WorldWideScience

Sample records for astatination

  1. Bibliography of astatine chemistry and biomedical applications

    International Nuclear Information System (INIS)

    An overall bibliography is presented on astatine chemistry and on the biomedical applications of its 211At isotope. The references were grouped in the following chapters: General reviews; Discovery, Natural Occurence; Nuclear Data; Preparation, Handling, Radiation Risk; Physico-chemical Properties; Astatine Compounds and Chemical Reactions; Biological Effects and Applications. Entries are sorted alphabetically by authors name in each chapter, and cross-references to other chapters are provided if appropriate. (R.P.)

  2. Astatine-211: production and availability.

    Science.gov (United States)

    Zalutsky, Michael R; Pruszynski, Marek

    2011-07-01

    The 7.2-h half life radiohalogen (211)At offers many potential advantages for targeted α-particle therapy; however, its use for this purpose is constrained by its limited availability. Astatine-211 can be produced in reasonable yield from natural bismuth targets via the (209)Bi(α,2n)(211)At nuclear reaction utilizing straightforward methods. There is some debate as to the best incident α-particle energy for maximizing 211At production while minimizing production of (210)At, which is problematic because of its 138.4-day half life α-particle emitting daughter, (210)Po. The intrinsic cost for producing (211)At is reasonably modest and comparable to that of commercially available (123)I. The major impediment to (211)At availability is attributed to the need for a medium energy α-particle beam for its production. On the other hand, there are about 30 cyclotrons in the world that have the beam characteristics required for (211)At production. PMID:22201707

  3. Adsorption interaction of astatine species with quartz and gold surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Serov, A. [Paul Scherrer Institute, Villigen (Switzerland). Lab. for Radiochemistry and Environmental Chemistry; Bern Univ. (Switzerland). Dept. for Chemistry and Biochemistry; Aksenov, N.; Bozhikov, G. [Joint Institute for Nuclear Research, Dubna (RU). Flerov Lab. of Nuclear Reactions] (and others)

    2011-07-01

    The adsorption interaction of various astatine species with quartz and gold surfaces was investigated by gas chromatography methods. Due to variations of the redox potential of the carrier gas elemental astatine, astatine oxide and hypo-astatic acid have been produced. The identification of the astatine compounds is based on the analogy assumption to the gas phase chemistry of the closest homologues in group 17 of the periodic table, iodine and bromine. The deposition temperatures as well as enthalpies of adsorption have been determined for the astatine species. The enhancement of the metallic character within group 17 towards higher Z is clearly confirmed. Macroscopic properties (sublimation enthalpy) of previously unstudied AtO{sub 2} and HAtO were estimated. The determined data for elemental astatine were compared to available literature data. Based on the obtained experimental results possible designs of experiments for studying of chemical properties of the recently discovered element 117 can be suggested. (orig.)

  4. Recent advances in the organic chemistry of astatine

    International Nuclear Information System (INIS)

    Investigation on the chemical behaviour of astatine in the last decade are surveyed. The survey covers the physical and chemical properties of astatine, synthesis and identification of organic astatine compounds, their physicochemical properties. A special chapter is devoted to biomedical applications, including inorganic 211At species, 211At-labelled proteins and drugs. An extensive bibliography of the related literature is given. (N.T.) 129 refs.; 12 figs.; 14 tabs

  5. Discovery of the astatine, radon, francium, and radium isotopes

    CERN Document Server

    Fry, C

    2012-01-01

    Currently, thirty-nine astatine, thirty-nine radon, thirty-five francium, and thirty-four radium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  6. Extraction of astatine isotopes for development of radiopharmaceuticals using a 211Rn-211At generator

    International Nuclear Information System (INIS)

    In order to utilize a 211At isotope, a promising α-emitter for radionuclide therapy, the chemical properties of astatine isotopes are studied. We have examined wet chemistry methods through the distribution ratios of astatine in liquid-liquid extraction. The astatine isotopes have been found to be well extracted into DIPE and MIBK. We observed that the distribution ratio of astatine isotopes increases with concentrations of HCl greater than 3 M, while it decreases with the HCl concentration less than 2 M. The results will be useful for development of the 211Rn-211At generator. (author)

  7. Astatine-211-Labeled Targeted Radiotherapeutics: An Update

    International Nuclear Information System (INIS)

    The heavy halogen 211At was first proposed for use in α-particle targeted radiotherapy more than 30 years ago and continues to be one of the most promising radionuclides for this purpose. Although its 7.2-h half life is not ideal for intravenously administered whole antibodies, it is compatible with the pharmacokinetics of antibody fragments, peptides, aptamers and organic molecules. Its diverse chemistry allows its incorporation into a wide array of targeting vehicles, relying on its chemical similarity to iodine to provide a useful point of departure. On the other hand, the relatively low carbon-astatine bond strength is challenging. In common with the other α-emitters being discussed at this symposium, lack of reliable availability is one of the biggest hurdles in the use of 211At for targeted radiotherapy. However, in the case of 211At, it is not a question of production cost or availability of target material, because 211At can be produced in reasonable yield from natural bismuth targets. Rather, the difficulty is the lack of cyclotrons equipped with the medium energy α-particle beams required for its production. If the infrastructure for producing 211At is to be improved to the stage where 211At-labeled radiopharmaceuticals can have a meaningful impact, several developments must occur. First, the ability to produce clinically relevant levels of 211At that can be shipped to remote locations in chemically tractable form must be demonstrated. Approaches under consideration include compensating for radiolysis-mediated effects and the consideration of alternative chemistries. Second, strategies for compensating for heterogeneities in dose deposition must be developed, hopefully in a way that is compatible with approval for human use. And third, it is essential that more clinical trials be performed with 211At-labeled therapeutics, particularly in settings of minimum residual disease where the radiobiological advantages of α-particles can be best exploited. Our

  8. Measurement of the first ionization potential of astatine by laser ionization spectroscopy

    CERN Document Server

    Rothe, S; Antalic, S; Borschevsky, A; Capponi, L; Cocolios, T E; De Witte, H; Eliav, E; Fedorov, D V; Fedosseev, V N; Fink, D A; Fritzsche, S; Ghys, L; Huyse, M; Imai, N; Kaldor, U; Kudryavtsev, Yu; Köster, U; Lane, J; Lassen, J; Liberati, V; Lynch, K M; Marsh, B A; Nishio, K; Pauwels, D; Pershina, V; Popescu, L; Procter, T J; Radulov, D; Raeder, S; Rajabali, M M; Rapisarda, E; Rossel, R E; Sandhu, K; Seliverstov, M D; Sjödin, A M; Van den Bergh, P; Van Duppen, P; Venhart, M; Wakabayashi, Y; Wendt K D A

    2013-01-01

    The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of smallest quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical behaviour is the energy required to remove one electron from the valence shell, referred to as the ionization potential. Here we use laser spectroscopy to probe the optical spectrum of astatine near the ionization threshold. The observed series of Rydberg states enabled the first determination of the ionization potential of the astatine atom, 9.317510(8) eV. New ab initio calculations were performed to support the experimental result. The measured value serves as a benchmark for quantum chemistry calculations of the properties of astatine as well as for the theoretical prediction of the ionization potential of super-heavy element 117, the heaviest homologue of astatine.

  9. Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates.

    Science.gov (United States)

    Aneheim, Emma; Gustafsson, Anna; Albertsson, Per; Bäck, Tom; Jensen, Holger; Palm, Stig; Svedhem, Sofia; Lindegren, Sture

    2016-03-16

    Effective treatment of metastasis is a great challenge in the treatment of different types of cancers. Targeted alpha therapy utilizes the short tissue range (50-100 μm) of α particles, making the method suitable for treatment of disseminated occult cancers in the form of microtumors or even single cancer cells. A promising radioactive nuclide for this type of therapy is astatine-211. Astatine-211 attached to tumor-specific antibodies as carrier molecules is a system currently under investigation for use in targeted alpha therapy. In the common radiolabeling procedure, astatine is coupled to the antibody arbitrarily on lysine residues. By instead coupling astatine to disulfide bridges in the antibody structure, the immunoreactivity of the antibody conjugates could possibly be increased. Here, the disulfide-based conjugation was performed using a new coupling reagent, maleimidoethyl 3-(trimethylstannyl)benzamide (MSB), and evaluated for chemical stability in vitro. The immunoconjugates were subsequently astatinated, resulting in both high radiochemical yield and high specific activity. The MSB-conjugate was shown to be stable with a long shelf life prior to the astatination. In a comparison of the in vivo distribution of the new immunoconjugate with other tin-based immunoconjugates in tumor-bearing mice, the MSB conjugation method was found to be a viable option for successful astatine labeling of different monoclonal antibodies. PMID:26791409

  10. Measurement of the first ionization potential of astatine by laser ionization spectroscopy

    OpenAIRE

    Rothe, S.; A. N. Andreyev; Antalic, S; Borschevsky, A.; Capponi, L.; Cocolios, T.E.; Witte, H.; Eliav, E.; Fedorov, D. V.; Fedosseev, V. N.; Fink, D. A.; Fritzsche, S.; Ghys, L.; Huyse, M.; Imai, N.

    2013-01-01

    The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of the minute quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical behaviour is the energy required to remove one electron from the valence shell, referred to as the ionization potential. Here we use laser spectroscopy to probe the optical spectrum of astatine near the io...

  11. Automated astatination of biomolecules - a stepping stone towards multicenter clinical trials

    DEFF Research Database (Denmark)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom;

    2015-01-01

    To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical...... and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting...... vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method...

  12. Study of Astatine (III) reactions with O, S and N ligands in solution

    International Nuclear Information System (INIS)

    Full text of publication follows. Astatine (At, Z=85: [Xe]4f145d106s26p5) belongs to the halogen group and is located below iodine in the periodic table. One of its isotopes (211At) appears promising as a therapeutic agent in nuclear medicine (Ref.1) owing to the energy of the alpha particles emitted during the disintegration of its nucleus and its short physical half-life (7.2 h). Since there are no stable isotopes of astatine, the chemistry of this element remains poorly understood. Generally, At is supposed to behave as a halogen (Ref.2) but it has been shown recently in our group that astatine presents a metallic behaviour in aqueous solution: it notably exists as At+ and AtO+ species under the oxidation states +I and +III (Ref.3). At the present time, the number of studies dealing with the complexation properties of the cationic forms of astatine remains limited (Ref.4), owing to its low availability. In this work, we have investigated the reactions of AtO+ species with different hetero-atomic (N, S, O) model ligands. A combined approach based on experimental and theoretical studies has been used (Ref.5). On account of the difficulties of experimental investigations of astatine species, the reactivity of AtO+ was explored using a competition method founded on astatine distributions between two distinct phases. Furthermore, for each AtO+/ ligand complex, the nature of the species formed and the associated thermodynamic constants were determined by computational modeling (DFT calculations). In this framework, an original computational methodology was developed to take into account the specificities of astatine, notably the associated relativistic effects. The computed equilibrium constants have been confronted with the experimental results. This comparison demonstrates an outstanding coherence between experience and theory. Furthermore, the analysis of the results shows a key role of solvent effects on astatine chemistry. Lastly, a specific reactivity for the

  13. Some aspects of the organic, biological and inorganic chemistry of astatine

    International Nuclear Information System (INIS)

    Astatine has no stable isotopes and the radioactive isotopes with half-lives sufficiently long for chemical experiments (209At, 210At, 211At) must be produced artificially with a cyclotron or with a high energy accelerator by spallation of Th. This thesis deals with the synthesis and chemistry of At-compounds and the determination of some of their properties. (C.F.)

  14. Astatine-211 Pathway from Radiochemistry to Clinical Investigation

    International Nuclear Information System (INIS)

    Particularly in clinical settings where tumour burden is low and cancers are located in close proximity to essential normal tissue structures, α-particle emitting radionuclides can offer significant advantages for targeted radionuclide therapy. One of the first alpha emitters to be evaluated for this purpose is the 7.2-h half-life radiohalogen Astatine-211 (211At). From a commercialization-potential perspective 211At, is less appealing than the longer half-life alpha particle emitters Radium-223, Actinium-225 and Thorium-227, which have become the focus of many laboratories. However, if methods for providing a better supply of 211At could be developed, this alpha emitter would be the radionuclide of choice for many potential therapeutic applications. With regard to the production of 211At, this can be readily be accomplished by bombarding natural bismuth targets with 28−29.5 MeV alpha particles via the 209Bi(α,2n)211At reaction. The goal is to utilize an alpha particle beam energy that provides the required balance for maximizing 211At production while minimizing creation of 210At, which is problematic because of its 138.4-day half life alpha-particle emitting daughter, 210Po. For most intended clinical applications, alpha particle beam energy of about 29 MeV offers the best compromise between maximizing yield and providing 211At with sufficient radionuclidic purity for clinical use. Clinically relevant levels of 211At have been produced at several institutions using both internal and external cyclotron targets

  15. An attempt to explore the production routes of Astatine radionuclides: Theoretical approach

    OpenAIRE

    Maiti, Moumita; Lahiri, Susanta

    2008-01-01

    In order to fulfil the recent thrust of Astatine radionuclides in the field of nuclear medicine various production routes have been explored in the present work. The possible production routes of $^{209-211}$At comprise both light and heavy ion induced reactions at the bombarding energy range starting from threshold to maximum 100 MeV energy. For this purpose, we have used the nuclear reaction model codes TALYS, ALICE91 and PACE-II. Excitation functions of those radionuclides, produced throug...

  16. Determination of the electron affinity of astatine and polonium by laser photodetachment

    CERN Multimedia

    We propose to conduct the first electron anity (EA) measurements of the two elements astatine (At) and polonium (Po). Collinear photodetachment spectroscopy will allow us to measure these quantities with an uncertainty limited only by the spectral linewidth of the laser. We plan to use negative ion beams of the two radioactive elements At and Po, which are only accessible on-line and at ISOLDE. The feasibility of our proposed method and the functionality of the experimental setup have been demonstrated at ISOLDE in o-line tests by the clear observation of the photodetachment threshold for stable iodine. This proposal is based on our Letter of Intent I-148 [1].

  17. Unexpected Behavior of the Heaviest Halogen Astatine in the Nucleophilic Substitution of Aryliodonium Salts.

    Science.gov (United States)

    Guérard, François; Lee, Yong-Sok; Baidoo, Kwamena; Gestin, Jean-François; Brechbiel, Martin W

    2016-08-22

    Aryliodonium salts have become precursors of choice for the synthesis of (18) F-labeled tracers for nuclear imaging. However, little is known on the reactivity of these compounds with heavy halides, that is, radioiodide and astatide, at the radiotracer scale. In the first comparative study of radiohalogenation of aryliodonium salts with (125) I(-) and (211) At(-) , initial experiments on a model compound highlight the higher reactivity of astatide compared to iodide, which could not be anticipated from the trends previously observed within the halogen series. Kinetic studies indicate a significant difference in activation energy (Ea =23.5 and 17.1 kcal mol(-1) with (125) I(-) and (211) At(-) , respectively). Quantum chemical calculations suggest that astatination occurs via the monomeric form of an iodonium complex whereas iodination occurs via a heterodimeric iodonium intermediate. The good to excellent regioselectivity of halogenation and high yields achieved with diversely substituted aryliodonium salts indicate that this class of compounds is a promising alternative to the stannane chemistry currently used for heavy radiohalogen labeling of tracers in nuclear medicine. PMID:27305065

  18. Part I: $\\beta$-delayed fission, laser spectroscopy and shape-coexistence studies with astatine beams; Part II: Delineating the island of deformation in the light gold isotopes by means of laser spectroscopy

    CERN Document Server

    Andreyev, Andrei

    2013-01-01

    Part I: $\\beta$-delayed fission, laser spectroscopy and shape-coexistence studies with astatine beams; Part II: Delineating the island of deformation in the light gold isotopes by means of laser spectroscopy

  19. ASTATINE-211 RADIOCHEMISTRY: THE DEVELOPMENT OF METHODOLOGIES FOR HIGH ACTIVITY LEVEL RADIOSYNTHESIS

    Energy Technology Data Exchange (ETDEWEB)

    MICHAEL R. ZALUTSKY

    2012-08-08

    Targeted radionuclide therapy is emerging as a viable approach for cancer treatment because of its potential for delivering curative doses of radiation to malignant cell populations while sparing normal tissues. Alpha particles such as those emitted by 211At are particularly attractive for this purpose because of their short path length in tissue and high energy, making them highly effective in killing cancer cells. The current impact of targeted radiotherapy in the clinical domain remains limited despite the fact that in many cases, potentially useful molecular targets and labeled compounds have already been identified. Unfortunately, putting these concepts into practice has been impeded by limitations in radiochemistry methodologies. A critical problem is that the synthesis of therapeutic radiopharmaceuticals provides additional challenges in comparison to diagnostic reagents because of the need to perform radio-synthesis at high levels of radioactivity. This is particularly important for {alpha}-particle emitters such as 211At because they deposit large amounts of energy in a highly focal manner. The overall objective of this project is to develop convenient and reproducible radiochemical methodologies for the radiohalogenation of molecules with the {alpha}-particle emitter 211At at the radioactivity levels needed for clinical studies. Our goal is to address two problems in astatine radiochemistry: First, a well known characteristic of 211At chemistry is that yields for electrophilic astatination reactions decline as the time interval after radionuclide isolation from the cyclotron target increases. This is a critical problem that must be addressed if cyclotrons are to be able to efficiently supply 211At to remote users. And second, when the preparation of high levels of 211At-labeled compounds is attempted, the radiochemical yields can be considerably lower than those encountered at tracer dose. For these reasons, clinical evaluation of promising 211At

  20. An all-solid state laser system for the laser ion sources RILIS and in-source laser spectroscopy of astatine at ISOLDE/CERN

    Energy Technology Data Exchange (ETDEWEB)

    Rothe, Sebastian

    2012-09-24

    This doctoral thesis describes the extension of the resonance ionization laser ion source RILIS at CERN/ISOLDE by the addition of an all-solid state tunable titanium:sapphire (Ti:Sa) laser system to complement the well-established system of dye lasers. Synchronous operation of the so called Dual RILIS system of Ti:Sa and dye lasers was investigated and the potential for increased ion beam intensity, reliability, and reduced setup time has been demonstrated. In-source resonance ionization spectroscopy was performed at ISOLDE/CERN and at ISAC/TRIUMF radioactive ion beam facilities to develop an efficient and selective three-colour ionization scheme for the purely radioactive element astatine. A LabVIEW based monitoring, control and measurement system was conceived which enabled, in conjunction with Dual RILIS operation, the spectroscopy of high lying Rydberg states, from which the ionization potential of the astatine atom was determined for the first time experimentally.

  1. An all-solid state laser system for the laser ion sources RILIS and in-source laser spectroscopy of astatine at ISOLDE/CERN

    International Nuclear Information System (INIS)

    This doctoral thesis describes the extension of the resonance ionization laser ion source RILIS at CERN/ISOLDE by the addition of an all-solid state tunable titanium:sapphire (Ti:Sa) laser system to complement the well-established system of dye lasers. Synchronous operation of the so called Dual RILIS system of Ti:Sa and dye lasers was investigated and the potential for increased ion beam intensity, reliability, and reduced setup time has been demonstrated. In-source resonance ionization spectroscopy was performed at ISOLDE/CERN and at ISAC/TRIUMF radioactive ion beam facilities to develop an efficient and selective three-colour ionization scheme for the purely radioactive element astatine. A LabVIEW based monitoring, control and measurement system was conceived which enabled, in conjunction with Dual RILIS operation, the spectroscopy of high lying Rydberg states, from which the ionization potential of the astatine atom was determined for the first time experimentally.

