostate cancer cells after a one-hour incubation using cell viability (trypan blue) and clonogenic studies. MDA-MB-231 and HCC1954 cells were also used. Results Plasmid DNA damage was caused by 67 Ga and was comparable to that caused by 111 In; it was reduced in the presence of EDTA, DTPA and DMSO. The A 50 values (internalized activity of oxine complexes per cell required to kill 50% of cells) as determined by trypan blue staining was 1.0Bq/cell for both 67 Ga and 111 In; the A 50 values determined by clonogenic assay were 0.7Bq/cell and 0.3Bq/cell for 111 In and 67 Ga respectively. At the concentrations required to achieve these uptake levels, non-internalized 67 Ga and 111 In caused no cellular toxicity. Qualitatively similar results were found for MDA-MB-231 and HCC1954 cells. Conclusion 67 Ga causes as much damage as 111 In to plasmid DNA in solution and shows similar toxicity as 111 In at equivalent internalized activity per cell. 67 Ga therefore deserves further evaluation for radionuclide therapy. Advances in knowledge and implications for patient care The data presented here is at the basic level of science. If future in vivo and clinical studies are successful, 67 Ga could become a useful radionuclide with little healthy tissue toxicity in the arsenal of weapons for treating cancer.

Re-assessing gallium-67 as a therapeutic radionuclide

IntroductionDespite its desirable half-life and low energy Auger electrons that travel further than for other radionuclides, 67Ga has been neglected as a therapeutic radionuclide. Here, 67Ga is compared with Auger electron emitter 111In as a potential therapeutic radionuclide. MethodsPlasmid pBR322 studies allowed direct comparison between 67Ga and 111In (1MBq) in causing DNA damage, including the effect of chelators (EDTA and DTPA) and the effects of a free radical scavenger (DMSO). The cytotoxicity of internalized (by means of delivery in the form of oxine complexes) and non-internalized 67Ga and 111In was measured in DU145 prostate cancer cells after a one-hour incubation using cell viability (trypan blue) and clonogenic studies. MDA-MB-231 and HCC1954 cells were also used. ResultsPlasmid DNA damage was caused by 67Ga and was comparable to that caused by 111In; it was reduced in the presence of EDTA, DTPA and DMSO. The A50 values (internalized activity of oxine complexes per cell required to kill 50% of cells) as determined by trypan blue staining was 1.0Bq/cell for both 67Ga and 111In; the A50 values determined by clonogenic assay were 0.7Bq/cell and 0.3Bq/cell for 111In and 67Ga respectively. At the concentrations required to achieve these uptake levels, non-internalized 67Ga and 111In caused no cellular toxicity. Qualitatively similar results were found for MDA-MB-231 and HCC1954 cells. Conclusion67Ga causes as much damage as 111In to plasmid DNA in solution and shows similar toxicity as 111In at equivalent internalized activity per cell. 67Ga therefore deserves further evaluation for radionuclide therapy. Advances in knowledge and implications for patient careThe data presented here is at the basic level of science. If future in vivo and clinical studies are successful, 67Ga could become a useful radionuclide with little healthy tissue toxicity in the arsenal of weapons for treating cancer.

Small scale radiopharmaceutical dosimetry

Nuclear medicine uses radiations with highly variable ranges: for photons emissions, the range to be studied is that of the whole body. Electrons/beta have a range of some mm or less, alpha have usually a range inferior to 100 μm. Low energy Auger electrons deposit their energy within some nm. The relationship between particle range and the scale of the biologic structure of interest conditions the type of dosimetric study to implement. In a context of therapeutic nuclear medicine, radiopharmaceutical dosimetry is implemented at various scales for different reasons: • At the cellular scale, the objective is to understand the radiobiology of ionizing radiations and to document the absorbed dose – effect relationship. • Small animal dosimetry is usually performed during preclinical experiments to test the potential of new radiopharmaceuticals. • Clinical dosimetry is implemented to document and optimize molecular radiotherapy. We will present various preclinical dosimetric approaches (cell/small animals) implemented in a context of molecular radiotherapy.

