WorldWideScience

Sample records for astatine

  1. Organic chemistry of astatine

    International Nuclear Information System (INIS)

    The paper surveys the investigations on the chemical behaviour of astatine in organic systems and deals with the preparation and identification of its organic compounds. A discussion is given on some of the physico-chemical properties of these compounds determined by extrapolation techniques as well as by direct measurement. The biomedical importance of 211At-labelled compounds is briefly referred to. (authors)

  2. 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.)

  3. 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

  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. Dosimetrical considerations in astatine-211 radioimmunotherapy

    International Nuclear Information System (INIS)

    Several dosimetrical quantities have been suggested for use in alpha-particle dosimetry. To evaluate the expected biological effect when using these quantities, a Monte Carlo program was set to register the single-event distribution of both specific energy and alpha-particle track length to a cell nucleus (r=5.6 μm). Distributions were acquired for both 'bound' (simulating the effect of 211At-labelled antibodies bound to antigens on cell surfaces (r=7.0 μm)) as well as 'non-bound' (simulating 211At-labelled antibodies that have not bound to a cell) astatine-211. From these distributions, various theoretical cell survival curves were established for 3 different dosimetrical quantities, i.e. specific energy, number of alpha-particle hits and total track length. The survival curves for all quantities are presented for the corresponding mean absorbed dose in order to facilitate comparisons of the expected effects of using the 3 different quantities for both distributions of 211At decays. The theoretical survival curves presented here could, combined with experiments using 'bound' and 'non-bound' 211At in a single-cell suspension, reveal which dosimetrical quantity is most suitable for 211 At-radioimmunotherapy. (author)

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

    OpenAIRE

    Fry, C; Thoennessen, M

    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.

  7. 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)

  8. 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

  9. Scrutinizing "Invisible" astatine: A challenge for modern density functionals.

    Science.gov (United States)

    Sergentu, Dumitru-Claudiu; David, Grégoire; Montavon, Gilles; Maurice, Rémi; Galland, Nicolas

    2016-06-01

    The main-group 6p elements did not receive much attention in the development of recent density functionals. In many cases it is still difficult to choose among the modern ones a relevant functional for various applications. Here, we illustrate the case of astatine species (At, Z = 85) and we report the first, and quite complete, benchmark study on several properties concerning such species. Insights on geometries, transition energies and thermodynamic properties of a set of 19 astatine species, for which reference experimental or theoretical data has been reported, are obtained with relativistic (two-component) density functional theory calculations. An extensive set of widely used functionals is employed. The hybrid meta-generalized gradient approximation (meta-GGA) PW6B95 functional is overall the best choice. It is worth noting that the range-separated HSE06 functional as well as the old and very popular B3LYP and PBE0 hybrid-GGAs appear to perform quite well too. Moreover, we found that astatine chemistry in solution can accurately be predicted using implicit solvent models, provided that specific parameters are used to build At cavities. © 2016 Wiley Periodicals, Inc. PMID:27059181

  10. 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.

  11. 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

  12. Astatine-211: production, injection into monoclonal antibodies radiological effect, possible application to cancer treatment

    International Nuclear Information System (INIS)

    Methods developed in the Laboratory of Nuclear Problems, JINR, for producing astatine-211 and injecting it into monoclonal antibodies are described. The use of its diethylene triamine penta-acetic acid complex is shown to be the most effective method of injecting astatine into a biomolecules. The biological effect of the α-particles emitted from the astatine-211 is investigated using Chinese hamster fibroblasts and Ehrlich carcinoma cells. It is established that the mitotic activity depression, number of degenerating cells, number of cells with chromosome aberrations, and cellular surviving fraction depend on the concentration of the radionuclide in the medium 'in vitro'. The RBE of α-particles in comparison with 60Co γ-rays is 3. Injection of astatine-211 absorbed on tellurium particles into mice with ascitic tumors resulted in prolongation of their life or elimination of the tumors. (author). 39 refs, 7 figs

  13. 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...

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

    Science.gov (United States)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom; Jensen, Holger; Palm, Stig; Lindegren, Sture

    2015-07-01

    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 that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies.

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

    DEFF Research Database (Denmark)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom; Jensen, Holger; Palm, Stig; Lindegren, Sture

    2015-01-01

    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......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...... challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies....

  16. 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

  17. 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.)

  18. 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

  19. 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...

  20. Direct astatination of a tumour-binding protein, human epidermal growth factor, using nido-carborane as a prosthetic group

    International Nuclear Information System (INIS)

    A method for direct astatine labeling of proteins has been investigated. Binding sites for astatine were created by coupling of a nido-carborane derivative to a protein, the human epidermal growth factor (hEGF), using two different conjugation methods - by glutaraldehyde cross-linking or by introduction of sulfohydryl groups by Traut's reagent with subsequent linking of ANC-1 with m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester. The conjugates were astatinated using the Chloramine-T method in high yield. The best labeling was obtained by the glutaraldehyde conjugate with an average yield of 68 ± 9%. In vitro stability tests indicated that the glutaraldehyde conjugated label was as stable as hEGF labeled with astatobenzoate. (author)

  1. Labelling prospects of astatine-211 with immunoglobulins (IgG): some general considerations

    International Nuclear Information System (INIS)

    The tumour therapeutic potential of the short lived alpha emitting radiohalogen 211At has been already been well recognised in the field of radioimmuno therapy. There is no evidence as such to show that astatine itself is a tumour seeking isotope. Therefore it has to be tagged to tumour seeking compound such as a drug or a protein preferably an antibody (IgG). In this communication, the labelling parameters which are required to be investigated for obtaining a stable product which could be useful as radioimmuno therapeutic agent, are described. (author). 6 refs

  2. 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].

  3. Extraction of 211At-astatine from hydrochloric acid solutions by means of TOPO, TBP, and triphenylphosphine

    International Nuclear Information System (INIS)

    The extraction behaviour of astatine was studied under defined conditions from hydrochloride acid solutions (cHCl>0.1 M or 1 and 2M). Therefore other effects like adsorption, reduction or hydrolysis can be excluded. The present work describes the extraction with tri- n- octylphosphinoxide (TOPO), tri- n-butylphosphate (TBP) and tri-phenylphosphine in chloroform. (orig.)

  4. No-carrier-added astatination of N-succinimidyl-3-(tri-n-butylstannyl) benzoate (ATE) via electrophilic destannylation

    International Nuclear Information System (INIS)

    The no-carrier-added synthesis of N-succinimidyl 3-[211At]astato-benzoate from N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE) is described. The nature of the solvent in which the 211At was isolated from the target was an important factor influencing both the radiochemical yields and the nature of the incorporated astatine activity. (orig.)

  5. 211At-Rh(16-S4-diol) complex as a precursor for astatine radiopharmaceuticals

    International Nuclear Information System (INIS)

    211At is one of the most promising radionuclides in α-radioimmunotherapy (α-RIT). Unfortunately, biomolecules labeled by direct electrophilic astatination are unstable due to the rapid loss of 211At under both in vitro and in vivo conditions. The present paper describes the results of our studies on attaching At- to the rhodium(III) complex with thioether ligand: 1,5,9,13-etrathiacyclohexadecane-3,11-diol (16-S4-diol). Rh3+ was chosen as a moderately soft metal cation which should form very strong bonds with soft At- anions, but first of all because of the kinetic inertness of low spin rhodium(III) d6 complexes. The 16-S4-diol ligand was selected due to formation of stable complexes with Rh3+. The experiments related to optimization of the reaction conditions were performed with the 131I, basing on a chemical similarity of I- to At-. The experiments with 211At were then carried out under the conditions found optimal for I-. The preliminary results are promising, and indicate a possibility for astatination of biomolecules by using the 211At-Rh(16-S4-diol) complex

  6. 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

  7. 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

  8. 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

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

    CERN Document Server

    Rothe, Sebastian; Nörtershäuser, W

    This doctoral thesis describes the extension of the resonance ionization laser ion source RILIS at ISOLDE, CERN, by the addition of an all-solid state tuneable 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.

  10. 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.

  11. 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.

  12. Stability and in vivo behavior of Rh[16aneS4-diol]211At complex: A potential precursor for astatine radiopharmaceuticals

    International Nuclear Information System (INIS)

    Introduction: The heavy halogen 211At is of great interest for targeted radiotherapy because it decays by the emission of short-range, high-energy α-particles. However, many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking other 211At labeling strategies. One relatively unexplored approach is to utilize prosthetic groups based on astatinated rhodium (III) complex stabilized with a tetrathioether macrocyclic ligand – Rh[16aneS4-diol]211At. The purpose of the current study was to evaluate the in vitro and in vivo stability of this complex in comparison to its iodine analog – Rh[16aneS4-diol]131I. Methods: Rh[16aneS4-diol]211At and Rh[16aneS4-diol]131I complexes were synthesized and purified by HPLC. The stability of both complexes was evaluated in vitro by incubation in phosphate-buffered saline (PBS) and human serum at different temperatures. The in vivo behavior of the two radiohalogenated complexes was assessed by a paired-label biodistribution study in normal Balb/c mice. Results: Both complexes were synthesized in high yield and purity. Almost no degradation was observed for Rh[16aneS4-diol]131I in PBS over a 72 h incubation. The astatinated analog exhibited good stability in PBS over 14 h. A slow decline in the percentage of intact complex was observed for both tracers in human serum. In the biodistribution study, retention of 211At in most tissues was higher than that of 131I at all time points, especially in spleen and lungs. Renal clearance of Rh[16aneS4-diol]211At and Rh[16aneS4-diol]131I predominated, with 84.1 ± 2.3% and 94.6 ± 0.9% of injected dose excreted via the urine at 4 h. Conclusions: The Rh[16aneS4-diol]211At complex might be useful for constructing prosthetic groups for the astatination of biomolecules and further studies are planned to evaluate this possibility

  13. 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

  14. Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter

    International Nuclear Information System (INIS)

    The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET α-emitter astatine-211 (211At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 (123I), 340-fold for technetium-99m pertechnetate (99mTcO4-) and 60-fold for 211At. Cellular 211At accumulation was found to be dependent on extracellular Na+ ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and 99mTcO4- uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated 211At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and 211At were rapidly (apparent t1/2 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times (123I), 25 times (99mTcO4-) and 10 times (211At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of 123I and 211At, respectively, was found in NIS tumours by region of interest analysis (n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for 123I, 5.2 h for 211At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBqtumour for 131I and 50.3 Gy/MBqtumour for 211At). In

  15. Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter

    Energy Technology Data Exchange (ETDEWEB)

    Petrich, T.; Helmeke, H.-J.; Meyer, G.J.; Knapp, W.H.; Poetter, E. [Department of Nuclear Medicine, Medizinische Hochschule Hannover (Germany)

    2002-07-01

    The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET {alpha}-emitter astatine-211 ({sup 211}At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 ({sup 123}I), 340-fold for technetium-99m pertechnetate ({sup 99m}TcO{sub 4}{sup -}) and 60-fold for {sup 211}At. Cellular {sup 211}At accumulation was found to be dependent on extracellular Na{sup +} ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and {sup 99m}TcO{sub 4}{sup -} uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated {sup 211}At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and {sup 211}At were rapidly (apparent t{sub 1/2} 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times ({sup 123}I), 25 times ({sup 99m}TcO{sub 4}{sup -}) and 10 times ({sup 211}At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of {sup 123}I and {sup 211}At, respectively, was found in NIS tumours by region of interest analysis (n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for {sup 123}I, 5.2 h for {sup 211}At) and

