WorldWideScience

Sample records for astatine

  1. Astatine-211: production and availability.

    Science.gov (United States)

    Zalutsky, Michael R; Pruszynski, Marek

    2011-07-01

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

  2. 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.

  3. 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.

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

    DEFF Research Database (Denmark)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom

    2015-01-01

    and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting......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...

  5. 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.

    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 behaviou

  6. 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.

  7. 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.

  8. Ionization potentials, electron affinities, resonance excitation energies, oscillator strengths, and ionic radii of element Uus (Z = 117) and astatine.

    Science.gov (United States)

    Chang, Zhiwei; Li, Jiguang; Dong, Chenzhong

    2010-12-30

    Multiconfiguration Dirac-Fock (MCDF) method was employed to calculate the first five ionization potentials, electron affinities, resonance excitation energies, oscillator strengths, and radii for the element Uus and its homologue At. Main valence correlation effects were taken into account. The Breit interaction and QED effects were also estimated. The uncertainties of calculated IPs, EAs, and IR for Uus and At were reduced through an extrapolation procedure. The good consistency with available experimental and other theoretical values demonstrates the validity of the present results. These theoretical data therefore can be used to predict some unknown physicochemical properties of element Uus, Astatine, and their compounds.

  9. 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

  10. 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.

  11. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Claesson, Kristina

    2011-05-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, D., Scott

    2011-12-14

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

  14. 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.

  15. Preparation of Rh[16aneS4-diol](211)At and Ir[16aneS4-diol](211)At complexes as potential precursors for astatine radiopharmaceuticals. Part I: Synthesis.

    Science.gov (United States)

    Pruszyński, Marek; Bilewicz, Aleksander; Zalutsky, Michael R

    2008-04-01

    The goal of this study was to evaluate a new approach that can be applied for labeling biomolecules with (211)At. Many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking different (211)At labeling strategies. The approach evaluated in this study was to attach astatide anions to soft metal cations, which are also complexed by a bifunctional ligand. Ultimately, this complex could in principle be subsequently conjugated to a biomolecule with the proper selection of ligand functionality. We report here the attachment of (211)At(-) and *I(-) (*I = (131)I or (125)I) anions to the soft metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16aneS4-diol) ligand. Radioactive *I(-) anions were used for preliminary studies directed at the optimization of reaction conditions and to provide a baseline for comparison of results with (211)At. Four complexes Rh[16aneS4-diol]*I/(211)At and Ir[16aneS4-diol]*I/(211)At were synthesized in high yield in a one-step procedure, and the products were characterized mainly by paper electrophoresis and reversed-phase HPLC. The influences of time and temperature of heating and concentrations of metal cations and sulfur ligand 16aneS4-diol, as well as pH on the reaction yields were determined. Yields of about 80% were obtained when the quantities of Rh(III) or Ir(III) cations and 16aneS4-diol ligand in the solutions were 62.5 nmol and 250 nmol, respectively, and the pH ranged 3.0-4.0. Syntheses required heating for 1-1.5 h at 75-80 degrees C. The influence of microwave heating on the time and completeness of the complexation reaction was evaluated and compared with the conventional method of heating in an oil bath. Microwave synthesis accelerates reactions significantly. With microwave heating, yields of about 75% for Rh[16aneS4-diol](131)I and Ir[16aneS4-diol](131)I complexes were obtained after only 20 min exposure of the reaction mixtures to

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 10 CFR Appendix C to Part 20 - Quantities 1 of Licensed Material Requiring Labeling

    Science.gov (United States)

    2010-01-01

    ... Polonium-205 1,000 Polonium-207 1,000 Polonium-210 0.1 Astatine-207 100 Astatine-211 10 Radon-220 1 Radon-222 1 Francium-222 100 Francium-223 100 Radium-223 0.1 Radium-224 0.1 Radium-225 0.1 Radium-226...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. Successful radioimmunotherapy of established syngeneic rat colon carcinoma with 211At-mAb

    DEFF Research Database (Denmark)

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

    2013-01-01

    Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with α-emitting radionuclides such as astatine-211 (211At). Radioimmunotherapy utilizing α-particle emitting radionuclides is considered...... colon carcinoma with tumor diameters of approximately 10 mm....

  3. $\\beta$-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.