Enhancement of DNA double-strand break induction and cell killing by K-shell absorption of phosphorus in human cell lines

Purpose: To investigate an enhancement of DNA double-strand break (DSB) induction and cell killing effect by K-shell ionization of phosphorus atoms and Auger electrons on human cell lines.Materials and methods: Induction of DSB, DNA damage responses, cell cycle distributions, and cell killing effects were investigated after exposures of the cells with monochromatic synchrotron radiation soft X-rays of 2153 and 2147 eV, which were the resonance peak and off peak, respectively, of the K-shell photoabsorption of phosphorus.Results: Higher biological effects in the cells irradiated with soft X-rays at 2153 eV than at 2147 eV were observed in (i) the efficiency of 53BP1/γ-H2AX co-localized foci formation per dose and residual number of foci, (ii) prolonged phosphorylation levels of DSB repair and/or cell cycle checkpoint related proteins and G2 arrest, (iii) the cell killing effects at the 10% survival level of normal human fibroblasts, HeLa cells, and human glioblastoma M059K cells (1.2–1.5 times higher) and that of human ataxia telangiectasia mutated (ATM)-defective cells and glioblastoma DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-defective cells (1.2 times).Conclusion: The yield of DSB and partly less-reparable complex DNA damage induction in human cells was enhanced by K-shell photoabsorption of phosphorus and low-energy Auger electrons.

Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI

Purpose: In addition to gamma radiation, 99mTc emits low-energy Auger electrons with path-lengths of nanometers to micrometers that cannot be utilized for diagnostic procedures; however, they have frequently been discussed for therapeutic applications. We compared radiotoxicity of three 99mTc-labeled radiopharmaceuticals with differences in the subcellular distribution.Materials and methods: The intracellular radionuclide uptake and subcellular distribution of [99mTc]-pertechnetate (99mTc-pertechnetate), [99mTc]Tc-hexamethyl-propylene-aminoxime (99mTc-HMPAO) and [99mTc]Tc-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) were quantified in rat thyroid FRTL-5 cells. Radiotoxicity was compared using late phosphorylated histone H2AX (γH2AX) foci as a marker for unrepaired DNA double-strand breaks (DNA-DSB) and clonogenic cell survival.Results: 99mTc-HMPAO showed a substantially higher uptake into the nucleus and the membrane/organelles than 99mTc-pertechnetate or 99mTc-MIBI. The colony-forming assay showed that 99mTc-pertechnetate and 99mTc-HMPAO caused a similar reduction in cell survival. 99mTc-MIBI is less radiotoxic in terms of the estimated nucleus dose and induced the fewest number of γH2AX foci compared with the other 99mTc-tracers, and 99mTc-HMPAO induced a fewer number of γH2AX foci than 99mTc-pertechnetate.Conclusions: Our findings reveal that clonogenic cellular survival is not solely determined by the DNA-DSB response. This finding may suggest the involvement of extra-nuclear radiosensitive targets in cell inactivation. For example, the mitochondria or the cell membrane could be affected by 99mTc-HMPAO.

Iodine-125-labeled DNA-Triplex-forming oligonucleotides reveal increased cyto- and genotoxic effectiveness compared to Phosphorus-32

Purpose: The efficacy of DNA-targeting radionuclide therapies might be strongly enhanced by employing short range particle-emitters. However, the gain of effectiveness is not yet well substantiated. We compared the Auger electron emitter I-125 to the ß−-emitter P-32 in terms of biological effectiveness per decay and radiation dose when located in the close proximity to DNA using DNA Triplex-forming oligonucleotides (TFO). The clonogenicity and the induction of DNA double-strand breaks (DSB) were investigated in SCL-II cells after exposure to P-32- or I-125-labeled TFO targeting the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene and after external homogeneous exposure to gamma-rays as reference radiation. Materials and methods: TFO were labeled with P-32 or I-125 using the primer extension method. Cell survival was analyzed by colony-forming assay and DNA damage was assessed by microscopic quantification of protein 53 binding protein 1 (53BP1) foci in SCL-II cells. Results: I-125-TFO induced a pronounced decrease of cell survival (D37 at ∼360 accumulated decays per cell, equivalent to 1.22 Gy cell nucleus dose) and a significant increase of 53BP1 foci with increasing decays. The P-32-labeled TFO induced neither a strong decrease of cell survival nor an increase of 53BP1 foci up to ∼4000 accumulated decays per cell, equivalent to ∼1 Gy cell nucleus dose. The RBE for I-125-TFO was in the range of 3–4 for both biological endpoints. Conclusions: I-125-TFO proved to be much more radiotoxic than P-32-TFO per decay and per unit dose although targeting the same sequence in the GAPDH gene. This might be well explained by the high number of low energy Auger electrons emitted by I-125 per decay, leading to a high ionization density in the immediate vicinity of the decay site, probably producing highly complex DNA lesions overcharging DNA repair mechanisms.

Abstract 1807: Nuclear targeted gold nanoparticles for radiation enhancement

Abstract Gold nanoparticles (AuNP) have been shown to enhance radiation dose (Hainfeld et al, 2004) resulting in significant improvement in tumor control (Hainfeld et al 2008, 2010, 2012). AuNPs that target nuclear DNA have the potential to greatly improve such radiation dose enhancement due to the utilization of the cascade of low energy Auger electrons that follow x-ray absorption. If the AuNP binds to the DNA, these high LET electrons should greatly augment double strand breaks and tumor cell killing. While positively charged peptides are known to take NP into the cell nucleus, they are expensive and subject to proteolytic degradation. We reasoned that just putting a positive charge on the AuNP might mimic enhanced cellular uptake, endothelial escape and nuclear translocation. Such three nm AuNPs had high cell uptake but were retained in the endosome with none getting into the nucleus whereas one nm positively charged AuNPs were found in the cell nucleus and nuclear membrane as well as the cytoplasm as evidenced by light and electron microscopy. Nuclear-localized positively charged AuNPs were found predominantly over regions of heterochromatin. Cells incubated with positively charged AuNPs in vitro and then irradiated showed an increased number of H2AX binding sites as evidenced by fluorescence. Cell metabolism assays using MTT, a surrogate for cell viability, performed one, two and three days following radiation therapy, showed that cells irradiated after loading with positively charged, nuclear targeted AuNPs manifested some decrease in cell viability. Citation Format: James F. Hainfeld, Henry M. Smilowitz. Nuclear targeted gold nanoparticles for radiation enhancement. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1807. doi:10.1158/1538-7445.AM2015-1807

Valence Auger decay following3sphotoionization in potassium

We have studied photoionization in the inner valence $3s$ subshell of K and the spectroscopic properties of the two $3{s}^{\ensuremath{-}1}\phantom{\rule{0.28em}{0ex}}(^{1}S)$ and $(^{3}S)$ resulting states. Similar to the Rb and Cs cases, the lifetime widths of the $(^{1}S)$ and $(^{3}S)$ states are found to be markedly different, due to the electron correlation effects. The main part of the study deals with the subsequent Auger decay of the $3{s}^{\ensuremath{-}1}$ states, which have the particularity to involve low energy $(\ensuremath{\sim}5\phantom{\rule{0.16em}{0ex}}\mathrm{eV})$ Auger electrons. A magnetic bottle spectrometer with a multicoincidence technique has been used to observe and filter the Auger spectra with respect to the ${\mathrm{K}}^{2+}$ final state. The evolution of these Auger spectra has been investigated near the ionization threshold. They show strong post-collision interaction (PCI) effects, which are well reproduced by semiclassical and eikonal models. They reveal the importance of the photoelectron--Auger-electron interaction associated with these low energy Auger electrons.