  2. Radiobiological Effects of Alpha-Particles from Astatine-211: From DNA Damage to Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Claesson, Kristina

    2011-05-15

    In recent years, the use of high linear energy transfer (LET) radiation for radiotherapeutic applications has gained increased interest. Astatine-211 (211At) is an alpha-particle emitting radionuclide, promising for targeted radioimmunotherapy of isolated tumor cells and microscopic clusters. To improve development of safe radiotherapy using 211At it is important to increase our knowledge of the radiobiological effects in cells. During radiotherapy, both tumors and adjacent normal tissue will be irradiated and therefore, it is of importance to understand differences in the radio response between proliferating and resting cells. The aim of this thesis was to investigate effects in fibroblasts with different proliferation status after irradiation with alpha-particles from 211At or X-rays, from inflicted DNA damage, to cellular responses and biological consequences. Throughout this work, irradiation was performed with alpha-particles from 211A or X-rays. The induction and repair of double-strand breaks (DSBs) in human normal fibroblasts were investigated using pulsed-field gel electrophoresis and fragment analysis. The relative biological effectiveness (RBE) of 211At for DSB induction varied between 1.4 and 3.1. A small increase of DSBs was observed in cycling cells compared to stationary cells. The repair kinetics was slower after 211At and more residual damage was found after 24 h. Comparison between cells with different proliferation status showed that the repair was inefficient in cycling cells with more residual damage, regardless of radiation quality. Activation of cell cycle arrests was investigated using immunofluorescent labeling of the checkpoint kinase Chk2 and by measuring cell cycle distributions with flow cytometry analysis. After alpha-particle irradiation, the average number of Chk2-foci was larger and the cells had a more affected cell cycle progression for several weeks compared with X-irradiated cells, indicating a more powerful arrest after 211At

  3. Final Report for research grant "Development of Methods for High Specific Activity Labeling of Biomolecules Using Astatine-211 in Different Oxidation States"

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, D., Scott

    2011-12-14

    The overall objective of this research effort was to develop methods for labeling biomolecules with higher oxidation state species of At-211. This was to be done in an effort to develop reagents that had higher in vivo stability than the present carbon-bonded At-211-labeled compounds. We were unsuccessful in that effort, as none of the approaches studied provided reagents that were stable to in vivo deastatination. However, we gained a lot of information about At-211 in higher oxidation states. The studies proved to be very difficult as small changes in pH and other conditions appeared to change the nature of the species that obtained (by HPLC retention time analyses), with many of the species being unidentifiable. The fact that there are no stable isotopes of astatine, and the chemistry of the nearest halogen iodine is quite different, made it very difficult to interpret results of some experiments. With that said, we believe that a lot of valuable information was obtained from the studies. The research effort evaluated: (1) methods for chemical oxidation of At-211, (2) approaches to chelation of oxidized At-211, and (3) approaches to oxidation of astatophenyl compounds. A major hurdle that had to be surmounted to conduct the research was the development of HPLC conditions to separate and identify the various oxidized species formed. Attempts to develop conditions for separation of iodine and astatine species by normal and reversed-phase TLC and ITLC were not successful. However, we were successful in developing conditions (from a large number of attempts) to separate oxidized forms of iodine ([I-125]iodide, [I-125]iodate and [I-125]periodate) and astatine ([At-211]astatide, [At-211]astatate, [At-211]perastatate, and several unidentified At-211 species). Information on the basic oxidation and characterization of At-211 species is provided under Objective 1. Conditions were developed to obtain new At-211 labeling method where At-211 is chelated with the DOTA and

  4. Evaluation of a Wet Chemistry Method for Isolation of Cyclotron Produced [211At]Astatine

    Directory of Open Access Journals (Sweden)

    Shigeki Watanabe

    2013-09-01

    Full Text Available A “wet chemistry” approach for isolation of 211At from an irradiated bismuth target is described. The approach involves five steps: (1 dissolution of bismuth target in conc. HNO3; (2 removal of the HNO3 by distillation; (3 dissolution of residue in 8 M HCl; (4 extraction of 211At from 8 M HCl into DIPE; and (5 extraction of 211At from DIPE into NaOH. Results from 55 “optimized” 211At isolation runs gave recovery yields of approximately 78% after decay and attenuation corrections. An attenuation-corrected average of 26 ± 3 mCi in the target provided isolated (actual yields of 16 ± 3 mCi of 211At. A sixth step, used for purification of 211At from trace metals, was evaluated in seven runs. In those runs, isolated 211At was distilled under reductive conditions to provide an average 71 ± 8% recovery. RadioHPLC analyses of the isolated 211At solutions, both initial and after distillation, were obtained to examine the 211At species present. The primary species of 211At present was astatide, but astatate and unidentified species were also observed. Studies to determine the effect of bismuth attenuation on 211At were conducted to estimate an attenuation factor (~1.33 for adjustment of 211At readings in the bismuth target.

  5. Production of Astatine-211 at the Duke University Medical Center for its regional distribution

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, Michael [Duke University Medical Center, Durham, NC (United States)

    2016-01-01

    Systemic targeted radiation therapy and radioimmunotherapy continue to be important tools in the treatment of certain cancers. Because of their high energy and short path length, alpha particle emitters such as 211At are more effective than either external beam x- ray or in vivo beta radiation in delivering potentially curative doses of radiation. The limited clinical trials that have been conducted to date have yielded encouraging responses in some patients, e.g., malignant brain tumors. In order to escalate the additional necessary research and development in radiochemistry, radiobiology and efficacy evaluation of alpha particle radiotherapeutics, it is universally agreed that access to an affordable, reliable supply of 211At is warranted. In conjunction with the Department of Energy's intent to enhance stable and radioactive isotope availability for research applications, it is the primary objective of this project to improve 211At production and purification capabilities at Duke so that this radionuclide can be supplied to researchers at other institutions throughout the US.The most widely used 211At production method involves the α,2n reaction on Bismuth using a cyclotron with beams ≤ 28 MeV. Yields can be enhanced with use of an internal target that allows for a higher alpha fluence plus efficient heat dissipation in the target. Both of these items are in place at Duke; however, in order to support production for multi-institutional use, irradiation campaigns in excess of 50 µAp and four hours duration will be needed. Further, post-irradiation processing equipment is lacking that will enable the distribution process. Financial support is sought for i) a shielded, ventilated processing/containment hood; ii) development of a post-irradiation target retrieval system; iii) fabrication of a 211At distillation and recovery module and iv) a performance review and, where needed, an enhancement of seven major subsystems that comprise the CS-30 Cyclotron. With these modifications in place, routine production of ≥200 mCi of At-211 should be readily achievable, given our methodological development of At-211 target preparation, internal target irradiation and dry distillation to recover the radionuclide.

  6. Final Report for grant entitled "Production of Astatine-211 for U.S. Investigators"

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, Daniel Scott

    2012-12-12

    Alpha-particle emitting radionuclides hold great promise in the therapy of cancer, but few alpha-emitters are available to investigators to evaluate. Of the alpha-emitters that have properties amenable for use in humans, 211At is of particular interest as it does not have alpha-emitting daughter radionuclides. Thus, there is a high interest in having a source of 211At for sale to investigators in the US. Production of 211At is accomplished on a cyclotron using an alpha-particle beam irradiation of bismuth metal. Unfortunately, there are few cyclotrons available that can produce an alpha particle beam for that production. The University of Washington has a cyclotron, one of three in the U.S., that is currently producing 211At. In the proposed studies, the things necessary for production and shipment of 211At to other investigators will be put into place at UW. Of major importance is the efficient production and isolation of 211At in a form that can be readily used by other investigators. In the studies, production of 211At on the UW cyclotron will be optimized by determining the best beam energy and the highest beam current to maximize 211At production. As it would be very difficult for most investigators to isolate the 211At from the irradiated target, the 211At-isolation process will be optimized and automated to more safely and efficiently obtain the 211At for shipment. Additional tasks to make the 211At available for distribution include obtaining appropriate shipping vials and containers, putting into place the requisite standard operating procedures for Radiation Safety compliance at the levels of 211At activity to be produced / shipped, and working with the Department of Energy, Isotope Development and Production for Research and Applications Program, to take orders, make shipments and be reimbursed for costs of production and shipment.

  7. An all-solid state laser system for the laser ion source RILIS and in-source laser spectroscopy of astatine at ISOLDE,CERN

    OpenAIRE

    Rothe, Sebastian

    2012-01-01

    This doctoral thesis describes the extension of the resonance ionization laser ion source RILIS at CERN/ISOLDE by the addition of an all-solid state tunable titanium:sapphire (Ti:Sa) laser system to complement the well-established system of dye lasers. Synchronous operation of the so called Dual RILIS system of Ti:Sa and dye lasers was investigated and the potential for increased ion beam intensity, reliability, and reduced setup time has been demonstrated. In-source resonance ionization spec...

  8. Compound list: simvastatin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available simvastatin SST 00117 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/simv...astatin.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/simv...astatin.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/simv...archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/simvastatin.Rat.in_vivo.Liver.Repeat.zip ...

  9. SPECT assay of radiolabeled monoclonal antibodies. Final performance report, March 1992--November 1995

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1995-12-01

    Research is described in the following areas: development and evaluation quantitatively of reconstruction algorithms with improved compensations for attenuation, scatter, and geometric collimator response; evaluation of single photon emission computed tomography (SPECT) quantification of iodine 123 and astatine 211; and the development and evaluation of SPECT pinhole imaging for low and medium energy photons.

  10. Shelf-life of ɛ-lysyl-3-(trimethylstannyl)benzamide immunoconjugates, precursors for 211At labeling of antibodies

    DEFF Research Database (Denmark)

    Aneheim, Emma; Halleröd, Jenny; Albertsson, Per;

    2015-01-01

    Astatine-211 is possibly the most promising radionuclide for targeted α-particle therapy when it comes to the treatment of occult disseminated cancer. Preclinical research has proven effective, and patient studies have been initiated based on these results. However, a lack of production capacity...

  11. 10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

    Science.gov (United States)

    2010-01-01

    .... Actinium Ac 89 Aluminum Al 13 Americium Am 95 Antimony Sb 51 Argon Ar 18 Arsenic As 33 Astatine At 85... Curium Cm 96 Dysprosium Dy 66 Einsteinium Es 99 Erbium Er 68 Europium Eu 63 Fermium Fm 100 Fluorine F...