  16. Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211-labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Chen, Yun; Kornblit, Brian; Hamlin, Donald K; Sale, George E; Santos, Erlinda B; Wilbur, D Scott; Storer, Barry E; Storb, Rainer; Sandmaier, Brenda M

    2012-02-01

    To reduce toxicity associated with external γ-beam radiation, we investigated radioimmunotherapy with an anti-CD45 mAb labeled with the α-emitter, astatine-211 ((211)At), as a conditioning regimen in dog leukocyte antigen-identical hematopoietic cell transplantation (HCT). Dose-finding studies in 6 dogs treated with 100 to 618 μCi/kg (211)At-labeled anti-CD45 mAb (0.5 mg/kg) without HCT rescue demonstrated dose-dependent myelosuppression with subsequent autologous recovery, and transient liver toxicity in dogs treated with (211)At doses less than or equal to 405 μCi/kg. Higher doses of (211)At induced clinical liver failure. Subsequently, 8 dogs were conditioned with 155 to 625 μCi/kg (211)At-labeled anti-CD45 mAb (0.5 mg/kg) before HCT with dog leukocyte antigen-identical bone marrow followed by a short course of cyclosporine and mycophenolate mofetil immunosuppression. Neutropenia (1-146 cells/μL), lymphopenia (0-270 cells/μL), and thrombocytopenia (1500-6560 platelets/μL) with prompt recovery was observed. Seven dogs had long-term donor mononuclear cell chimerism (19%-58%), whereas 1 dog treated with the lowest (211)At dose (155 μCi/kg) had low donor mononuclear cell chimerism (5%). At the end of follow-up (18-53 weeks), only transient liver toxicity and no renal toxicity had been observed. In conclusion, conditioning with (211)At-labeled anti-CD45 mAb is safe and efficacious and provides a platform for future clinical trials of nonmyeloablative transplantation with radioimmunotherapy-based conditioning. PMID:22134165

  17. Treatment of cultured glioma cells with the EGFR-TKI gefitinib (''Iressa'', ZD1839) increases the uptake of astatinated EGF despite the absence of gefitinib-mediated growth inhibition

    International Nuclear Information System (INIS)

    The EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor) gefitinib (''Iressa'', ZD1839), a reversible growth inhibitor of EGFR-expressing tumour cells, has been shown to enhance the antitumour effect of ionising radiation, and also to increase the uptake of radioiodinated EGF. Thus, combination of gefitinib treatment and radionuclide targeting is an interesting option for therapy of brain tumours that are difficult to treat with conventional methods. The aim of this study was to evaluate how pre-treatment with gefitinib affects binding of astatinated EGF (211At-EGF) to cultured glioma U343 cells, which express high levels of EGFR. The growth of U343 cells in the presence of gefitinib was investigated, and it was found that gefitinib does not significantly inhibit the growth of these cells. Nevertheless, the uptake of 211At-EGF in U343 cells was markedly increased (up to 3.5 times) in cells pre-treated with gefitinib (1 μM). This indicates that a combination of gefitinib treatment and radionuclide targeting to EGFR might be a useful therapeutic modality, even for patients who do not respond to treatment with gefitinib alone. (orig.)

  18. Astatination of closo-dodecaborate(2-) anion

    Czech Academy of Sciences Publication Activity Database

    Orlova, A.; Lebeda, Ondřej; Tolmachev, V.; Lundquist, H.; Carlsson, J.; Sjöberg, S.

    Cambridge : The Royal Society of Chemistry , 2000 - (Davidson, M.; Hughes, A.; Marder, T.; Wade , K.), s. 144-147 [Conference "Contemporary Boron Chemistry ". Durham (GB), 11.07.1999-15.07.1999] Institutional research plan: CEZ:AV0Z1048901 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  19. Process for producing astatine-211 for radiopharmaceutical use

    International Nuclear Information System (INIS)

    A one-step chemical manipulation is described in combination with a distillation and collection process for producing At-211 comprising; a. providing a target of irradiated Bismuth coated to a predetermined thickness of a backing member, b. providing a vapor-producing still operably connected with a condenser that has a water cooled condensate collector formed of a dry silica gel mesh maintained at a temperature above the freezing point of water, and providing an effluent gas filter that is operably connected to receive effluent gas from the condenser, c. heating the target in the still at a temperature in the range of about 6300-6800C for a time period in the range of 50 to 80 minutes, to evole At-211 vapor from the target, c. providing a dry carrier gas having an oxygen concentration that is sufficient to form Bi/sub 2/O/sub 3/ thereby to essentially preclude vaporization of Bi metal, passing the carrier gas through the still to carry the At-211 vapor to the condenser, and to carry effluent from the condenser to the effluent gas filter, e. eluting At-211 from the condensate collector of the condenser with a controlled volume of eluent containing predetermined solvents that are compatible with a given desired radiopharmaceutical procedure, and f. collecting the At-211 in the controlled volume of eluent for use in the given radiopharmaceutical procedure

  20. 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.

  1. 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.

  2. Astatination of nanoparticles containing silver as possible carriers of 211At

    Czech Academy of Sciences Publication Activity Database

    Lebeda, Ondřej; Kučka, Jan; Hrubý, Martin; Koňák, Čestmír; Kozempel, Ján

    2006-01-01

    Roč. 64, - (2006), s. 201-206. ISSN 0969-8043 R&D Projects: GA AV ČR KJB4048302; GA AV ČR KJB4050408 Institutional research plan: CEZ:AV0Z1048901 Keywords : nanoparticles * 211AT * Atalpha particle therapy Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 0.924, year: 2006

  3. 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.

  4. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani; Kenoyer, Aimee L.; Hylarides, Mark; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sophia; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Ted; Laird, Kelley L.; Till, B. G.; Back, Tom; Sandmaier, B. M.; Pagel, John M.; Press, Oliver W.

    2015-03-26

    Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

  5. 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...