A novel 83mKr tracer method for characterizing xenon gas and cryogenic distillation systems

The radioactive isomer 83mKr, has many properties that make it very useful for various applications. Its low energy decay products, like conversion, shake-off and Auger electrons as well as X- and γ-rays are used for calibration purposes in neutrino mass experiments and direct dark matter detection experiments. Thanks to the short half-life of 1.83 h and the decay to the ground state 83Kr, one does not risk contamination of any low-background experiment with long-lived radionuclides. In this paper, we present a new approach, using 83mKr as a radioactive tracer in noble gases. A method of doping 83mKr, into xenon gas and its detection, using special custom-made detectors, based on a photomultiplier tube, is described. Two applications of this method are presented: firstly, it can be used to characterize the particle flow inside of gas routing systems and determine the circulation speed of gas particles inside of a gas purification system for xenon. Secondly, it is used for rapid estimating of the separation performance of a distillation system.

⁹⁹mTc pyrene derivative complex causes double-strand breaks in dsDNA mainly through cluster-mediated indirect effect in aqueous solution.

Radiation therapy for cancer patients works by ionizing damage to nuclear DNA, primarily by creating double-strand breaks (DSB). A major shortcoming of traditional radiation therapy is the set of side effect associated with its long-range interaction with nearby tissues. Low-energy Auger electrons have the advantage of an extremely short effective range, minimizing damage to healthy tissue. Consequently, the isotope 99mTc, an Auger electron source, is currently being studied for its beneficial potential in cancer treatment. We examined the dose effect of a pyrene derivative 99mTc complex on plasmid DNA by using gel electrophoresis in both aqueous and methanol solutions. In aqueous solutions, the average yield per decay for double-strand breaks is 0.011±0.005 at low dose range, decreasing to 0.0005±0.0003 in the presence of 1 M dimethyl sulfoxide (DMSO). The apparent yield per decay for single-strand breaks (SSB) is 0.04±0.02, decreasing to approximately a fifth with 1 M DMSO. In methanol, the average yield per decay of DSB is 0.54±0.06 and drops to undetectable levels in 2 M DMSO. The SSB yield per decay is 7.2±0.2, changing to 0.4±0.2 in the presence of 2 M DMSO. The 95% decrease in the yield of DSB in DMSO indicates that the main mechanism for DSB formation is through indirect effect, possibly by cooperative binding or clustering of intercalators. In the presence of non-radioactive ligands at a near saturation concentration, where radioactive Tc compounds do not form large clusters, the yield of SSB stays the same while the yield of DSB decreases to the value in DMSO. DSBs generated by 99mTc conjugated to intercalators are primarily caused by indirect effects through clustering.

99mTc-labeled HYNIC-DAPI causes plasmid DNA damage with high efficiency.

99mTc is the standard radionuclide used for nuclear medicine imaging. In addition to gamma irradiation, 99mTc emits low-energy Auger and conversion electrons that deposit their energy within nanometers of the decay site. To study the potential for DNA damage, direct DNA binding is required. Plasmid DNA enables the investigation of the unprotected interactions between molecules and DNA that result in single-strand breaks (SSBs) or double-strand breaks (DSBs); the resulting DNA fragments can be separated by gel electrophoresis and quantified by fluorescent staining. This study aimed to compare the plasmid DNA damage potential of a 99mTc-labeled HYNIC-DAPI compound with that of 99mTc pertechnetate (99mTcO4 −). pUC19 plasmid DNA was irradiated for 2 or 24 hours. Direct and radical-induced DNA damage were evaluated in the presence or absence of the radical scavenger DMSO. For both compounds, an increase in applied activity enhanced plasmid DNA damage, which was evidenced by an increase in the open circular and linear DNA fractions and a reduction in the supercoiled DNA fraction. The number of SSBs elicited by 99mTc-HYNIC-DAPI (1.03) was twice that caused by 99mTcO4 − (0.51), and the number of DSBs increased fivefold in the 99mTc-HYNIC-DAPI-treated sample compared with the 99mTcO4 − treated sample (0.02 to 0.10). In the presence of DMSO, the numbers of SSBs and DSBs decreased to 0.03 and 0.00, respectively, in the 99mTcO4 – treated samples, whereas the numbers of SSBs and DSBs were slightly reduced to 0.95 and 0.06, respectively, in the 99mTc-HYNIC-DAPI-treated samples. These results indicated that 99mTc-HYNIC-DAPI induced SSBs and DSBs via a direct interaction of the 99mTc-labeled compound with DNA. In contrast to these results, 99mTcO4 − induced SSBs via radical formation, and DSBs were formed by two nearby SSBs. The biological effectiveness of 99mTc-HYNIC-DAPI increased by approximately 4-fold in terms of inducing SSBs and by approximately 10-fold in terms of inducing DSBs.

99mTcO4−-, Auger-Mediated Thyroid Stunning: Dosimetric Requirements and Associated Molecular Events

Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4 −) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4 − required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4 −–mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects.

3d photoionization and subsequent decay of atomic gallium

We present an experimental and theoretical study of 3d photoionization and subsequent Auger decay of atomic gallium. The synchrotron radiation-induced electron spectra have been compared and analysed using multiconfiguration Dirac–Fock calculations. It has been shown that the theoretically predicted photoelectron spectrum is in rather good agreement with the experiment allowing us to identify the main spectral features. However, prediction of the Auger decay intensities fails due to calculational difficulties for the continuum wavefunctions of very low kinetic energy Auger electrons.

Determination of 41Ca with LSC and AMS: method development, modifications and applications

Despite the emission of only low energy Auger electrons (ca. 3.6 keV) and the difficulty of obtaining a certified standard, Liquid scintillation counting (LSC) determinations are still reasonable options for a radioanalytical laboratory involved in nuclear installation decommission. Besides, accelerator mass spectrometry (AMS), being the most sensitive analytical technique not only for 41Ca, is gaining increasingly broader accessibility and applicability. Herein, we present a radiochemical separation procedure developed for 41Ca determination with LSC and AMS in varying materials (i.e. water, concrete, sediment, soil, and biota). The radioanalytical isolation consists of anion exchange and extraction chromatography as well as carbonate precipitation and recrystallization from organic solvents. Thereby, interfering radionuclides as 55Fe, 60Co, 152Eu, U or actinides are removed with decontamination factors of 102–104. Quench curves for determining the measurement efficiency is generated with a 41Ca solution gained from the 41Ca/40Ca certified reference material ERM-AE701. In routine application the procedure is characterized by chemical yields of 67–86 %, measurement efficiencies of 1–10 % and detection limits of 0.05 Bq g−1 and 0.3 Bq L−1. Aliquots of the digestion solutions of LSC can be easily converted into CaF2–AMS targets by successive oxsalate and fluoride precipitation. Pros and cons for both measurement techniques are addressed based on 41Ca results from LSC and AMS for the same material.

Theory of laser-assisted Auger processes generated by ultrashort XUV pulses in atoms

A non-stationary quantum mechanical theory of the laser-assisted Auger process in atoms excited by an ultrashort (attosecond) electromagnetic pulse in the field of a few-cycle strong optical laser pulse is considered. The theory is based on numerically solving the time-dependent Schrödinger equation describing Auger decay. An approach is suggested which can be applied for the case of low-energy Auger electrons when it is necessary to take accurately into account the electron interaction with both the laser field and the field of the residual ion. We show that the amplitude of the process can be presented as a coherent sum of contributions from the corresponding Auger decays at consecutive moments of time. This presentation saves considerable computer time in numerical calculations of the Auger spectrogram. It also demonstrates that the Auger electrons emitted at different moments are coherent. As an example, the electron spectra for laser-assisted Auger decay are calculated for the MNN transition in Kr. The variation of the Auger spectra with time delay between the two pulses is discussed. The results are compared with those obtained within the strong-field approximation.