  12. SPECT assay of radiolabeled monoclonal antibodies. Final performance report, March 1992--November 1995

    International Nuclear Information System (INIS)

    Research is described in the following areas: development and evaluation quantitatively of reconstruction algorithms with improved compensations for attenuation, scatter, and geometric collimator response; evaluation of single photon emission computed tomography (SPECT) quantification of iodine 123 and astatine 211; and the development and evaluation of SPECT pinhole imaging for low and medium energy photons

  13. Hurdles for a Broader Use of 211At and for the Synthesis of 211At-Labelled Radiopharmaceuticals at High Activities for Clinical Use

    International Nuclear Information System (INIS)

    One of the key impediments to the use of 211At is the very well known deleterious effect of high radiation fields caused by its alpha particles on the synthesis of 211At-labelled radiopharmaceuticals. This is problematic because radiolysis-mediated effects can produce diminishing efficiency of electrophilic astatination reactions due to increasing deposition of radiation dose with increasing activities and with the passage of the time. Astatine-211 has chemical properties that permit complex labelling strategies and a longer half-life than 213Bi that makes it more suitable when the targeting molecule does not gain immediate access to the tumour cells. The first clinical evaluation was published in 2001 [2] in patients with brain tumour. Although this study circumvents many of the challenges to entering clinical studies with 211At and many obstacles had to be surmounted before clinical studies could be initiated, several problems were encountered in maintaining efficient labelling with escalating radiation dose of α-particle even with fresh 211At elution [3]. Astatine-211 also has an additional hurdle to overcome before to its clinical application in labelled radiopharmaceuticals related with its production and distribution. Among the potential group of promising α- emitter it is the only one produced by cyclotrons, but due to the scarcity of cyclotrons equipped with 25−30 MeV α-particle beams, it will of necessity be utilized in distant locations from the site of production. It presents a major chemical challenge because the diminishing efficiency of electrophilic astatination reactions with the passage of the time is well known, a problem likely related to the radiolysis produced by the high LET (linear energy transfer) meaning that large amounts of energy are deposited in a highly localized manner. This problem has been most comprehensively investigated to understand and evaluate the role of the radiolysis effects of astatine alpha particles in the synthesis

  14. $\\beta$-delayed fission, laser spectroscopy and shape-coexistence studies with radioactive At beams

    CERN Multimedia

    We propose to study the $\\beta$-delayed fission, laser spectroscopy and radioactive decay of the newly available pure beams of neutron-deficient and neutron-rich astatine (Z=85) isotopes. The fission probability and the fission fragment distribution of the even-even isotopes $^{194,196}$Po following the $\\beta$-decay of the isotopes $^{194,196}$At will be studied with the Windmill setup. In-source laser spectroscopy will be performed on the entire astatine isotopic chain, using a combination of the Windmill setup, ISOLTRAP MR-ToF and ISOLDE Faraday. Radioactive decay data will be acquired at the Windmill setup throughout those studies and contribute to the global understanding of the phenomenon of shape coexistence in the neutron-deficient lead region.

  15. Production cross section of At radionuclides from $^{7}$Li+$^{\\textrm{nat}}$Pb and $^{9}$Be+$^{\\textrm{nat}}$Tl reactions

    CERN Document Server

    Maiti, Moumita

    2011-01-01

    Earlier we reported theoretical studies on the probable production of astatine radionuclides from $^{6,7}$Li and $^{9}$Be-induced reactions on natural lead and thalliun targets, respectively. For the first time, in this report, production of astatine radionuclides has been investigated experimentally with two heavy ion induced reactions: $^{9}$Be+$^{\\textrm{nat}}$Tl and $^{7}$Li+$^{\\textrm{nat}}$Pb. Formation cross sections of the evaporation residues, $^{207,208,209,210}$At, produced in (HI, xn) channel, have been measured by the stacked-foil technique followed by the off-line $\\gamma$-spectrometry at the low incident energies ($<$50 MeV). Measured excitation functions have been explained in terms of compound nuclear reaction mechanism using Weisskopf-Ewing and Hauser-Feshbach model. Absolute cross section values are lower than the respective theoretical predictions.

  16. Radiopharmaceutical Chemistry of Targeted Radiopharmaceutics. Synthesis of 211At-Labeled Radiopharmaceuticals at High Activities for Clinical Use

    International Nuclear Information System (INIS)

    Targeted α-particle radiotherapy is an appealing approach to cancer treatment because of the potential for delivering curative doses of radiation to tumor with minimal damage to normal tissue due to a range equivalent to only a few cell diameters. Compared with β-emitters they have significant advantages from a radiobiological perspective. The LET of 211At α-particles is more than 400 times higher than the β-particles emitted by 90Y, in addition the distance between ionizing events is almost the same as that between the two strands of DNA, yielding a high probability of creating non-repairable DNA damage. It gives the ability to kill cancer cells not compromised by hypoxia, dose rate effects or cell cycle position, enhancing their attractiveness for targeted radiotherapy. However, translation of the concept to the clinic has been slow, many obstacles had to be surmounted before clinical studies could be initiated, the first clinical evaluation of a 211At- labeled mAb was made in 2001. This study circumvents many of the challenges to entering clinical studies with 211At. But several problems were encountered in maintaining efficient labeling with escalating radiation dose of alpha-particle likely related to radiolysis. The impact of the radiolysis produced by the α-particle over the labeling chemistry is much higher in comparison with typical β-emitters due to a deposition of energy in the solvent in a highly localized manner two orders of magnitude per unit volume higher than 90Y or 131I. Due to these difficulties a comprehensive basic science study about the radiolytic effects of astatine alpha-particles over the synthesis of 211At-labeled radiopharmaceuticals was carried out. Its main goal was overcoming the problem of the synthesis of 211At-labeled radiopharmaceuticals at the high activities necessaries for therapy and also to extend the shelf life of astatine elutions. Briefly this study held several steps, the first one was to study the role of solvent

  17. Inclusive measurement of (p,πsup(-)xn) double charge exchange reactions on bismuth from threshold to 800 MeV

    International Nuclear Information System (INIS)

    The energy dependence of the total angle-integrated cross section for the production of astatine isotopes from (p,πsup(-)xn) double charge exchange reactions on bismuth (sup(209)Bi) was measured from 120 to 800 MeV using activation and radiochemical techniques. Chemical yields were estimated by direct radioassaying of sup(211)At activity in thin (approximately 1 mg/cmsup(2)), irradiated bismuth targets. Calculations of the contributions of secondary (2-step) reactions to these measured astatine yields were performed, based partially upon the observed sup(211)At activity although even at the highest energies, the contribution to products lighter than sup(207)At was negligible. These data for products with as many as 7 neutrons removed from the doubly coherent product (sup(210)At) display nearby gaussian shapes for the mass distributions of the astatine residues with the maximum occurring for about sup(204)At. The most probable momentum transfer deduced from these distributions for the initial πsup(-) production step was 335 MeV/c. The observed excitation functions display a behaviour similar to that observed for the yield of sup(210)Po from a (p,πsup(O)) reaction on sup(209)Bi, but radically different from that observed for inclusive πsup(-) reactions on a heavy nucleus. These data are discussed in terms of recent theoretical approaches to negative pion production from bismuth. In addition, a simple, schematic model is developed to treat the rapidly decreasing percentage of the total inclusive πsup(-) emission which is observed for this double charge exchange reaction. This model reflects the capacity of a nucleus to a source of internal energetic protons

  18. Human radiation studies: Remembering the early years: Oral history of Dr. Patricia Wallace Durbin, Ph.D., conducted November 11, 1994

    International Nuclear Information System (INIS)

    This report is a transcript of an interview of Dr. Patricia Wallace Durbin by representatives of the US DOE Office of Human Radiation Research. Dr. Durbin was selected for this interview because of her knowledge of the human plutonium injections and her recollections of key figures, especially Joseph Hamilton. After a brief biographical sketch Dr. Durbin discusses her loss of research funding from DOE, her recollections concerning research into strontium metabolism as part of Project Sunshine, her recollections relating to the rationale for studies of human metabolism of radionuclides, her remembrances of Dr. Hamilton's Astatine and Plutonium research, and her experiences in gathering archival records concerning these researches

  19. EFFECT OF MECHANICAL PROPERTIES OF MARTENSITE AND LOADING RATE ON DUAL PHASE STEELS

    OpenAIRE

    BAYRAM, Ali

    1998-01-01

    In this study, steel sheet materials were used in order to obtain dual-phase steel. Specimens for this purpose have been annealed in ferrite + astatine regions at the temperatures of 740, 760, 800 and 820 °C. The specimens were annealed at the different temperatures with corresponding times 20, 40 and 60 minutes and quenched into water. As a result of this dual-phase steels at different ferrite + martensite ratio were produced. Sheet specimens were tested at the range of loading rates of 1...

  20. Alpha-decay studies of the new isotopes sup 1 sup 9 sup 1 At and sup 1 sup 9 sup 3 At

    CERN Document Server

    Kettunen, H; Grahn, T; Greenlees, P T; Jones, P; Julin, R; Juutinen, S; Keenan, A; Kuusiniemi, P; Leino, M; Leppaenen, A P; Nieminen, P; Pakarinen, J; Rahkila, P; Uusitalo, J

    2003-01-01

    Detailed alpha-decay studies have been performed for the neutron-deficient isotopes sup 1 sup 9 sup 1 At and sup 1 sup 9 sup 3 At. The nuclei were produced in fusion-evaporation reactions of sup 5 sup 4 Fe and sup 5 sup 6 Fe ions with a sup 1 sup 4 sup 1 Pr target. The fusion products were separated in-flight using a gas-filled recoil separator and implanted into a position-sensitive silicon detector. The isotopes were identified using position, time and energy correlations between the implants and subsequent alpha-decays. Three alpha-decaying states were identified for sup 1 sup 9 sup 3 At and two for sup 1 sup 9 sup 1 At. The spin and parity of the initial states in the astatine isotopes were deduced based on unhindered alpha-decays to states in the bismuth daughter nuclei. In both astatine isotopes the 1/2 sup + intruder state was determined to be the ground state and a 7/2 sup - state to be the first-excited state. In sup 1 sup 9 sup 3 At the alpha-decay of the 13/2 sup + state was observed in coincidence...

  1. Rationalization of the solvation effects on the AtO+ ground-state change.

    Science.gov (United States)

    Ayed, Tahra; Réal, Florent; Montavon, Gilles; Galland, Nicolas

    2013-09-12

    (211)At radionuclide is of considerable interest as a radiotherapeutic agent for targeted alpha therapy in nuclear medicine, but major obstacles remain because the basic chemistry of astatine (At) is not well understood. The AtO(+) cationic form might be currently used for (211)At-labeling protocols in aqueous solution and has proved to readily react with inorganic/organic ligands. But AtO(+) reactivity must be hindered at first glance by spin restriction quantum rules: the ground state of the free cation has a dominant triplet character. Investigating AtO(+) clustered with an increasing number of water molecules and using various flavors of relativistic quantum methods, we found that AtO(+) adopts in solution a Kramers restricted closed-shell configuration resembling a scalar-relativistic singlet. The ground-state change was traced back to strong interactions, namely, attractive electrostatic interactions and charge transfer, with water molecules of the first solvation shell that lift up the degeneracy of the frontier π* molecular orbitals (MOs). This peculiarity brings an alternative explanation to the highly variable reproducibility reported for some astatine reactions: depending on the production protocols (with distillation in gas-phase or "wet chemistry" extraction), (211)At may or may not readily react. PMID:23944251

  2. New developments of the in-source spectroscopy method at RILIS/ISOLDE

    CERN Document Server

    Marsh, B A; Imai, N; Seliverstov, M D; Rothe, S; Sels, S; Capponi, L; Rossel, R E; Franchoo, S; Wendt, K; Focker, G J; Kalaninova, Z; Sjoedin, A M; Popescu, L; Nicol, T; Huyse, M; Radulov, D; Atanasov, D; Kesteloot, N; Borgmann, Ch; Cocolios, T E; Lecesne, N; Ghys, L; Pauwels, D; Rapisarda, E; Kreim, S; Liberati, V; Wolf, R N; Andel, B; Schweikhard, L; Lane, J; Derkx, X; Kudryavtsev, Yu; Zemlyanoy, S G; Fedosseev, V N; Lynch, K M; Rosenbusch, M; Van Duppen, P; Lunney, D; Manea, V; Barzakh, A E; Andreyev, A N; Truesdale, V; Flanagan, K T; Molkanov, P L; Koester, U; Van Beveren, C; Wienholtz, F; Goodacre, T Day; Antalic, S; Bastin, B; De Witte, H; Fink, D A; Fedorov, D V

    2013-01-01

    At the CERN ISOLDE facility, long isotope chains of many elements are produced by proton-induced reactions in target materials such as uranium carbide. The Resonance Ionization Laser Ion Source (RILIS) is an efficient and selective means of ionizing the reaction products to produce an ion beam of a chosen isotope. Coupling the RILIS with modern ion detection techniques enables highly sensitive studies of nuclear properties (spins, electromagnetic moments and charge radii) along an isotope chain, provided that the isotope shifts and hyperfine structure splitting of the atomic transitions can be resolved. At ISOLDE the campaign to measure the systematics of isotopes in the lead region (Pb, Bi, Tl and Po) has been extended to include the gold and astatine isotope chains. Several developments were specifically required for the feasibility of the most recent measurements: new ionization schemes (Po, At); a remote controlled narrow line-width mode of operation for the RILIS Ti:sapphire laser (At, Au, Po); isobar fr...

  3. Development of 211At Chemistry for Labelling Biomolecules

    International Nuclear Information System (INIS)

    Our studies have demonstrated that high recovery of 211At can be obtained using a “wet chemistry” approach to isolation from the bismuth target. We have also demonstrated that direct labelling of antibody-B10 conjugates with 211At can be performed in high yields, and that the astatinated antibodies are stable to in vivo deastatination. While these results will allow us to enter clinical studies with 211At-labelled antibodies, the chemistry associated with 211At is not fully understood. Therefore, it is important that many more basic studies to be conducted with 211At, so the optimal labelling reagent for each type of disease-targeting agent becomes apparent

  4. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    DEFF Research Database (Denmark)

    Lyckesvärd, Madeleine Nordén; Delle, Ulla; Kahu, Helena;

    2014-01-01

    Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same...... levels of γH2AX decreased during the first 24h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to (211)At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels...... cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative effectiveness of alpha particles....

  5. EFFECT OF MECHANICAL PROPERTIES OF MARTENSITE AND LOADING RATE ON DUAL PHASE STEELS

    Directory of Open Access Journals (Sweden)

    Ali BAYRAM

    1998-03-01

    Full Text Available In this study, steel sheet materials were used in order to obtain dual-phase steel. Specimens for this purpose have been annealed in ferrite + astatine regions at the temperatures of 740, 760, 800 and 820 °C. The specimens were annealed at the different temperatures with corresponding times 20, 40 and 60 minutes and quenched into water. As a result of this dual-phase steels at different ferrite + martensite ratio were produced. Sheet specimens were tested at the range of loading rates of 10, 50 and 259 mm/min. Strength properties of dual-phase steels were investigated depending on annealing temperature, ratio of martensite and loading rate.

  6. New developments of the in-source spectroscopy method at RILIS/ISOLDE

    Energy Technology Data Exchange (ETDEWEB)

    Marsh, B.A., E-mail: bruce.marsh@cern.ch [CERN, CH-1211 Geneva (Switzerland); Andel, B. [Comenius University, Bratislava (Slovakia); Andreyev, A.N. [University of York, Department of Physics, York YO10 5DD (United Kingdom); Antalic, S. [Comenius University, Bratislava (Slovakia); Atanasov, D. [Max-Planck-Institut für Kernphysik, Saupfercheckweg 1, 69117 Heidelberg (Germany); Barzakh, A.E. [Petersburg Nuclear Physics Institute, NRC Kurchatov Institute, 188300 Gatchina (Russian Federation); Bastin, B. [Grand Accérateur National d’Ions Lourds (GANIL), Bd Henri Becquerel, F-14076 Caen (France); Borgmann, Ch. [Max-Planck-Institut für Kernphysik, Saupfercheckweg 1, 69117 Heidelberg (Germany); Capponi, L. [KU Leuven, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Cocolios, T.E.; Day Goodacre, T. [CERN, CH-1211 Geneva (Switzerland); University of Manchester, Manchester (United Kingdom); Dehairs, M. [KU Leuven, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Derkx, X. [University of the West of Scotland, School of Engineering, Paisley PA1 2BE (United Kingdom); De Witte, H. [KU Leuven, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Fedorov, D.V. [Petersburg Nuclear Physics Institute, NRC Kurchatov Institute, 188300 Gatchina (Russian Federation); Fedosseev, V.N.; Focker, G.J. [CERN, CH-1211 Geneva (Switzerland); Fink, D.A. [Ruprecht-Karls Universität, Seminarstr. 2, 69117 Heidelberg (Germany); CERN, CH-1211 Geneva (Switzerland); Flanagan, K.T. [University of Manchester, Manchester (United Kingdom); Franchoo, S. [CSNSM-IN2P3-CNRS, Université Paris-Sud, 91406 Orsay (France); and others

    2013-12-15

    Highlights: • Upgrade of the lasers, detectors and data acquisition for in-source resonance ionization spectroscopy at ISOLDE. • First use of the ISOLTRAP MR-ToF MS in combination with laser spectroscopy at ISOLDE. • Resonance ionization of astatine for the study of its nuclear structure. -- Abstract: At the CERN ISOLDE facility, long isotope chains of many elements are produced by proton-induced reactions in target materials such as uranium carbide. The Resonance Ionization Laser Ion Source (RILIS) is an efficient and selective means of ionizing the reaction products to produce an ion beam of a chosen isotope. Coupling the RILIS with modern ion detection techniques enables highly sensitive studies of nuclear properties (spins, electromagnetic moments and charge radii) along an isotope chain, provided that the isotope shifts and hyperfine structure splitting of the atomic transitions can be resolved. At ISOLDE the campaign to measure the systematics of isotopes in the lead region (Pb, Bi, Tl and Po) has been extended to include the gold and astatine isotope chains. Several developments were specifically required for the feasibility of the most recent measurements: new ionization schemes (Po, At); a remote controlled narrow line-width mode of operation for the RILIS Ti:sapphire laser (At, Au, Po); isobar free ionization using the Laser Ion Source Trap, LIST (Po); isobar selective particle identification using the multi-reflection time-of-flight mass separator (MR-ToF MS) of ISOLTRAP (Au, At). These are summarized as part of an overview of the current status of the in-source resonance ionization spectroscopy setup at ISOLDE.

  7. Study of Neutron-Deficient $^{202-205}$Fr Isotopes with Collinear Resonance Ionization Spectroscopy

    CERN Document Server

    De Schepper, Stijn; Cocolios, Thomas; Budincevic, Ivan

    The scope of this master’s thesis is the study of neutron-deficient $^{202−205}$Fr isotopes. These isotopes are inside the neutron-deficient lead region, a region that has shown evidence of shape coexistence. For this thesis, this discussion is limited to the phenomenon where a low lying excited state has a different shape than the ground state. Shape coexistence is caused by intruder states. These are single-particle Shell Model states that are perturbed in energy due to the interaction with a deformed core. In the neutron-deficient lead region the main proton intruder orbit is the 3s$_{1/2}$orbit. When going towards more neutron-deficient isotopes, deformation increases. The $\\pi3s_{1/2}$orbit will rise in energy and will eventually become the ground state in odd- A bismuth (Z=83) isotopes. It is also observed in odd-A astatine (Z=85) isotopes, already in less neutron-deficient nuclei. The same phenomenon is expected to be present francium (Z=87) isotopes already at $^{199}$Fr. Although it is currently ...

  8. The biokinetics of alpha-particle emitting radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, D.M. [School of Chemistry, Cardiff Univ., Cardiff (United Kingdom); Duffield, J.R. [Faculty of Applied Sciences, Univ. of the West of England, Bristol (United Kingdom)

    2005-07-01

    The past two decades have seen wide interest in the application of alpha-particle emitting radionuclides for targeted endoradiotherapy and a large number of compounds labeled with {sup 211}At (T{sup 1}/{sub 2} 7.21 h), {sup 212}Bi (T{sup 1}/{sub 2} 1 h) or {sup 213}Bi (T{sup 1}/{sub 2} 0.78 h) have been studied. Knowledge of the biokinetic behaviour of such agents is important both for their optimal clinical exploitation and for general radiological protection purposes. Animal studies of the distribution and retention of {sup 211}At compounds, including ionic astatide, substituted aromatic compounds and labelled monoclonal antibodies, have provided new information on the biochemistry of astatine. With respect the thyroid gland the uptake of the astatide ion has been shown to be very much lower than that of the iodide ion. Less information is available for {sup 212}Bi-labelled radiopharmaceuticals. The available data for both {sup 211}At and {sup 212}Bi radiopharmaceuticals are reviewed. Cautious generic biokinetic models for inorganic and simple organic compounds of {sup 211}At and {sup 212}Bi; for [{sup 211}At]-, and [{sup 212}Bi]-biphosphonates and for [{sup 211}At]-, and [{sup 212}Bi]-monoclonal antibodies, are proposed for use in general radiological protection when compound-specific data are not available. (orig.)

  9. Combined effect of gefitinib ('Iressa', ZD1839) and targeted radiotherapy with {sup 211}At-EGF

    Energy Technology Data Exchange (ETDEWEB)

    Sundberg, Aasa Liljegren; Orlova, Anna; Gedda, Lars; Tolmachev, Vladimir; Carlsson, Joergen [Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala (Sweden); Almqvist, Ylva [Division of Radiology, Uppsala University, Uppsala (Sweden); Blomquist, Erik [Division of Oncology, Uppsala University, Uppsala (Sweden); Jensen, Holger J. [Department of Clinical Physiology and Nuclear Medicine, PET and Cyclotron Unit, Rigshospitalet, Copenhagen (Denmark)

    2003-10-01

    The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib ['Iressa' (trademark of the AstraZeneca group of companies), ZD1839] increases the cellular uptake of radiolabelled epidermal growth factor (EGF). We investigated gefitinib treatment combined with astatine-211 EGF targeting in vitro using two cell lines expressing high levels of EGFR: A431 (sensitive to gefitinib) and U343MGaCl2:1 (resistant to gefitinib). In both cell lines, the uptake of {sup 211}At-EGF was markedly increased by concomitant treatment with gefitinib. Survival was investigated using both a clonogenic survival assay and a cell growth assay. Combined gefitinib and {sup 211}At-EGF treatment reduced the survival of U343 cells 3.5-fold compared with {sup 211}At-EGF alone. In A431 cells, {sup 211}At-EGF treatment resulted in very low survival, but combined treatment with gefitinib increased the survival by about 20-fold. These results indicate that combined treatment with gefitinib might increase the effect of ligand-mediated radionuclide therapy in gefitinib-resistant tumours and decrease the effect of such therapy in gefitinib-sensitive tumours. (orig.)

  10. Alpha particle emitters in medicine

    International Nuclear Information System (INIS)

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 (211At) and natural bismuth-212 (212Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 (223Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs

  11. Tumor Immunotargeting Using Innovative Radionuclides

    Directory of Open Access Journals (Sweden)

    Françoise Kraeber-Bodéré

    2015-02-01

    Full Text Available This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

  12. Development of Reagents for Application of At-211 to Targeted Radionuclide Therapy of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, D. Scott

    2011-12-23

    This grant covered only a period of 4 months as the major portion of the award was returned to DOE due to an award of funding from NIH that covered the same research objectives. A letter regarding the termination of the research is attached as the last page of the Final Report. The research conducted was limited due to the short period of this grant, but the results obtained in that period are outlined in the Final Report. The studies addressed in the research effort were directed at a problem that is of critical importance to the in vivo application of the alpha-particle emitting radionuclide At-211. That problem, low in vivo stability of many astatinated molecules, severely limits the use of At-211 in therapeutic applications. The advances sought in the studies were expected to expand the types of biomolecules that can be used as carriers of At-211, and provide improved in vivo targeting of the radiation dose compared with the dose delivered to normal tissue.

  13. Tumor immunotargeting using innovative radionuclides.

    Science.gov (United States)

    Kraeber-Bodéré, Françoise; Rousseau, Caroline; Bodet-Milin, Caroline; Mathieu, Cédric; Guérard, François; Frampas, Eric; Carlier, Thomas; Chouin, Nicolas; Haddad, Ferid; Chatal, Jean-François; Faivre-Chauvet, Alain; Chérel, Michel; Barbet, Jacques

    2015-01-01

    This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality. PMID:25679452

  14. SPECT assay of radiolabeled monoclonal antibodies. Progress report, September 1, 1992--August 24, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1993-08-20

    The overall goal of this project is to improve the effectiveness of single photon emission computed tomography (SPECT) to image and quantify radiolabeled monoclonal antibodies. During the past year, we have made significant progress toward this goal, and this report summarizes that work. Our efforts have been mainly directed along three fronts. First, we have developed and tested new reconstruction methods including three-dimensional iterative algorithms that model non-uniform attenuation and distance-dependent detector response. Both fan beam and parallel beam collimator geometries have been modeled and novel ways of improving the efficiency of the computationally intensive methods have been introduced. Second, an ultra-high resolution, small field-of-view pinhole collimator has been constructed and evaluated. Reconstructed spatial resolution of 1 to 3 mm (FWHM) has been achieved in phantom scans with a useful field-of-view of 9 to 10 cm. Finally, we have investigated the ability of SPECT to image and quantify astatine-211 distributions. Reconstructed images of phantom data demonstrated quantitative accuracy to within 10% with proper attenuation and scatter compensation.

  15. Silver impregnated nanoparticles of titanium dioxide as carriers for {sup 211}At

    Energy Technology Data Exchange (ETDEWEB)

    Cedrowska, Edyta; Lyczko, Monika; Piotrowska, Agata; Bilewicz, Aleksander [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); Stolarz, Anna; Trcinska, Agnieszka [Warsaw Univ. (Poland). Heavy Ion Lab.; Szkliniarz, Katarzyna [Silesia Univ. Katowice (Poland). Inst. of Physics; Was, Bogdan [Polish Academy of Science, Cracow (Poland). Inst. of Nuclear Physics

    2016-08-01

    The {sup 211}At radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately use of {sup 211}At is limited, because astatine as the heaviest halogen forms weak bond with carbon atoms in the biomolecules which makes {sup 211}At bioconjugates unstable in physiological conditions. In our work we propose a new solution for binding of {sup 211}At which consists of using nanoparticles of titanium dioxide modified with silver atoms as carriers for {sup 211}At. Ag{sup +} cations have been absorbed on the nanometer-sized TiO{sub 2} particles (15 and 32 nm) through ion exchange process and were reduced in Tollens' reaction. The obtained TiO{sub 2}-Ag nanoparticles were labeled with {sup 211}At. It was found that labeling yields were almost quantitative under reducing conditions, while under oxidizing conditions they dropped to about 80%. The labeled nanoparticles exhibited very high stability in physiological salt, PBS buffer, solutions of peptides (0.001 M cysteine, 0.001 M glutathione) and in human blood serum. To make TiO{sub 2}/Ag nanoparticles well dispersed in water and biocompatible their surface was modified with a silane coupling agent containing poly(ethyleneglycol) molecules. The developed functionalization approach will allow us to attach biomolecules to the TiO{sub 2}/Ag surface.

  16. Nuclear and chemical data for life sciences

    International Nuclear Information System (INIS)

    Use of reactor produced radionuclides is popular in life sciences. However, cyclotron production of proton rich radionuclides are being more focused in recent times. These radionuclides have already gained attention in various fields, including life sciences, provided they are obtained in pure form. This article is a representative brief of our contributions in generating nuclear data for the production of proton rich radionuclides of terbium, astatine, technetium, ruthenium, cadmium, niobium, zirconium, rhenium, etc., which may have application in clinical, biological, agriculture studies or in basic research. The chemical data required to separate the product isotopes from the corresponding target matrix have been presented along with a few propositions of radiopharmaceuticals. It also emphasizes on the development of simple empirical technique, based on the nuclear reaction model analysis, to generate reliable nuclear data for the estimation of yield and angular distribution of emitted neutrons and light charged particles from light as well as heavy ion induced reactions on thick stopping targets. These data bear utmost important in radiation dosimetry. (author)

  17. Studies of Stable Octupole Deformations in the Radium Region

    CERN Multimedia

    2002-01-01

    The purpose of the present project is to locate and identify states in the atomic nuclei possessing stable pearshaped octupole deformation. Such states, formally related to the structures known in molecular physics, manifest themselves as families of parity doublets in odd nuclei.\\\\ \\\\ The best possibilities for observing stable octupole deformations are offered in the Ra-region. Both theoretical calculations and experimental indications support such expectations. Such indications are the non-observation of two-phonon octupole vibrational states in the ISOLDE studies of the even-even radium nuclei, and the reversed sign of the decoupling factor of the ground state band in |2|2|5Ra observed in the single-neutron transfer reactions. In order to establish the predicted strong E1 and E3-transitions between the parity doublets in odd nuclei with stable octupole deformations it is proposed to study conversion electrons in odd-mass francium radium and radon isotopes following the @b-decay of francium and astatine. \\...

  18. Alpha particle emitters in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.

    1989-09-01

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ({sup 211}At) and natural bismuth-212 ({sup 212}Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ({sup 223}Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs.

  19. Immuno-vectorization of radioelements emitters of alpha particles: a new therapy in cancerology

    International Nuclear Information System (INIS)

    The radio-immunotherapy is an anti cancerous therapy which consists in vectorising with immuno-specific agents very radio toxic radioelements on tumors or in their environment to destroy them. The first part of this report presents the different characteristics of antibodies as well as their means of production under monoclonal shapes specifically steered against a tumoral antigen of interest. The second part of this report replaces the importance of the immunological vectors in the context of the nuclear medicine. It is notably described that the different methods which allow to radio-label the vector, as well as the different ways of optimization which were envisaged to improve the targeting of radioelements on a tumor. These different developments allow to define the potential place of the alpha radio-immunotherapy in treatments and so re-place the interest of the experimental part. If the radio-immunotherapy, using beta emitters isotopes as the 131iodine or the90yttrium, is today current in anti cancerous therapy, it finds limits because of the disintegration characteristics of the isotopes it uses. Indeed, compared with alpha particles, the beta particles deposit less energy by unit of length in the crossed material.The experimental part of this report aims at studying the feasibility of the coupling between an immunological vector and an alpha emitter isotope.The different tests led on the bismuth 213, the bismuth 212, the lead 212 and the astatine 211 demonstrated that the fixation of these radionuclides was possible. This research theme is strengthened by the construction in Nantes of a cyclotron with high energy ( A.R.R.O.N.A.X.) and the optimization of the obtained promising results should allow a therapeutic use in oncology of the alpha radio-immunotherapy. (N.C.)

  20. Immuno-vectorization of radioelements emitters of alpha particles: a new therapy in cancerology; Immunovectorisation de radioelements emetteurs de particules alpha: une nouvelle voie therapeutique en cancerologie

    Energy Technology Data Exchange (ETDEWEB)

    Bourgeois, M

    2007-05-15

    The radio-immunotherapy is an anti cancerous therapy which consists in vectorising with immuno-specific agents very radio toxic radioelements on tumors or in their environment to destroy them. The first part of this report presents the different characteristics of antibodies as well as their means of production under monoclonal shapes specifically steered against a tumoral antigen of interest. The second part of this report replaces the importance of the immunological vectors in the context of the nuclear medicine. It is notably described that the different methods which allow to radio-label the vector, as well as the different ways of optimization which were envisaged to improve the targeting of radioelements on a tumor. These different developments allow to define the potential place of the alpha radio-immunotherapy in treatments and so re-place the interest of the experimental part. If the radio-immunotherapy, using beta emitters isotopes as the {sup 131}iodine or the{sup 90}yttrium, is today current in anti cancerous therapy, it finds limits because of the disintegration characteristics of the isotopes it uses. Indeed, compared with alpha particles, the beta particles deposit less energy by unit of length in the crossed material.The experimental part of this report aims at studying the feasibility of the coupling between an immunological vector and an alpha emitter isotope.The different tests led on the bismuth 213, the bismuth 212, the lead 212 and the astatine 211 demonstrated that the fixation of these radionuclides was possible. This research theme is strengthened by the construction in Nantes of a cyclotron with high energy ( A.R.R.O.N.A.X.) and the optimization of the obtained promising results should allow a therapeutic use in oncology of the alpha radio-immunotherapy. (N.C.)

  1. α-Imaging Confirmed Efficient Targeting of CD₄₅-Positive Cells After ²¹¹At-Radioimmunotherapy for Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Miller, Brian W.; Back, Tom; Santos, E. B.; Hamlin, Donald K.; Knoblaugh, E.; Frayo, Shani; Kenoyer, Aimee L.; Storb, Rainer; Press, O. W.; Wilbur, D. Scott; Pagel, John M.; Sandmaier, B. M.

    2015-09-03

    Alpha-radioimmunotherapy (α-RIT) targeting CD45 may substitute for total body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (MAb; CA12.10C12) protein dose for astatine-²¹¹(²¹¹At)-RIT, extending the analysis to include intra-organ ²¹¹At activity distribution and α-imaging-based small-scale dosimetry, along with imunohistochemical staining. Methods: Eight normal dogs were injected with either 0.75 (n=5) or 1.00 mg/kg (n=3) of ²¹¹At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 hours postinjection (p.i.), and six received autologous HCT three days after ²¹¹At-RIT, following lymph node and bone marrow biopsies at 2–4 and/or 19 hours p.i. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. ²¹¹At localization and small scale dosimetry were assessed using two α-imaging : α-camera and iQID. Results: Uptake of ²¹¹At was highest in spleen (0.31–0.61 %IA/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either MAb dose. Lymph nodes remained unsaturated, but displayed targeted ²¹¹At localization in T lymphocyte-rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.9, 3.0, and 4.2 Gy/210 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; 1 treated with 1.00 mg MAb/kg developed ascites and was euthanized 136 days after HCT. Conclusion: ²¹¹At-anti-CD45 RIT with 0.75 mg MAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient ²¹¹At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.

  2. Quantitative Single-Particle Digital Autoradiography with α-Particle Emitters for Targeted Radionuclide Therapy using the iQID Camera

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Brian W.; Frost, Sophia; Frayo, Shani; Kenoyer, Aimee L.; Santos, E. B.; Jones, Jon C.; Green, Damian J.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Orozco, Johnnie J.; Press, Oliver W.; Pagel, John M.; Sandmaier, B. M.

    2015-07-01

    Abstract Alpha emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50–80 μm) causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with alpha emitters may inactivate targeted cells with minimal radiation damage to surrounding tissues. For accurate dosimetry in alpha-RIT, tools are needed to visualize and quantify the radioactivity distribution and absorbed dose to targeted and non-targeted cells, especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, iQID (ionizing-radiation Quantum Imaging Detector), for use in alpha-RIT experiments. Methods: The iQID camera is a scintillator-based radiation detection technology that images and identifies charged-particle and gamma-ray/X-ray emissions spatially and temporally on an event-by-event basis. It employs recent advances in CCD/CMOS cameras and computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, we evaluated this system’s characteristics for alpha particle imaging including measurements of spatial resolution and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 (211At) activity distributions in cryosections of murine and canine tissue samples. Results: The highest spatial resolution was measured at ~20 μm full width at half maximum (FWHM) and the alpha particle background was measured at a rate of (2.6 ± 0.5) × 10–4 cpm/cm2 (40 mm diameter detector area). Simultaneous imaging of multiple tissue sections was performed using a large-area iQID configuration (ø 11.5 cm

  3. Clinical review on RIT

    International Nuclear Information System (INIS)

    disease stabilizations. Tumor uptake assessed by post-RIT immunoscintigraphy was a significant predictor of response. New beta emitters such as lutetium- 177, with better physical properties will further improve the safety of RIT and alpha emitters such as bismuth-213 or astatine-211 offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the setting of consolidation. Personalized dosimetry protocols, based in particular on quantitative PET imaging, should be developed to optimize injected activity. Within the scope of a 'theranostic' approach, pairs of beta+/beta- emitting radionuclides (124I/131I, 86Y/90Y, 64Cu/67Cu, 44Sc/47Sc) are very promising because the same distribution is expected both for imaging dosimetry and therapy with the same elements. (authors)

  4. Effects of Simvastatin on Ion Channel Currents in Ventricular Myocytes from Acute Infarcted Heart of Normocholesterolemic Rabbits

    Institute of Scientific and Technical Information of China (English)

    Chao Ding; Xianghua Fu; Li Yang; Huixiao Chen; Junxia Li; Yuying Zhao; Jie Li; Jie Wang

    2008-01-01

    Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rab-bit heart suffering from acute myocardial infarction (AMI), so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups: AMI group, simv-astatin intervention group (Statin group) and sham-operated control group (CON). Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg-1 · d-1 (Statin group) or placebo (AMI group) for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, inclu-ding sodium current (Ina), L-type calcium current (Ica-L) and transient outward potassium current (Ito). Results ① There was not significant difference in serum cholesterol concentration among three groups. ② The peak Ina current den-sity (at -30 mV) was significantly decreased in AMI group (-25.26±5. 28, n = 13), comparing with CON (-42. 78±5.48, n = 16), P < 0. 05, while it was significantly increased in Statin group (-39. 83±5. 65 pA/pF, n = 12) comparing with AMI group, P <0. 01; The peak I Ca-L current density (at 0 mV) was significantly decreased in AMI group (- 3.43±0. 92 pA/pF, n = 13) comparing with CON (- 4. 56±1.01 pA/pF, n = 15), P < 0. 05, while it was significantly increased in Statin group (-4. 18±0. 96 pA/pF, n = 12) comparing with AMI group, P <0. 05; The Ito current density (at + 60 mV) was significantly decreased in AMI group (11.41±1.94 pA/pF, n = 13) compa-ring with CON (17. 41±3. 13 pA/pF, n = 15), P <0. 01, while it was significantly increased in Statin group (16. 11±2. 43 pA/pF, n = 14) comparing with AMI group, P < 0. 01. Conclusions AMI induces significant down-regula-tion of Ina, I Ca-L and Ito. Pretreatment with

  5. Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status

    Energy Technology Data Exchange (ETDEWEB)

    Lyckesvärd, Madeleine Nordén, E-mail: madeleine.lyckesvard@oncology.gu.se [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden); Delle, Ulla; Kahu, Helena [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden); Lindegren, Sture [Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg (Sweden); Jensen, Holger [The PET and Cyclotron Unit Copenhagen University Hospital, Rigshospitalet (Denmark); Bäck, Tom [Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg (Sweden); Swanpalmer, John [Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg (Sweden); Elmroth, Kecke [Department of Oncology, Sahlgrenska Academy, University of Gothenburg (Sweden)

    2014-07-15

    Highlights: • We study DNA damage response to low-LET photons and high-LET alpha particles. • Cycling primary thyrocytes are more sensitive to radiation than stationary cells. • Influence of radiation quality varies due to cell cycle status of normal cells. • High-LET radiation gives rise to a sustained DNA damage response. - Abstract: Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ({sup 211}At), concentrated in the thyroid by the same mechanism as {sup 131}I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ({sup 60}Co) and alpha particles from {sup 211}At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of γH2AX decreased during the first 24 h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to {sup 211}At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1 Gy {sup 211}At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative

  6. Quantitative single-particle digital autoradiography with α-particle emitters for targeted radionuclide therapy using the iQID camera

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Brian W., E-mail: brian.miller@pnnl.gov [Pacific Northwest National Laboratory, Richland, Washington 99354 and College of Optical Sciences, The University of Arizona, Tucson, Arizona 85719 (United States); Frost, Sofia H. L.; Frayo, Shani L.; Kenoyer, Aimee L.; Santos, Erlinda; Jones, Jon C.; Orozco, Johnnie J. [Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 (United States); Green, Damian J.; Press, Oliver W.; Pagel, John M.; Sandmaier, Brenda M. [Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 and Department of Medicine, University of Washington, Seattle, Washington 98195 (United States); Hamlin, Donald K.; Wilbur, D. Scott [Department of Radiation Oncology, University of Washington, Seattle, Washington 98195 (United States); Fisher, Darrell R. [Dade Moeller Health Group, Richland, Washington 99354 (United States)

    2015-07-15

    Purpose: Alpha-emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50–80 μm), causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with α emitters may thus inactivate targeted cells with minimal radiation damage to surrounding tissues. Tools are needed to visualize and quantify the radioactivity distribution and absorbed doses to targeted and nontargeted cells for accurate dosimetry of all treatment regimens utilizing α particles, including RIT and others (e.g., Ra-223), especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, the ionizing-radiation quantum imaging detector (iQID) camera, for use in α-RIT experiments. Methods: The iQID camera is a scintillator-based radiation detection system that images and identifies charged-particle and gamma-ray/x-ray emissions spatially and temporally on an event-by-event basis. It employs CCD-CMOS cameras and high-performance computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, the authors evaluated its characteristics for α-particle imaging, including measurements of intrinsic detector spatial resolutions and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 ({sup 211}At) activity distributions in cryosections of murine and canine tissue samples. Results: The highest spatial resolution was measured at ∼20 μm full width at half maximum and the α-particle background was measured at a rate as low as (2.6 ± 0.5) × 10{sup −4} cpm/cm{sup 2} (40 mm diameter detector area

  7. 大剂量阿托伐他汀对老年急诊PCI术后造影剂肾病的保护作用%Effect of high dose atorvastatin in preventing contrast induced nephropathy in elderly patients underwent emergency PCI

    Institute of Scientific and Technical Information of China (English)

    董国峰; 吴尚勤; 姚青海; 陈炳伟; 杨琦; 杨培根

    2011-01-01

    Objective:To investigate the preventive effect of high dose statins (80 mg) for elderly patients on contrast induced nephropathy (CIN) after emergency percuta neous coronary intervention (PCI). Method:Before e mergency PCI, 85 cases (≥60 years) with acute myocardial infarction from September 2009 to March 2011 were ran domly divided into two groups: high dose atorvastatin group and regular dose atorvastatin group. On the basis of the hydration therapy, The patients of high dose atorvastatin groups received atorvastatin 80 mg orally instantly before emergency PCI and 40 mg once a day after emergency PCI in three days; The patients of regular dose atorv astatin groups received atorvastatin 20 mg orally instantly before emergency PCI and once a day after emergency PCI in three days. Then BUN, Scr, Ccr and incidence rate of CIN were measured and compared 24 hours and 72 hours after emergency PCI between groups.Contrast agents are used non ionic low osmolar contrast media iohexol and record usage. Result:72 hours after emergency PCI, BUN and Scr values and percentage of increase, Ccr val ues and percentage of decline and the incidence of CIN (13. 95% vs 33. 33%) in high dose atorvastatin group was significantly lower than regular dose atorvastatin group (P<0. 05). Conclusion: High dose atorvastatin can be of some preventive and protective value to CIN for the elderly patients after emergency PCI.%目的:探讨大剂量阿托伐他汀(80 mg)在预防老年(年龄≥60岁)急诊经皮冠状动脉内介入治疗术(急诊PCI)后造影剂相关肾病(CIN)的作用.方法:将2009-09-2011-03住院行急诊PCI术治疗的老年急性心肌梗死患者85例随机分为大剂量阿托伐他汀组和常规剂量阿托伐他汀组.2组患者在水化治疗的基础上,大剂量阿托伐他汀组在入院后即刻口服阿托伐他汀80 mg,急诊PCI术后3 d内每日口服阿托伐他汀40 mg;常规剂量阿托伐他汀组入院后即刻及急诊PCI术后3 d

  8. 普罗布考、阿托伐他汀对老年高血压病颈动脉粥样硬化的影响▲%Effect of Probucol Combined with Atorvastatin on Elderly Patients with Carotid Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    蒋美媛; 庞明; 陈敏; 严红; 余艳; 黎华

    2013-01-01

    Objective To observe the effect of probucol combined with atorvastatin on elderly hypertension patients with carotid atherosclerosis .Methods Sixty hypertension patients with thicken carotid intima-media thick-ness( IMT) and/or carotid atherosclerosis plaque were randomly divided into probucol group and probucol plus atorv -astatin group ( combination group ) according to their admission numbers ,30 cases in each group .The treatment lasted for six months .The changes of carotid IMT and carotid atheiosclerosis plaque area ,and levels of serum total cholester-ol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),oxidized low density lipoprotein(ox-LDL) and high-sensitivity C-reactive protein( hs-CRP) were detected in both groups before and after treatment .Results Carot-id IMT and plaque areas decreased significantly in both group after treatment (P<0.05),the decrease in the combina-tion group was more significant (P<0.01).TC,TG,LDL-C,ox-LDL and hs-CRP decreased significantly after treat-ment in both groups compared with those before treatment ,and the indices above in the combination group were signifi-cantly lower than those in the probucol group ( all P<0.01).Conclusion The therapy of probucol plus atorvastatin for the treatment of elderly hypertension patients with thicken carotid IMT and atherosclerosis plaque has significant effect without significant adverse reactions .%目的观察普罗布考联合阿托伐他汀对老年高血压病合并颈动脉粥样硬化的影响。方法将60例高血压病合并颈动脉内膜中层厚度( IMT)增厚和(或)颈动脉粥样硬化斑块患者,按入院就诊单双号分成普罗布考治疗组、普罗布考联合阿托伐他汀治疗组(联合组)各30例,疗程6个月。观察两组治疗前后颈动脉IMT厚度及颈动脉粥样硬化斑块面积变化及血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、氧化型低密度脂蛋白( ox

  9. 阿托伐他汀联合依折麦布对冠脉支架术后 LDL-C 未达标患者血脂水平及炎性因子影响的临床观察%Atorvastation joint ezetimibe’s clinical observation about coronary stent implantation in patients with LDL-C did not meet clinical lipid levels and inflammatory factors influence

    Institute of Scientific and Technical Information of China (English)

    孟繁宇; 施慧

    2015-01-01

    目的:探讨阿托伐他汀联合依折麦布对冠脉支架术后单用阿托伐他汀 LDL-C 未达标患者的血脂水平及炎性因子的影响。方法62例规律口服阿托伐他汀20 mg 每日一次4周以上的冠脉支架植入术后患者,且 LDL-C>1.8 mmol/L,随机分为对阿托伐他汀组40 mg 每日一次口服(a 组)和阿托伐他汀20 mg 每日一次联合依折麦布10 mg 每日一次口服(b 组)。两组患者均给予常规双重抗血小板聚集、基础疾病治疗,4周后测定患者:低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、高敏 c 反应蛋白、尿酸水平。结果强化降脂治疗后两组患者 LDL-C、TC、高敏 C 反应蛋白及尿酸水平,均较治疗前明显降低,具有统计学差异。强化降脂治疗前后两组 TG、HDL-C 水平无明显差异。强化降脂治疗后 b 组 LDL-C、TC、高敏 C 反应蛋白水平较 a 组明显降低,具有统计学差异。强化降脂治疗后两组患者尿酸水平无明显差异。结论常规剂量阿托伐他汀联合依折麦布比单独他汀剂量加倍更明显降低血脂、高敏 C 反应蛋白水平,减少炎症反应,改善血管内皮功能,使高危患者更多获益。%Objective To investigate the influence lipid levels and inflammatory factors in patients with atorvastatin ezetimibe combined with coronary stenting alone atorvastatin LDL-C did not meet.Methods 62 cases of oral law atorv-astatin 20 mg once daily for four weeks or more coronary stent implantation in patients,and LDL-C> 1.8 mmol/L, were randomly divided into groups of atorvastatin 40 mg orally once daily (a group)and atorvastatin 20 mg once daily combined with ezetimibe 10 mg once daily orally (b group).All patients were treated with conventional dual anti-plate-let aggregation,the underlying disease treatment,measured four weeks after patients:low-density lipoprotein cholester

  10. 贝前列素钠联合阿托伐他汀治疗老年糖尿病肾病的临床效果%Clinical Effects Beraprost Sodium Hormone Therapy with Atorvastatin for Diabetic Nephropathy in Elderly Patients

    Institute of Scientific and Technical Information of China (English)

    张艳; 杨艳丽; 赵婕; 钟大平

    2016-01-01

    Objective To investigate the clinical effects of beraprost sodium hormone therapy with atorv-astatin for diabetic nephropathy in elderly patients.Methods Total of 124 elderly patients with diabetic nephropathy were selected from PLA 324th Hospital during Dec.2012 and Dec.2014,and were randomly divided into observation group and control group,62 patients each.The control group was treated with bera-prost sodium,40 μg per time,3 times a day,oral;the observation group was given beraprost sodium combined with atorvastatin therapy,20 mg per time,1 time a day,oral.Both groups were treated for 8 weeks,and the clinical results of the two groups of patients were compared.Results After treatment,high density lipoprotein cholesterol(HDL-C) of the observation group was higher than the control group[(1.22 ±0.03) mmol/L vs (1.05 ±0.42) mmol/L],low density lipoprotein cholesterol ( LDL-C) was lower than the control group [(1.3 ±0.6) mmol/L vs (2.7 ±1.3) mmol/L],the difference was statistically significant(P 0.05).Conclusion Beraprost sodium combined with atorvastatin combination thera-py is safe and effective for diabetic nephropathy in elderly patients ,which can significantly improve the clini-cal symptoms and is worth of promotion in clinical practice .%目的:探讨贝前列素钠联合阿托伐他汀治疗老年糖尿病肾病的临床效果。方法选取2012年12月至2014年12月解放军第三二四医院收治的124例老年糖尿病肾病患者为研究对象,依据随机数字表法分为观察组和对照组,各62例。对照组采用贝前列素钠治疗,每次40μg,每日3次,口服;观察组在对照组的基础上联合阿托伐他汀治疗,每次20 mg,每日1次,口服。两组患者均持续治疗8周。比较两组患者的临床效果。结果治疗后,观察组高密度脂蛋白胆固醇高于对照组[(1.22±0.03) mmol/L 比(1.05±0.42) mmol/L],低密度脂蛋白胆固醇低于对照组[(1.3±0.6) mmol/L