  6. Inactivation of human osteosarcoma cells in vitro by {sup 211}At-TP-3 monoclonal antibody: Comparison with astatine-211 and external-beam X rays

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, R.H. [Univ. of Oslo (Norway)]|[Institute for Cancer Research, Oslo (Norway); Bruland, O.S. [Institute for Cancer Research, Oslo (Norway); Hoff, P.; Alstad, J. [Univ. of Oslo (Norway); Lindmo, T. [Institute for Cancer Research, Oslo (Norway); Rofstad, E.K. [Norwegian Institute of Technology, Trondheim (Norway)

    1994-08-01

    The potential usefulness of {alpha}-particle radioimmunotherapy in the treatment of osteosarcoma was studied in vitro by using the monoclonal antibody TP-3 and cells of three human osteosarcoma cell lines (OHS, SAOS and KPDX) differing in antigen expression. Cell survival curves were established after treatment with (a) {sup 211}At-TP-3 of different specific activities, (b) {sup 211}At-labeled bovine serum albumin (BSA), (c) free {sup 211}At and (d) external-beam X rays. The three osteosarcoma cell lines showed similar survival curves, whether treated with external-beam X rays, {sup 211}At-BSA or free {sup 211}At. The D{sub o}`s were lower for free {sup 211}At than for {sup 211}At-BSA. The survival curves for {sup 211}At-TP-3 treatment, on the other hand, differed significantly among the cell lines, suggesting that sensitivity to {sup 211}At-TP-3 treatment was governed by cellular properties other than sensitivity to external-beam X rays. The cellular property most important for sensitivity to {sup 211}At-TP-3 treatment was the antigen expression. Cell inactivation after {sup 211}At-TP-3 treatment increased substantially with increasing specific activity of the {sup 211}At-TP-3. At high specific activities, the cytotoxic effect of {sup 211}At-TP-3 was significantly higher than that of {sup 211}At-BSA. In conclusion, {sup 211}At-TP-3 has the potential to give clinically favorable therapeutic ratios in the treatment of osteosarcoma. 39 refs., 5 figs., 2 tabs.

  7. Shelf-Life of ɛ-Lysyl-3-(Trimethylstannyl)Benzamide Immunoconjugates, Precursors for 211At Labeling of Antibodies

    OpenAIRE

    Aneheim, Emma; Halleröd, Jenny; Albertsson, Per; Jensen, Holger; Holgersson, Stellan; Lindegren, Sture

    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 and the complex radiochemistry of 211At are major obstacles for research and prospective clinical applications. In the present study, astatination of immunoconjugates, already prepared well in advance...

  8. 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 ...

  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. 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

  11. Separation of 211At from irradiated bismuth target and labelling of a model protein

    International Nuclear Information System (INIS)

    Astatine-211 is a promising radionuclide for therapeutic use in nuclear medicine. An efficient method (70%) for radiochemical separation from the irradiated Bi-target has been described. The level of Bi contamination in the purified 2'11At-solution was estimated. Finally labelling of a model protein has been tried. (author). 14 refs

  12. 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

  13. $\\beta$-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.

  14. 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.

  15. 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

  16. Radiohalogenation of biomolecules. An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution

    International Nuclear Information System (INIS)

    Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging, and in radionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on 211At and 124I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two. Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap was developed for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[211At]astato-2'-deoxyuridine (AUdR) and N-succinimidyl-4-[211At]astatobenzoate (SAB) were synthesized in 95% respectively 90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(1-) conjugate. The overall labeling yields were 3.5% for direct labeling, 44% for SAB and 70% for the hEGF-nido-carborane conjugate. A new route to N-succinimidyl 3- and 4- [124I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxyam ide, a peripheral-type benzodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[124I]iodo-2'-deoxyuridine (IUdR) is presented. The closo-dodecaborate anion was evaluated as prosthetic group for radioiodination of macromolecules

  17. 211At production and recovery: first results of a new start

    International Nuclear Information System (INIS)

    Full text: 211At is the only alpha-emitting isotope which can be introduced into organic molecular structures by covalent chemical binding and possesses superior decay characteristics for therapeutic applications when compared with other alpha emitters. However, its production requires a minimum of 27,5 MeV alpha-particles, which are relatively rarely available. In view of the revival of alpha-therapy approaches a production of 211At has been set up at the MHH cyclotron (MC-35). The first aim of this project was to establish a target- and work-up-system for the reliable production of several ten MBq-quantities of 211At for animal- and cell-research. An aluminum-target-system holds a 1.3 cm diameter Bi-disc of 0.25 mm thickness. The disk is pressed onto a the aluminum backing with 2 tons/cm2. The front is covered with a 125 μm Al foil, cooled by a He jet which is separated from the vacuum by a 250 μm Ti foil. Starting with 27.5 MeV alpha-particles the resulting target-energy is 25 MeV. This relatively low energy is chosen to avoid any contamination with 210At and 210Po in the first experimental period. A beam current of 10 μA for 15 min (9 mCoulomb) yields 16.4 MBq 211At theoretically. Astatine is recovered from the target by a dry distillation technique, using various gases as a transport support-medium. The small all-quartz distillation-apparatus is heated up to 900 oC. Astatine is recovered in a small cool able vessel containing various trapping media. Distillation and trapping can be monitored with small radioactivity monitors. The whole system fits in a cubical 0.5 m glove box. Continuous monitoring of the distillation process allowed to optimize the heating rate, the transport support-medium and its flow-rate. Various trapping solutions were tested for their efficiency. Different beam dispersion in the target seems to influence the release and distillation of astatine from the molten bismuth-target. Two different release patterns were observed. The first

  18. 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

  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. 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

  1. 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.

  2. A route for polonium 210 production from alpha-particle irradiated bismuth-209 target

    International Nuclear Information System (INIS)

    A method is proposed for production of polonium-210 via the 209Bi(α,3n)210 At nuclear reaction. Bombardment of a bismuth-209 target was performed with a 37 MeV alpha-particle beam that leads to the production of astatine-210 (T1/2 = 8.1 h), which decays to polonium-210. It is purified from the bismuth target matrix by employing liquid-liquid extraction using tributyl phosphate (TBP) in para-xylene from 7 M hydrochloric acid. Back extraction of polonium-210 was performed by 9 M nitric acid. This method allows to purify a tracer amount of Po-210 (2.6 x 10-13 mol) from macroscopic amount of Bi (2.8 x 10-2 mol).

  3. Effective bond orders from two-step spin–orbit coupling approaches: The I{sub 2}, At{sub 2}, IO{sup +}, and AtO{sup +} case studies

    Energy Technology Data Exchange (ETDEWEB)

    Maurice, Rémi, E-mail: remi.maurice@subatech.in2p3.fr; Montavon, Gilles [SUBATECH, CNRS UMR 6457, IN2P3/EMN Nantes/Université de Nantes, 4 rue Alfred Kastler, BP 20722, 44307 Nantes Cedex 3 (France); Réal, Florent; Gomes, André Severo Pereira; Vallet, Valérie [Laboratoire PhLAM, CNRS UMR 8523, Université de Lille, 59655 Villeneuve d’Ascq Cedex (France); Galland, Nicolas [CEISAM, UMR CNRS 6230, Université de Nantes, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3 (France)

    2015-03-07

    The nature of chemical bonds in heavy main-group diatomics is discussed from the viewpoint of effective bond orders, which are computed from spin–orbit wave functions resulting from spin–orbit configuration interaction calculations. The reliability of the relativistic correlated wave functions obtained in such two-step spin–orbit coupling frameworks is assessed by benchmark studies of the spectroscopic constants with respect to either experimental data, or state-of-the-art fully relativistic correlated calculations. The I{sub 2}, At{sub 2}, IO{sup +}, and AtO{sup +} species are considered, and differences and similarities between the astatine and iodine elements are highlighted. In particular, we demonstrate that spin–orbit coupling weakens the covalent character of the bond in At{sub 2} even more than electron correlation, making the consideration of spin–orbit coupling compulsory for discussing chemical bonding in heavy (6p) main group element systems.

  4. Effective bond orders from two-step spin–orbit coupling approaches: The I2, At2, IO+, and AtO+ case studies

    International Nuclear Information System (INIS)

    The nature of chemical bonds in heavy main-group diatomics is discussed from the viewpoint of effective bond orders, which are computed from spin–orbit wave functions resulting from spin–orbit configuration interaction calculations. The reliability of the relativistic correlated wave functions obtained in such two-step spin–orbit coupling frameworks is assessed by benchmark studies of the spectroscopic constants with respect to either experimental data, or state-of-the-art fully relativistic correlated calculations. The I2, At2, IO+, and AtO+ species are considered, and differences and similarities between the astatine and iodine elements are highlighted. In particular, we demonstrate that spin–orbit coupling weakens the covalent character of the bond in At2 even more than electron correlation, making the consideration of spin–orbit coupling compulsory for discussing chemical bonding in heavy (6p) main group element systems

  5. Different ways to improve the clinical effectiveness of radioimmunotherapy in solid tumors

    Directory of Open Access Journals (Sweden)

    Chatal Jean-Francois

    2009-09-01

    Full Text Available Radioimmunotherapy (RIT has been proven effective in the treatment of radiosensitive non-Hodgkin lymphoma but, for radioresistant solid tumors, new approaches are necessary to improve the clinical effectiveness. A real improvement has been the introduction of the pretargeting technology which appeared to be able to significantly increase tumor-to-normal organ uptake ratios.Another very promising approach consists in associating RIT with other treatment modalities. Finally the use of alpha particle-emitting radionuclides such as astatin-211 or bismuth-213 (alpha-RIT should allow to efficiently eradicate disseminated microscopic clusters of tumor cells or isolated tumor cells which fit well with the short path length of alpha particles.

  6. Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model

    DEFF Research Database (Denmark)

    Eriksson, Sophie E; Elgström, Erika; Bäck, Tom;

    2014-01-01

    UNLABELLED: Alpha-particle emitters, such as astatine-211 (211At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 (177Lu), have a longer path length and are considered better for...... small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon...... carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96...

  7. 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...

  8. 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

  9. 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....

  10. An improved synthesis of an 125I and 211At labelled benzamide for melanoma imaging

    International Nuclear Information System (INIS)

    Recent studies have indicated that benzamides can exhibit affinity for malignant melanoma and may be exploited diagnostically in the treatment of this cancer. Radioiodinated N-(2-diethylaminoethyl)-3-[123I/131I]iodo-4-methoxybenzamide (*I-IMBA) is a benzamide with promising diagnostic properties. A new synthesis procedure was developed to obtain 125I-IMBA suitable for use in vivo. The assets of the procedure include the use of less toxic reagents and better reproducible results when radiolabelling the precursor. The procedure also facilitates the synthesis of the astatinated N-(2-diethylaminoethyl)-3-[211At]astatine-4-methoxybenzamide (211At-AMBA), a new benzamide with a therapeutic potential. The regiospecific no-carrier-added 125I- and 211At-labeling of the benzamide is performed by demetalation of an organotin precursor. Using tributylstannyl as a leaving group, the radiochemical yield obtained after 15 minutes of reaction was 70 %-90 % for both 125I-IMBA and 211At-AMBA. The labelling was performed in a solution of MeOH:AcOH with NCS as the oxidising agent. The organotin precursor N-(2-diethylaminoethyl)-3-(tri-n-butylstannyl)-4-methoxy-benzamide was synthesized from 3-bromo-4-methoxybenzoic acid, with n-BuLi (2 eq) and Bu3SnCl (1 eq) in THF, giving 3-(tri-n-butylstannyl)-4-methoxybenzoic acid. The amide function was introduced by converting the acid group into an active N-succinimidyl-ester, a good leaving group in the reaction with 2-(diethylamino)ethylamine. The overall yield of the organotin precursor was 65 %

  11. 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.