  4. Sp ectroscopy of Low-lying States in Odd-Z Odd-A Nuclei Beyond Lead

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

    Low-lying states in odd-Z odd-mass nuclei at the proton drip-line beyond lead have recently been studied through fusion-evaporation reactions using a gas-filled recoil separator. Isomeric 1/2+ and 13/2+ states have been observed in odd-mass astatine and francium nuclei. The systematic behaviour of the level energies of these states have been studied and a similarity between the 1/2+ state in astatine and francium has been found. Furthermore, the 13/2+ state has been observed in the francium nuclei with an oblate behaviour suggesting a coupling of the i13/2 proton to the 2p−2h intruder excitation.

  5. Two-component relativistic density-functional calculations of the dimers of the halogens from bromine through element 117 using effective core potential and all-electron methods.

    Science.gov (United States)

    Mitin, Alexander V; van Wüllen, Christoph

    2006-02-14

    A two-component quasirelativistic Hamiltonian based on spin-dependent effective core potentials is used to calculate ionization energies and electron affinities of the heavy halogen atom bromine through the superheavy element 117 (eka-astatine) as well as spectroscopic constants of the homonuclear dimers of these atoms. We describe a two-component Hartree-Fock and density-functional program that treats spin-orbit coupling self-consistently within the orbital optimization procedure. A comparison with results from high-order Douglas-Kroll calculations--for the superheavy systems also with zeroth-order regular approximation and four-component Dirac results--demonstrates the validity of the pseudopotential approximation. The density-functional (but not the Hartree-Fock) results show very satisfactory agreement with theoretical coupled cluster as well as experimental data where available, such that the theoretical results can serve as an estimate for the hitherto unknown properties of astatine, element 117, and their dimers.

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

    CERN Document Server

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

    2003-01-01

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

  7. Is electronegativity a useful descriptor for the pseudo-alkali metal NH4?

    Science.gov (United States)

    Whiteside, Alexander; Xantheas, Sotiris S; Gutowski, Maciej

    2011-11-18

    Molecular ions in the form of "pseudo-atoms" are common structural motifs in chemistry, with properties that are transferrable between different compounds. We have determined one such property--the electronegativity--for the "pseudo-alkali metal" ammonium (NH(4)), and evaluated its reliability as a descriptor versus the electronegativities of the alkali metals. The computed properties of ammonium's binary complexes with astatine and of selected borohydrides confirm the similarity of NH(4) to the alkali metal atoms, although the electronegativity of NH(4) is relatively large in comparison to its cationic radius. We have paid particular attention to the molecular properties of ammonium (angular anisotropy, geometric relaxation and reactivity), which can cause deviations from the behaviour expected of a conceptual "true alkali metal" with this electronegativity. These deviations allow for the discrimination of effects associated with the molecular nature of NH(4).

  8. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, D. Scott

    2011-12-23

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-15

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

  13. Cyclotron production of cesium radionuclides as analogues for francium-221 biodistribution

    Science.gov (United States)

    Finn, R.; McDevitt, M.; Sheh, Y.; Lom, C.; Qiao, J.; Cai, S.; Burnazi, E.; Nacca, A.; Pillarsetty, N.; Jaggi, J.; Scheinberg, D.

    2005-12-01

    In our clinical investigations focussing on improved therapeutic treatment of specific tumors we have concentrated on a targeted therapy approach utilizing designed radiolabeled monoclonal antibodies as the cytotoxic reagent. The physical characteristics of the alpha particle emitting radionuclide bismuth-213 including the short half-life of 45.6 min, has shown promise for the treatment of specific cancers such as leukemias and lymphomas or micrometastatic carcinomas. In an effort to increase the cytocidal effect of the HuM195, a humanized monoclonal antibody carrier to the CD33 antigen expressed on leukemia cells, our focus is directed toward an "internal" nano-generator composed of Ac-225 radionuclide, the parent of the bismuth-213. The actinium-225 radionuclide decays through several short-lived, alpha emitting daughters including francium-221, astatine-217 and bismuth-213. In order to study the biodistribution and the pharmacokinetics of the individual daughter nuclide, francium-221, the cyclotron production and separation of cesium radionuclides, specifically cesium-132, from a natural xenon gas target was undertaken. The choice of cesium as an analogue for francium was predicated upon both elements being in Group 1A alkali metals and cesium radionuclide possesses a sufficient half-life to allow biodistribution studies to be performed. The preliminary experimental results of this investigation are presented.

  14. 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.

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

    CERN Document Server

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

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

  16. