WorldWideScience

Sample records for astatination

  1. Radiochemistry of astatine

    Energy Technology Data Exchange (ETDEWEB)

    Ruth, T J; Dombsky, M; D' Auria, J M; Ward, T E

    1988-01-01

    This monograph is a review of the literature through 1987 and covers the methods of producing the radioisotopes of astatine and the inorganic, nuclear, and organic chemistry of astatine. The discussion is limited to chemical and physical chemical properties of astatine. The monograph, after the introduction, is divided into chapters titled: production methods, nuclear spectroscopy, chemistry of astatine, separation and isolation (dry and wet), and selected procedures. 209 refs., 15 figs., 7 tabs. (DLC)

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

    Energy Technology Data Exchange (ETDEWEB)

    Fry, C.; Thoennessen, M., E-mail: thoennessen@nscl.msu.edu

    2013-09-15

    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 described. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

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

    CERN Document Server

    Fry, C

    2012-01-01

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

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

    Science.gov (United States)

    Fry, C.; Thoennessen, M.

    2013-09-01

    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 described. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  5. Delayed and In-beam Spectroscopy on Francium and Astatine Nuclei at the Proton Drip Line

    Energy Technology Data Exchange (ETDEWEB)

    Uusitalo, J.; Jakobsson, U. [Department of Physics, University of Jyvaeskylae (Finland); Collaboration: RITU-Gamma Gollaboration

    2011-11-30

    Delayed and in-beam spectroscopy on francium and astatine nuclei at and beyond the proton drip line has been performed. In neutron deficient astatine nuclei a shift to deformed shapes as a function of decreasing neutron has been obtained. In neutron deficient francium isotope the same shift is evident.

  6. Delayed and In-beam Spectroscopy on Francium and Astatine Nuclei at the Proton Drip Line

    Science.gov (United States)

    Uusitalo, J.; Jakobsson, U.

    2011-11-01

    Delayed and in-beam spectroscopy on francium and astatine nuclei at and beyond the proton drip line has been performed. In neutron deficient astatine nuclei a shift to deformed shapes as a function of decreasing neutron has been obtained. In neutron deficient francium isotope the same shift is evident.

  7. 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.

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

    Science.gov (United States)

    Rothe, S; Andreyev, A N; 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, Yuri; Köster, U; Lane, J F W; 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 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 ionization threshold. The observed series of Rydberg states enabled the first determination of the ionization potential of the astatine atom, 9.31751(8) eV. New ab initio calculations are 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 superheavy element 117, the heaviest homologue of astatine.

  9. Spectroscopy of low-lying states in neutron-deficient astatine and francium nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Jakobsson, U., E-mail: ulrjak@kth.se; Cederwall, B. [KTH, The Division of Nuclear Physics, AlbaNova University Center, SE-10691 Stockholm (Sweden); Uusitalo, J.; Auranen, K.; Badran, H.; Cox, D. M.; Grahn, T.; Greenlees, P. T.; Julin, R.; Juutinen, S.; Herzáň, A.; Konki, J.; Leino, M.; Mallaburn, M.; Pakarinen, J.; Papadakis, P.; Partanen, J.; Rahkila, P.; Sandzelius, M.; Sarén, J. [University of Jyvaskyla, Department of Physics, P.O. Box 35, FI-40014 University of Jyvaskyla (Finland); and others

    2015-10-15

    Low-lying states in neutron-deficient astatine and francium nuclei have been studied by means of in-beam and delayed spectroscopy. The 13/2{sup +} state has been observed in francium nuclei with a similar down-sloping trend as in neighbouring astatine and bismuth isotopes, as a function of decreasing neutron number. A systematic trend can also now be seen for the 1/2{sup +} state both in astatine and francium nuclei, where the level energy decreases steeply as a function of neutron number when moving further away from the neutron shell closure. This trend is very similar between astatine nuclei and their francium isotones. Moreover, shape coexistence has been observed between the 13/2{sup +} state and the spherical 9/2{sup −} ground state in {sup 203}Fr and {sup 205}Fr.

  10. Spectroscopy of low-lying states in neutron-deficient astatine and francium nuclei

    Science.gov (United States)

    Jakobsson, U.; Uusitalo, J.; Auranen, K.; Badran, H.; Cederwall, B.; Cox, D. M.; Grahn, T.; Greenlees, P. T.; Julin, R.; Juutinen, S.; HerzáÅ, A.; Konki, J.; Leino, M.; Mallaburn, M.; Pakarinen, J.; Papadakis, P.; Partanen, J.; Rahkila, P.; Sandzelius, M.; Sarén, J.; Scholey, C.; Sorri, J.; Stolze, S.

    2015-10-01

    Low-lying states in neutron-deficient astatine and francium nuclei have been studied by means of in-beam and delayed spectroscopy. The 13/2+ state has been observed in francium nuclei with a similar down-sloping trend as in neighbouring astatine and bismuth isotopes, as a function of decreasing neutron number. A systematic trend can also now be seen for the 1/2+ state both in astatine and francium nuclei, where the level energy decreases steeply as a function of neutron number when moving further away from the neutron shell closure. This trend is very similar between astatine nuclei and their francium isotones. Moreover, shape coexistence has been observed between the 13/2+ state and the spherical 9/2- ground state in 203Fr and 205Fr.

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

    DEFF Research Database (Denmark)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom

    2015-01-01

    To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical...

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

    NARCIS (Netherlands)

    Rothe, S.; Andreyev, A. N.; 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, Yuri; Koester, U.; Lane, J. F. W.; 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.; Sjoedin, A. M.; Van den Bergh, P.; Van Duppen, P.; Venhart, M.; Wakabayashi, Y.; Wendt, K. D. A.

    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

  13. 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...

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

    DEFF Research Database (Denmark)

    Aneheim, Emma; Gustafsson, Anna; Albertsson, Per

    2016-01-01

    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 sing...... 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....

  15. Laser photodetachment of radioactive ions: towards the determination of the electronegativity of astatine

    CERN Multimedia

    Rothe, Sebastian; Welander, Jakob Emanuel; Chrysalidis, Katerina; Day Goodacre, Thomas; Fedosseev, Valentine; Fiotakis, Spyridon; Forstner, Oliver; Heinke, Reinhard Matthias; Johnston, Karl; Kron, Tobias; Koester, Ulli; Liu, Yuan; Marsh, Bruce; Ringvall Moberg, Annie; Rossel, Ralf Erik; Seiffert, Christoph; Studer, Dominik; Wendt, Klaus; Hanstorp, Dag

    2017-01-01

    Negatively charged ions are mainly stabilized through the electron correlation effect. A measure of the stability of a negative ion is the electron affinity, which the energy gain by attaching an electron to a neutral atom. This fundamental quantity is, due to the almost general lack of bound excited states, the only atomic property that can be determined with high accuracy for negative ions. We will present the results of the first laser photodetachment studies of radioactive negative ions at CERN-ISOLDE. The photodetachment threshold for the radiogenic iodine isotope 128I was measured successfully, demonstrating the performance of the upgraded GANDALPH experimental beam line. The first detection of photo-detached astatine atoms marks a milestone towards the determination of the EA of this radioactive element.

  16. Complexation study on no-carrier-added astatine with insulin: A candidate radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Lahiri, Susanta [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India)], E-mail: susanta.lahiri@saha.ac.in; Roy, Kamalika [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India); Sen, Souvik [Berhampur Sadar Hospital, Berhampur, Murshidabad 742 101 (India)

    2008-12-15

    No-carrier-added astatine radionuclides produced in the {sup 7}Li-irradiated lead matrix were separated from bulk lead nitrate target by complexing At with insulin, followed by dialysis. The method offers simultaneous separation of At from lead as well as its complexation with insulin. The At-insulin complex might be a potential radiopharmaceutical in the treatment of hepatocellular carcinoma. The stability of At-insulin complex was checked by dialysis against deionized water and Ringer lactate (RL) solution. It has been found that the half-life of At-insulin complex is about {approx}12 h, when dialyzed against deionized water and is only 6 h, when dialyzed against RL solution having the same composition as blood serum. The 6 h half-life of this Insulin-At complex is perfect for killing cancer cells from external cell surfaces as the half-life of internalization of insulin molecule inside the cell is 7-12 h.

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

    CERN Multimedia

    We propose to conduct the first electron affinity (EA) measurements of the two elements astatine (At) and polonium (Po). Collinear photo-detachment spectroscopy will allow us to measure these quantities with an uncertainty limited only by the spectral line width 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 off-line tests by the clear observation of the photo-detachment threshold for stable iodine. This proposal is based on our Letter of Intent I-148.