  12. The biokinetics of alpha-particle emitting radiopharmaceuticals

    International Nuclear Information System (INIS)

    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 211At (T1/2 7.21 h), 212Bi (T1/2 1 h) or 213Bi (T1/2 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 211At 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 212Bi-labelled radiopharmaceuticals. The available data for both 211At and 212Bi radiopharmaceuticals are reviewed. Cautious generic biokinetic models for inorganic and simple organic compounds of 211At and 212Bi; for [211At]-, and [212Bi]-biphosphonates and for [211At]-, and [212Bi]-monoclonal antibodies, are proposed for use in general radiological protection when compound-specific data are not available. (orig.)

  13. The radiolabeled monoclonal antibodies in immunoscintigraphy and radioimmunotherapy: current state and perspectives

    International Nuclear Information System (INIS)

    The antibodies can be satisfactorily labelled with technitium-99 m or indium-111 for tumor immunoscintigraphy. The immunoscintigraphy is not useful for the primary tumor diagnosis. It can be useful for the diagnosis of the some cancer extension and for recurrent tumor visualization. The immunoscintigraphy is widely competed with Positron Emission Tomography (PET) which gives accurate results. In the future the immunoscintigraphy, in pre-therapeutic stage, contribute to the estimation of the dose delivered to the tumor and to normal organs for adopting or not a radioimmunotherapy. The antibodies can also be labeled with Iodine-131 for an application in radioimmunotherapy (RIT). The RIT is efficient in the non-Hodgkin's lymphoma treatment because of their great radiosensitivity. Until now the results have been very modest in solid tumor treatment but methodological and biotechnological progresses have to improve the efficiency especially for the small tumors. In the future iodine-131 which requires the confinement (very expensive) of patients will be substituted by yttrium-90 beta emitter, more energetic than iodine-131 and can be injected in walking case. In the long term, the alpha emitter radionuclides (astatine-211 or bismuth-213) can be used for hematologic cancer treatment. In conclusion the future of radiolabeled monoclonal antibodies is essentially therapeutic. The radioimmunotherapy associated to the chemotherapy give promising perspectives for the radiosensitive cancer treatment and in general small solid tumor treatment (F.M.)

  14. Biological toxicity of intracellular radionuclide decay. Part of a coordinated programme on radiation biology of Auger emitters and their therapeutic applications

    International Nuclear Information System (INIS)

    Internal radiotherapy should be performed with short-lived radionuclides which emit high LET radiation and short ranged radiation, and accumulated within cancers. Based on these considerations, several radionuclides (tritium, copper-64, gallium-67, iodine-123, iodine 125, iodine-131 and astatine-211) were chosen and their toxicity was assessed using cell division in mammalian cultured cells as a criterion. It was apparent that the toxic effects obtained with 125I greatly exceeded those observed in cells treated with any other radionuclides. The possible hypotheses to explain the excessive radiosensitivity of 125I were discussed in relation to microdosimetry calculation. It was also found that the division delay induced by radionuclide decay is primarily due to damage to the cell nucleus but not to the plasma membrane. The key problem remains the development of agents which can serve as carriers for radionuclide accumulation within tumors. Although several promising approaches (Synkavit, tamoxifen, iododeoxyuridine, antibodies, liposomes) were investigated, only 125I-labelled Synkavit would be desirable for clinical application

  15. 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 ...

  16. 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.)

  17. Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

    International Nuclear Information System (INIS)

    Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 (211At-cMAb U36). Effects on 211At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with 211At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced 211At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

  18. 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

  19. 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.

  20. Proceedings of transuranium elements

    International Nuclear Information System (INIS)

    The identification of the first synthetic elements was established by chemical evidence. Conclusive proof of the synthesis of the first artificial element, technetium, was published in 1937 by Perrier and Segre. An essential aspect of their achievement was the prediction of the chemical properties of element 43, which had been missing from the periodic table and which was expected to have properties similar to those of manganese and rhenium. The discovery of other artificial elements, astatine and francium, was facilitated in 1939-1940 by the prediction of their chemical properties. A little more than 50 years ago, in the spring of 1940, Edwin McMillan and Philip Abelson synthesized element 93, neptunium, and confirmed its uniqueness by chemical means. On August 30, 1940, Glenn Seaborg, Arthur Wahl, and the late Joseph Kennedy began their neutron irradiations of uranium nitrate hexahydrate. A few months later they synthesized element 94, later named plutonium, by observing the alpha particles emitted from uranium oxide targets that had been bombarded with deuterons. Shortly thereafter they proved that is was the second transuranium element by establishing its unique oxidation-reduction behavior. The symposium honored the scientists and engineers whose vision and dedication led to the discovery of the transuranium elements and to the understanding of the influence of 5f electrons on their electronic structure and bonding. This volume represents a record of papers presented at the symposium

  1. 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.

  2. Development and radiotherapeutic application of 211At-labeled radiopharmaceuticals. Progress report, March 1, 1981-February 28, 1982

    International Nuclear Information System (INIS)

    This project is concerned with developing the potential of alpha-emitting radionuclides as agents for radiotherapy. Alpha-emitters seem ideally suited for his application because their high linear energy transfer and short range permit the deposition of considerable energy in a very small volume of tissue. Unlike the beta particles of 131I which have a range of about 1 to 2 mm in tissue, 5 to 7 MeV alpha particles would traverse only a few cell diameters. Among the available alpha-emitters, 211At appears most promising for therapeutic applications because, (1) it has some chemical similarities to iodine, an element that can readily be incorporated into numerous proteins and peptides, (2) it has a half-life that is long enough to permit chemical manipulation yet short enough to minimize destruction of healthy cells due to degradation of the label over time, (3) it can be produced conveniently using a cyclotron, and (4) alpha emission is associated with 100% of its decays with no accompanying beta emission. In the past year the evaluation of an astatine-tellurium colloid as an agent for the destruction of malignant ascites has been completed. The therapeutic efficacy of 211At-tellurium colloid has been compared with that of several beta-emitting radiocolloids. Studies on the application of monoclonal antibodies as carriers for selective delineation and destruction of malignant cell populations have also been initiated

  3. 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)

  4. 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. \\...

  5. Effect of cetuximab in combination with alpha-radioimmunotherapy in cultured squamous cell carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Nestor, Marika, E-mail: marika.nestor@bms.uu.s [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden); Sundstroem, Magnus [Unit of Molecular Pathology, Department of Genetics and Pathology, Uppsala University (Sweden); Anniko, Matti [Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Tolmachev, Vladimir [Unit of Biomedical Radiation Sciences, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, S-751 85 Uppsala (Sweden)

    2011-01-15

    Aim: The monoclonal antibody cetuximab, targeting the epidermal growth factor receptor (EGFR), is a promising molecular targeting agent to be used in combination with radiation for anticancer therapy. In this study, effects of cetuximab in combination with alpha-emitting radioimmunotherapy (RIT) in a panel of cultured human squamous cell carcinomas (SCCs) were assessed. Methods: SCC cell lines were characterized and treated with cetuximab in combination with anti-CD44v6 RIT using the astatinated chimeric monoclonal antibody U36 ({sup 211}At-cMAb U36). Effects on {sup 211}At-cMAb U36 uptake, internalization and cell proliferation were then assessed in SCC cells. Results: Cetuximab in combination with {sup 211}At-cMAb U36 mediated increased growth inhibition compared to RIT or cetuximab alone in two cell lines. However, cetuximab also mediated radioprotective effects compared to RIT alone in two cell lines. The radioprotective effects occurred in the cell lines in which cetuximab clearly inhibited cell growth during radiation exposure. Cetuximab treatment also influenced {sup 211}At-cMAb-U36 uptake and internalization, suggesting interactions between CD44v6 and EGFR. Conclusions: Results from this study demonstrate the vast importance of further clarifying the mechanisms of cetuximab and radiation response, and the relationship between EGFR and suitable RIT targets. This is important not only in order to avoid potential radioprotective effects, but also in order to find and utilize potential synergistic effects from these combinations.

  6. 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

  7. Preparation of 211At-labeled humanized anti-Tac using 211At produced in disposable internal and external bismuth targets

    International Nuclear Information System (INIS)

    These studies describe the production and purification of 211At as well as the procedure for labeling humanized anti-Tac, the antibody to the α-chain of the IL-2 receptor (IL-2Rα), which has been shown to be a useful target for immunotherapy. The optimized protocol combines the advantages of the two-stage dry distillation procedure with the astatination of trialkylstannyl substances as labeling compounds for proteins. The 211At was produced by bombarding either an external or a recently developed disposable internal bismuth target with α-particles from a Cyclotron Corporation CS-30 cyclotron. The 211At was found to contain less than 0.01% 210At. The production rate for the external target was 0.15 mCi ± 0.056 μA-1 h-1 (n = 9) (5.55 MBq μA-1 h-1). The production rate for the internal target was 0.44 ± 0.14 mCi μA-1 h-1 (n = 16) (16.28 MBq μA-1 h-1)

  8. 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.)

  9. Targeting disseminated melanoma with radiolabelled methylene blue. Comparative bio-distribution studies in man and animals

    International Nuclear Information System (INIS)

    Targeted radiotherapy for pigmented melanoma with 3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with Astatine-211 (211At; α-particle emitter) proved to be very effective in animal model systems. Since the results justified an introduction of the treatment to the clinic, the aim of the bio-distribution studies using [123I]-MTB and [131I]-MTB in patients was to confirm selectiveness of radiolabelled MTB uptake in melanoma lesions. The investigations were carried out using planar and SPECT (single photon emission computed tomography) γ-cameras. A stable uptake of radioiodinated MTB was found in pigmented melanomas in man, with tumour/surrounding tissue and tumour/blood ratio amounting to 9 at 19 h after a single i.v. injection. A time-dependent kinetics of radioiodinated MTB distribution was similar to that observed in human melanoma-bearing athymic mice. Blood radioactivity decreased by about 90% during the first 2.5 min after i.v. injection of the compound (T1/2biol = 0.58 min). Its retention time in various organs was either the same or very similar to that characteristic of the blood. A rapid uptake of radioiodinated MTB in the liver and kidneys confirmed the importance of these organs in excreting the compound: 25-30% of the radioactivity administered was expelled with urine over the first 24 h after the injection. There was no obvious retention of radioiodinated MTB in the brain over the observation period and in the eyes for at least the first 14 h. (orig.)

  10. 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

  11. 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

  12. The role of alpha therapy for local and systemic treatment of cancer

    International Nuclear Information System (INIS)

    Major problems in the management of cancer relate to the inability to control some primary lesions, e.g. glioblastoma multiforme (GBM), and the inability to deal with metastatic cancer arising from malignant cancers such as melanoma, breast and other cancers. Binary alpha therapy using neutron capture in boron-10 offers the potential for improved prognosis for high grade brain tumours such as GBM and melanoma metastases to the brain. Metastatic cancer proceeds through a number of quite separate stages in the development of lethal disease, i e. cells in transit, preangiogenic lesions, subclinical and clinical lesions. Early stages offer the potential for control if targeted alpha therapy is applied. However, the dose must be localised to the cancer cell and this requirement rules out beta-emitting radionuclides, which are more suited for clinical lesions. Alpha-emitting radionuclides are the most appropriate toxins, as their efficacy depends on the linear energy transfer (LET) and range of the alpha particles. After matching the cancer stage, radiolabel and carrier, we find that 149Tb is the radionuclide of choice for systemic therapy in all aspects except production. The production of 149Tb in μCi (kBq) quantities has been achieved using the heavy ion reaction at the ANU tandem accelerator at Canberra and in multi-mCi (MBq) quantities using the spallation reaction in combination with on-line isotope separation technology of ISOLDE at CERN. Terbium is ideally suited for chelation to monoclonal antibodies to produce stable radio-immunoconjugates (RIC). Astatine-211 is a halide and has potential for the elimination of early stage melanoma metastases as At-MTB. However, the availability of the alpha generators 228Th-212Bi and 225Ac-213Bi facilitates the use of Bi-RIC in clinical trials for acute myeloid leukaemia and cystic glioma. Alpha therapy has the potential to control refractory cancers when treated at the minimum residual disease stage. Pre-clinical and

  13. 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)

  14. 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

  15. Radiostatine and radioiodine uptake characterization in sodium iodine symporter-expressing cell lines

    International Nuclear Information System (INIS)

    Full text: The sodium iodide symporter (NIS) has been recognized as an attractive target for cancer gene therapy. Here we investigated NIS-mediated transport of the high LET α-emitter astatine, 211At, in comparison to radioiodine. A constitutive expression vector harbouring the human NIS cDNA was used in combination with reporter gene vectors for transient transfection of 13 different human cancer cell lines. Radioiodine uptake was measured as well as transfection efficiencies. Six stable NIS-expressing cell lines (3 derived from thyroid carcinomas, 2 colon carcinoma, 1 glioblastoma) were generated by antibiotic selection. NIS expression was monitored by immunohistochemistry and RT-PCR. Subsequently the radioastatine and radioiodine uptake characteristics of genetically modified cells were studied in comparison to the respective control cells. After xenotransplantation in nude mice in vivo tumor imaging by scintigraphy and biodistribution studies following organ removal were performed. Transient transfection of NIS cDNA led to high specific sodium perchlorate-sensitive radioiodine uptake in NIS-expressing cells that roughly correlates to transfection efficiencies. Similarly, stable NIS-expressing cell lines were able to concentrate high levels of radioiodine and in addition showed comparable transport capacity for radioastatine. Accumulation of 211At was inhibited by sodium perchlorate like iodide uptake and displayed dependency an extracellular Na+- and I--ions as well. Compared to wash-out experiments in cell culture the effective half life of radioiodine and radioastatine in vivo was significantly prolonged. Preliminary dose calculations by MIRD concepts indicated higher tumor radiation doses for 211At compared to 131I. Tumor cells of different origins transfected with the NIS-expression vector specifically and significantly take-up radioiodine and radioastatine in vitro and in vivo. The data provide direct evidence that the NIS efficiently transports the high

  16. Systematics of Alpha-Radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Perlman, I.; Ghiorso, A.; Seaborg, G.T.

    1949-09-12

    Correlations of alpha-decay energies in terms of mass number and atomic number have been made for all of the alpha-emitting species now numbering over 100. For each element isotopes show increase in alpha-energy with decrease in mass number except in the region of 126 neutrons where there is an explainable reversal. This reversal has the effect of creating a region of relatively low alpha-energy and long half-life at low mass numbers for such elements as astatine, emanation, francium, and possibly higher elements as had been noted already for bismuth and polonium. Methods and examples of using alpha-decay data to define the energy surface in the heavy element region are discussed. The regularities in alpha-decay are used for predictions of nuclear properties including prediction of the beta-stable nuclides among the heavy elements. The half-life vs. energy correlations show that the even-even nuclides conform well with existing alpha-decay theory, but all nuclear types with odd nucleons show prohibited decay. The reason for this prohibition is not found in spin changes in the alpha-emission but in the assembly of the components of the alpha particle, and this theory is discussed further in terms of observations made on nuclides having two or more alpha-groups. Using most of the even-even nuclei to define 'normal nuclear radius' calculations are now able to show the shrinkage in the regions of lead and of 126 neutrons to amount to about 10%. The much greater change in 'effective radius' for bismuth isotopes can be dissociated into the effects of odd nucleons superimposed on the actual decrease in nuclear radius. The simple expression r = 1.48 A{sup 1/3} {center_dot} 10{sup -13} cm seems to fit the data for the even-even nuclei outside of the region of 126 neutrons better than more complex functions.

  17. 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.

  18. Alpha particle emitters in cancer therapy: establishing the rationale and overcoming the difficulties

    International Nuclear Information System (INIS)

    Full text: Once a tumor has metastasized, the possibility of cure is significantly diminished, if not excluded. Since metastatic spread arises due to the release of single tumor cells or tumor cell clusters, treatment regimens following an overt metastasis must include agents that eradicate individual tumor cells and cell clusters or that prevent their dissemination. Alpha particles may be highly effective in eradicating rapidly accessible disease. The effectiveness of alpha particles arises because the amount of energy deposited per unit distance traveled (linear energy transfer or LET) is approximately 400 times greater than that of beta particles (80 keV/μm vs. 0.2 keV/μm). Each traversal of an alpha particle through a cell nucleus results in a very highly ionizing track. Cell survival studies have shown that alpha-particle killing is independent of oxygenation state or cell-cycle during irradiation and that as few as 1 to 6 tracks across the nucleus may result in cell death. Most studies with alpha-particle emitting radionuclides for therapy have examined either bismuth-212 or astatine-211. Both radionuclides are short-lived with 61 minute and 7.2 hour half-lives, respectively, yielding intermediates with 3-minute and 32 year half-lives, respectively. Both emit alpha particles whose range is 40 to 80 μm. Alpha-particle emitting radionuclides have been attached to antibodies against tumor cell associated antigen. Antibodies have been the most widely used vehicle for delivery of alpha particles due to their specificity. Bismuth-212 has demonstrated a significant curative potential with minimal toxicity. In an ascites tumor mouse model, specific targeting and 80% cure following injection of Bi-212-labeled antibody has been observed (Macklis RM et al, Science, 240:1024-1026, 1988). It is important to define the realm of applicability for alpha particle emitting radionuclides. The short half-life of most currently available radionuclides, limits their use to

  19. 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