  18. Adsorption of the astatine species on a gold surface: A relativistic density functional theory study

    Science.gov (United States)

    Demidov, Yuriy; Zaitsevskii, Andréi

    2018-01-01

    We report first-principle based studies of the adsorption interaction of astatine species on a gold surface. These studies are aimed primarily at the support and interpretation of gas chromatographic experiments with superheavy elements, tennessine (Ts, Z = 117), a heavier homologue of At, and possibly its pseudo-homologue nihonium (Nh, Z = 113). We use gold clusters with up to 69 atoms to simulate the adsorption sites and estimate the desorption energies of At & AtOH from a stable gold (1 1 1) surface. To describe the electronic structure of At -Aun and AtOH -Aun complexes, we combine accurate shape-consistent relativistic pseudopotentials and non-collinear two-component relativistic density functional theory. The predicted desorption energies of At and AtOH on gold are 130 ± 10 kJ/mol and 90 ± 10 kJ/mol, respectively. These results confirm the validity of the estimates derived from chromatographic data (147 ± 15 kJ/mol for At, and 100-10+20 kJ/mol for AtOH).

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

    Energy Technology Data Exchange (ETDEWEB)

    MICHAEL R. ZALUTSKY

    2012-08-08

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Rothe, Sebastian

    2012-09-24

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

  1. An all-solid state laser system for the laser ion 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.

  2. 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 [Univ. of Washington, Seattle, WA (United States)

    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

  3. An automated flow system incorporating in-line acid dissolution of bismuth metal from a cyclotron irradiated target assembly for use in the isolation of astatine-211

    Energy Technology Data Exchange (ETDEWEB)

    O’Hara, Matthew J.; Krzysko, Anthony J.; Niver, Cynthia M.; Morrison, Samuel S.; Owsley, Stanley L.; Hamlin, Donald K.; Dorman, Eric F.; Scott Wilbur, D.

    2017-04-01

    Astatine-211 (211At) is a promising cyclotron-produced radionuclide being investigated for use in targeted alpha therapy of blood borne and metastatic cancers, as well as treatment of tumor remnants after surgical resections. The isolation of trace quantities of 211At, produced within several grams of a Bi metal cyclotron target, involves a complex, multi-step procedure: (1) Bi metal dissolution in strong HNO3, (2) distillation of the HNO3 to yield Bi salts containing 211At, (3) dissolution of the salts in strong HCl, (4) solvent extraction of 211At from bismuth salts with diisopropyl ether (DIPE), and (5) back-extraction of 211At from DIPE into NaOH, leading to a purified 211At product. Step (1) has been addressed first to begin the process of automating the onerous 211At isolation process. A computer-controlled Bi target dissolution system has been designed. The system performs in-line dissolution of Bi metal from the target assembly using an enclosed target dissolution block, routing the resulting solubilized 211At/Bi mixture to the subsequent process step. The primary parameters involved in Bi metal solubilization (HNO3 concentration and influent flow rate) were optimized prior to evaluation of the system performance on replicate cyclotron irradiated targets. The results indicate that the system performs reproducibly, having nearly quantitative release of 211At from irradiated targets, with cumulative 211At recoveries that follow a sigmoidal function. The predictable nature of the 211At release profile allows the user to tune the system to meet target processing requirements.

  4. Reagents for astatination of biomolecules. 2. Conjugation of anionic boron cage pendant groups to a protein provides a method for direct labeling that is stable to in vivo deastatination.

    Science.gov (United States)

    Wilbur, D Scott; Chyan, Ming-Kuan; Hamlin, Donald K; Vessella, Robert L; Wedge, Timothy J; Hawthorne, M Frederick

    2007-01-01

    Cancer-targeting biomolecules labeled with 211At must be stable to in vivo deastatination, as control of the 211At distribution is critical due to the highly toxic nature of alpha-particle emission. Unfortunately, no astatinated aryl conjugates have shown in vivo stability toward deastatination when (relatively) rapidly metabolized proteins, such as monoclonal antibody Fab' fragments, are labeled. As a means of increasing the in vivo stability of 211At-labeled proteins, we have been investigating antibody conjugates of boron cage moieties. In this investigation, protein-reactive derivatives containing a nido-carborane (2), a bis-nido-carborane derivative (Venus Flytrap Complex, 3), and four 2-nonahydro-closo-decaborate(2-) derivatives (4-7) were prepared and conjugated with an antibody Fab' fragment such that subsequent astatination and in vivo tissue distributions could be obtained. To aid in determination of stability toward in vivo deastatination, the Fab'-borane conjugates were also labeled with 125I, and that material was coinjected with the 211At-labeled Fab'. For comparison, direct labeling of the Fab' with 125I and 211At was conducted. Direct labeling with Na[125I]I and Chloramine-T gave an 89% radiochemical yield. However, direct labeling of the Fab' with Na[211At]At and Chloramine-T resulted in a yield of Studies to optimize the closo-decaborate(2-) conjugates for protein labeling are underway.

  5. 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.

  6. 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.

  7. Evaluation of Novel Wet Chemistry Separation and Purification Methods to Facilitate Automation of Astatine-­211 Isolation

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, Daniel Scott [Univ. of Washington, Seattle, WA (United States)

    2016-07-19

    This research is a collaborative effort between the research groups of the PIs, Dr. D. Scott Wilbur in the Department of Radiation Oncology at the University of Washington (UW) and Matthew O’Hara at the Pacific Northwest National Laboratory (PNNL). In this report only those studies conducted at UW and the budget information from UW will be reported. A separate progress and financial report will be provided by PNNL. This final report outlines the experiments (Tasks) conducted and results obtained at UW from July 1, 2013 thru June 30, 2016 (2-­year project with 1 year no-­cost extension). The report divides the information on the experiments and results obtained into the 5 specific objectives of the research efforts and the Tasks within those objectives. This format is used so that it is easy to see what has been accomplished in each area. A brief summary of the major findings from the studies is provided below. Summary of Major Findings from Research/Training Activities at UW: Anion and cation exchange columns did not provide adequate 211At capture and/or extraction results under conditions studied to warrant further evaluation; PEG-­Merrifield resins containing mPEG350, mPEG750, mPEG2000 and mPEG5000 were synthesized and evaluated; All of the mPEG resins with different sized mPEG moieties conjugated gave similar 211At capture (>95%) from 8M HCl solutions and release with conc. NH4OH (~50-­80%), but very low quantities were released when NaOH was used as an eluent; Capture and release of 211At when loading [211At]astatate appeared to be similar to that of [211At]astatide on PEG columns, but further studies need to be conducted to confirm that; Capture of 211At on PEG columns was lower (e.g. 80-­90%) from solutions of 8M HNO3, but higher capture rates (e.g. 99%) can be obtained when 10M HNO3 is mixed with an equal quantity of 8M HCl; Addition of reductants to the 211At solutions did not appear to change the percent capture, but may have an effect on the % extracted; There was some indication that the PEG-­Merrifield resins could be saturated (perhaps with Bi) resulting in lower capture percentages, but more studies need to be done to confirm that; A target dissolution chamber, designed and built at PNNL, works well with syringe pumps so it can be used in an automated system; Preliminary semi-­automated 211At isolation studies have been conducted with full-scale target dissolution and 211At isolation using a PEG column on the Hamilton automated system gave low overall recoveries, but HNO3 was used (rather than HCl) for loading the 211At and flow rates were not optimized; Results obtained using PEG columns are high enough to warrant further development on a fully automated system; Results obtained also indicate that additional studies are warranted to evaluate other types of columns for 211At separation from bismuth, which allow use of HNO3/HCl mixtures for loading and NaOH for eluting 211At. Such a column could greatly simplify the overall isolation process and make it easier to automate.

  8. 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.

  9. Derivation of Soil Screening Guidelines for Gross Alpha/Beta Radioactivity for United States Air Force Deployment Sites

    Science.gov (United States)

    2007-04-19

    the emission of 7 alpha particles and 4 beta particles. Three radionuclides ( francium -223, astatine-215, and polonium-211) are not listed below...no no Uranium-233 159,200 y alpha yes no Thorium-229 7,300 y alpha yes no Radium-225 14.9 d beta no no Actinium-225 10.0 d alpha no no Francium

  10. δ37Cl : the geochemistry of chlorine isotopes

    NARCIS (Netherlands)

    Eggenkamp, H.G.M.

    1994-01-01

    In this thesis the geochemistry of the stable isotopes of chlorine will be examined. Chlorine is one of the halogens, the seventh group in the periodic system of elements. This group consists of five elements, fluorine, chlorine, bromine, iodine, and astatine.

  11. δ³⁷Cl : the geochemistry of chlorine isotopes

    NARCIS (Netherlands)

    Eggenkamp, H.G.M.

    1994-01-01

    In this thesis the geochemistry of the stable isotopes of chlorine will be examined. Chlorine is one of the halogens, the seventh group in the periodic system of elements. This group consists of five elements, fluorine, chlorine, bromine, iodine, and astatine. This thesis presents the first chlorine

  12. 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.

  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. Production cross section of At radionuclides from 7Li+natPb and 9Be+natTl reactions

    Science.gov (United States)

    Maiti, Moumita; Lahiri, Susanta

    2011-12-01

    Earlier we reported theoretical studies on the probable production of astatine radionuclides from 6,7Li- and 9Be-induced reactions on natural lead and thallium targets, respectively. The production of astatine radionuclides were investigated experimentally with two heavy-ion-induced reactions: 9Be + natTl and 7Li + natPb. Formation cross sections of the evaporation residues, 207,208,209,210At, produced in the (HI,xn) channel, were measured by the stacked-foil technique followed by off-line γ spectrometry at low incident energies (<50 MeV). Measured excitation functions were interpreted in terms of a compound nuclear reaction mechanism using Weisskopf-Ewing and Hauser-Feshbach models. Measured cross-section values are lower than the respective theoretical predictions.

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

    Energy Technology Data Exchange (ETDEWEB)

    Koziorowski, J

    1998-10-01

    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 {sup 211}At and {sup 124}I, 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-[{sup 211}At]astato-2`-deoxyuridine (AUdR) and N-succinimidyl-4-[{sup 211}At]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- [{sup 124}I]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-[{sup 124}I]iodo-2`-deoxyuridine (IUdR) is presented. The closo-dodecaborate anion was evaluated as prosthetic group for

  17. 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...... mechanism as (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...

  18. 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.

  19. 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...

  20. Nuclear and in-source laser spectroscopy with the ISAC yield station

    Energy Technology Data Exchange (ETDEWEB)

    Kunz, Peter, E-mail: pkunz@triumf.ca; Bricault, Pierre; Dombsky, Marik; Lassen, Jens; Teigelhöfer, Andrea; Heggen, Henning [TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia V6T 2A3 (Canada); Andreoiu, Corina; Wong, Fiona [Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6 (Canada)

    2014-05-15

    A new decay station has been built for the ISAC facility at TRIUMF for the rapid and reliable characterization of radioactive ion beam (RIB) compositions and intensities with the capability of simultaneously collecting α, β, and γ decay data from RIB with intensities between a few and ≈10{sup 11} ions per second. It features user-friendly control, data acquisition, and analysis software. The analysis of individual decay time structures allows the unambiguous assignment of α and γ lines even with substantial isobaric contamination present. The capability for accurate half-life measurements is demonstrated with the example of {sup 46}K. The coupling of the yield station to the laser ion source, TRILIS, allows the correlation of radiometric data with automated laser frequency scans. First results of in-source laser spectroscopy measurements on astatine are discussed.

  1. Nuclear and in-source laser spectroscopy with the ISAC yield station.

    Science.gov (United States)

    Kunz, Peter; Andreoiu, Corina; Bricault, Pierre; Dombsky, Marik; Lassen, Jens; Teigelhöfer, Andrea; Heggen, Henning; Wong, Fiona

    2014-05-01

    A new decay station has been built for the ISAC facility at TRIUMF for the rapid and reliable characterization of radioactive ion beam (RIB) compositions and intensities with the capability of simultaneously collecting α, β, and γ decay data from RIB with intensities between a few and ≈10(11) ions per second. It features user-friendly control, data acquisition, and analysis software. The analysis of individual decay time structures allows the unambiguous assignment of α and γ lines even with substantial isobaric contamination present. The capability for accurate half-life measurements is demonstrated with the example of (46)K. The coupling of the yield station to the laser ion source, TRILIS, allows the correlation of radiometric data with automated laser frequency scans. First results of in-source laser spectroscopy measurements on astatine are discussed.

  2. Radiopharmaceutical chemistry of targeted radiotherapeutics, part 4: Strategies for211At labeling at high activities and radiation doses of211At α-particles.

    Science.gov (United States)

    Pozzi, Oscar R; Zalutsky, Michael R

    2017-03-01

    Alpha particles are radiation of high energy and short range, properties that can lead to radiolysis-mediated complications in labeling chemistry at the high radioactivity levels required for clinical application. In previous papers in this series, we have shown that radiation dose has a profound effect on the astatine species that are present in the labeling reaction and their suitability for the synthesis of N-succinimidyl 3-[ 211 At]astatobenzoate. The purpose of this study was to evaluate the effects of adding N-chlorosuccinimide (NCS) to the methanol solution used for initial isolation of 211 At after distillation, a process referred to as 211 At stabilization, on 211 At chemistry after exposure to high radiation doses. High performance liquid chromatography was used to evaluate the distribution of 211 At species present in methanol in the 500-65,000Gy radiation dose range and the synthesis of SAB from N-succinimidyl 3-(tri-n-butylstannyl)benzoate in the 500-120,000Gy radiation dose range using different 211 At timeactivity combinations under conditions with/without 211 At stabilization. In the absence of NCS stabilization, a reduced form of astatine, At(2), increased with increasing radiation dose, accounting for about half the total activity by about 15,000Gy, while with stabilization, At(2) accounted for 60,000Gy. SAB yields without stabilization rapidly declined with increasing dose, falling to ~20% at about 5000Gy while with stabilization, yields >80% were obtained with 211 At solutions stored for more than 23h and receiving radiation doses >100,000Gy. Adding NCS to the methanol solution used for initial isolation of 211 At is a promising strategy for countering the deleterious effects of radiolysis on 211 At chemistry. This strategy could facilitate the ability to perform 211 At labeling at sites remote from its production and at the high activity levels required for clinical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Alpha particle emitters in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.

    1989-09-01

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

  4. α decay of the very neutron-deficient isotopes 197-199Fr

    Science.gov (United States)

    Kalaninová, Z.; Andreyev, A. N.; Antalic, S.; Heßberger, F. P.; Ackermann, D.; Andel, B.; Drummond, M. C.; Hofmann, S.; Huyse, M.; Kindler, B.; Lane, J. F. W.; Liberati, V.; Lommel, B.; Page, R. D.; Rapisarda, E.; Sandhu, K.; Šáro, Š.; Thornthwaite, A.; Van Duppen, P.

    2013-04-01

    Decay properties of the very neutron-deficient isotopes 197-199Fr were studied at the velocity filter Separator for Heavy Ion reaction Products (SHIP) at GSI in Darmstadt. The isotopes were produced in the 2n-4n evaporation channels of the fusion-evaporation reaction 60Ni+141Pr → 201Fr*. Improved α-decay properties of 199Fr were determined and the possible existence of two α-decaying states in this nucleus is discussed. For the isotope 198Fr a broad α-decay energy distribution was detected in the range of (7470-7930) keV and two α-decaying states were observed with half-lives of 1.1(7) and 15(3) ms. The new isotope 197Fr was identified based on the observation of one α-decay chain yielding Eα=7728(15) keV and T1/2=0.6-0.3+3.0 ms. The systematics of reduced α-decay widths are presented for neutron-deficient francium, radon, and astatine isotopes.

  5. Nuclear Data Evaluation for Mass Chain A=217:Odd-Proton Nuclei.

    Directory of Open Access Journals (Sweden)

    Sherif S Nafee

    Full Text Available Thallium (81(217Tl, Bismuth (83(217Bi, Astatine (85(217At, Francium (87(217Fr, Actinium (89(217Ac and Protactinium (91(217Pa are of odd-proton numbers among the mass chain A = 217. In the present work, the half-lives and gamma transitions for the six nuclei have been studied and adopted based on the recently published interactions or unevaluated nuclear data sets XUNDL. The Q (α has been updated based on the recent published work of the Atomic Mass Evaluation AME2012 as well. Moreover, the total conversion electrons as well as the K-Shell to L-Shell, L-Shell to M-Shell and L-Shell to N-Shell Conversion Electron Ratios have been calculated using BrIcc code v2.3. An updated skeleton decay scheme for each of the above nuclei has been presented here. The decay hindrance factors (HF calculated using the ALPHAD program, which is available from Brookhaven National Laboratory's website, have been calculated for the α- decay data sets for (221Fr-, (221Ac- and (221Pa-α-decays.

  6. Nuclear Data Evaluation for Mass Chain A=217:Odd-Proton Nuclei.

    Science.gov (United States)

    Nafee, Sherif S; Shaheen, Salem A; Al-Ramady, Amir M

    2016-01-01

    Thallium (81(217)Tl, Bismuth (83(217)Bi), Astatine (85(217)At), Francium (87(217)Fr), Actinium (89(217)Ac) and Protactinium (91(217)Pa) are of odd-proton numbers among the mass chain A = 217. In the present work, the half-lives and gamma transitions for the six nuclei have been studied and adopted based on the recently published interactions or unevaluated nuclear data sets XUNDL. The Q (α) has been updated based on the recent published work of the Atomic Mass Evaluation AME2012 as well. Moreover, the total conversion electrons as well as the K-Shell to L-Shell, L-Shell to M-Shell and L-Shell to N-Shell Conversion Electron Ratios have been calculated using BrIcc code v2.3. An updated skeleton decay scheme for each of the above nuclei has been presented here. The decay hindrance factors (HF) calculated using the ALPHAD program, which is available from Brookhaven National Laboratory's website, have been calculated for the α- decay data sets for (221)Fr-, (221)Ac- and (221)Pa-α-decays.

  7. On the theory of time dilation in chemical kinetics

    Science.gov (United States)

    Baig, Mirza Wasif

    2017-10-01

    The rates of chemical reactions are not absolute but their magnitude depends upon the relative speeds of the moving observers. This has been proved by unifying basic theories of chemical kinetics, which are transition state theory, collision theory, RRKM and Marcus theory, with the special theory of relativity. Boltzmann constant and energy spacing between permitted quantum levels of molecules are quantum mechanically proved to be Lorentz variant. The relativistic statistical thermodynamics has been developed to explain quasi-equilibrium existing between reactants and activated complex. The newly formulated Lorentz transformation of the rate constant from Arrhenius equation, of the collision frequency and of the Eyring and Marcus equations renders the rate of reaction to be Lorentz variant. For a moving observer moving at fractions of the speed of light along the reaction coordinate, the transition state possess less kinetic energy to sweep translation over it. This results in the slower transformation of reactants into products and in a stretched time frame for the chemical reaction to complete. Lorentz transformation of the half-life equation explains time dilation of the half-life period of chemical reactions and proves special theory of relativity and presents theory in accord with each other. To demonstrate the effectiveness of the present theory, the enzymatic reaction of methylamine dehydrogenase and radioactive disintegration of Astatine into Bismuth are considered as numerical examples.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jaszczak, R.J.

    1993-08-20

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

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

    Science.gov (United States)

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

    2013-12-01

    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 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.

  10. 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. \\...

  11. Tumor Immunotargeting Using Innovative Radionuclides

    Directory of Open Access Journals (Sweden)

    Françoise Kraeber-Bodéré

    2015-02-01

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

  12. Evaluating 99mTc Auger electrons for targeted tumor radiotherapy by computational methods.

    Science.gov (United States)

    Tavares, Adriana Alexandre S; Tavares, João Manuel R S

    2010-07-01

    Technetium-99m (99mTc) has been widely used as an imaging agent but only recently has been considered for therapeutic applications. This study aims to analyze the potential use of 99mTc Auger electrons for targeted tumor radiotherapy by evaluating the DNA damage and its probability of correct repair and by studying the cellular kinetics, following 99mTc Auger electron irradiation in comparison to iodine-131 (131I) beta minus particles and astatine-211 (211At) alpha particle irradiation. Computational models were used to estimate the yield of DNA damage (fast Monte Carlo damage algorithm), the probability of correct repair (Monte Carlo excision repair algorithm), and cell kinetic effects (virtual cell radiobiology algorithm) after irradiation with the selected particles. The results obtained with the algorithms used suggested that 99mTc CKMMX (all M-shell Coster-Kroning--CK--and super-CK transitions) electrons and Auger MXY (all M-shell Auger transitions) have a therapeutic potential comparable to high linear energy transfer 211At alpha particles and higher than 131I beta minus particles. All the other 99mTc electrons had a therapeutic potential similar to 131I beta minus particles. 99mTc CKMMX electrons and Auger MXY presented a higher probability to induce apoptosis than 131I beta minus particles and a probability similar to 211At alpha particles. Based on the results here, 99mTc CKMMX electrons and Auger MXY are useful electrons for targeted tumor radiotherapy.

  13. Radiobromination of humanized anti-HER2 monoclonal antibody trastuzumab using N-succinimidyl 5-bromo-3-pyridinecarboxylate, a potential label for immunoPET

    Energy Technology Data Exchange (ETDEWEB)

    Mume, Eskender [Organic Chemistry, Department of Chemistry, Uppsala University, S-751 24 Uppsala (Sweden); Orlova, Anna [Affibody AB, S-161 02 Bromma (Sweden); Malmstroem, Per-Uno [Division of Urology, Department of Surgical Sciences, Uppsala University, S-751 85 Uppsala (Sweden); Lundqvist, Hans [Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala (Sweden); Sjoeberg, Stefan [Organic Chemistry, Department of Chemistry, Uppsala University, S-751 24 Uppsala (Sweden); Tolmachev, Vladimir [Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, S-751 85 Uppsala (Sweden)]. E-mail: vladimir.tolmachev@bms.uu.se

    2005-08-01

    Combining the specificity of radioimmunoscintigraphy and the high sensitivity of PET in an in vivo detection technique could improve the quality of nuclear diagnostics. Positron-emitting nuclide {sup 76}Br (T {sub 1/2}=16.2 h) might be a possible candidate for labeling monoclonal antibodies (mAbs) and their fragments, provided that the appropriate labeling chemistry has been established. For internalizing antibodies, such as the humanized anti-HER2 monoclonal antibody, trastuzumab, radiobromine label should be residualizing, i.e., ensuring that radiocatabolites are trapped intracellularly after the proteolytic degradation of antibody. This study evaluated the chemistry of indirect radiobromination of trastuzumab using N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate. Literature data indicated that the use of this method provided residualizing properties for iodine and astatine labels on some antibodies. An optimized 'one-pot' procedure produced an overall labeling efficiency of 45.5{+-}1.2% over 15 min. The bromine label was stable under physiological and denaturing conditions. The labeled trastuzumab retained its capacity to bind specifically to HER2-expressing SKOV-3 ovarian carcinoma cells in vitro (immunoreactivity more than 75%). However, in vitro cell test did not demonstrate that the radiobromination of trastuzumab using N-succinimidyl 5-bromo-3-pyridinecarboxylate improves cellular retention of radioactivity in comparison with the use of N-succinimidyl 4-bromobenzoate.

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

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.; Zalutsky, M.; Bloomer, W.

    1981-01-01

    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 /sup 131/I 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, /sup 211/At 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 /sup 211/At-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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-01

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

  16. 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 ...

  17. Optimizing MIBG therapy of neuroendocrine tumors: preclinical evidence of dose maximization and synergy

    Energy Technology Data Exchange (ETDEWEB)

    Mairs, Rob J. [Department of Radiation Oncology, University of Glasgow, Glasgow (United Kingdom)], E-mail: r.mairs@beatson.gla.ac.uk; Boyd, Marie [Department of Radiation Oncology, University of Glasgow, Glasgow (United Kingdom)

    2008-08-15

    [{sup 131}I]meta-Iodobenzylguanidine ([{sup 131}I]MIBG) has been used for the therapy of tumors of neuroectodermal origin since the 1980s. Its role in the management of these malignancies remains controversial because of the large variation in response rates. Appreciation of the mode of conveyance of [{sup 131}I]MIBG via the noradrenaline transporter into malignant cells and of factors that influence the activity of the uptake mechanism has indicated various ways in which the effectiveness of this type of targeted radiotherapy may be improved. Experimental observations indicate that radiolabeling of MIBG to high specific activity reduced the amount of cold competitor, thereby increasing tumor dose and minimizing pressor effects. We observed supra-additive tumor cell kill and inhibition of tumor growth following combined topotecan and [{sup 131}I]MIBG treatment. The improved efficacy is related to topotecan's increased disruption of DNA repair. Radiation damage to targeted tumors may also be enhanced by the use of the {alpha}-particle emitter [{sup 211}At]astatine rather than {sup 131}I as radiolabel. Furthermore, recent experimental findings indicate that [{sup 123}I]MIBG may have therapeutic potential over and above its utility as an imaging agent. It has recently been demonstrated that potent cytotoxic bystander effects were induced by the intracellular concentration of [{sup 131}I]MIBG, [{sup 123}I]MIBG or meta-[{sup 211}At]astatobenzylguanidine. Identification of the nature of bystander factors could be exploited to maximize the specificity and potency of MIBG-targeted radiotherapy. By employing a range of strategies, there are good prospects for the improvement of the [{sup 131}I]MIBG therapy of neuroectodermal tumors.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bourgeois, M

    2007-05-15

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

  19. Locoregional therapy with α-emitting trastuzumab against peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice.

    Science.gov (United States)

    Li, Huizi Keiko; Morokoshi, Yukie; Nagatsu, Kotaro; Kamada, Tadashi; Hasegawa, Sumitaka

    2017-08-01

    Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 ((211) At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that (211) At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test α-particle radioimmunotherapy with (211) At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of (211) At-trastuzumab (1 MBq) was a more efficient means of delivery of (211) At into metastatic tumors than i.v. injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of (211) At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA double-strand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered (211) At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with (211) At-trastuzumab may offer a new treatment option for HER2-positive PMGC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  20. 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

  1. 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

  2. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Allen, B.J. [St George Hospital, Kogarah, NSW (Australia)

    1998-03-01

    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 {sup 149}Tb is the radionuclide of choice for systemic therapy in all aspects except production. The production of {sup 149}Tb in {mu}Ci (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 {sup 228}Th-{sup 212}Bi and {sup 225}Ac-{sup 213}Bi 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

  4. 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.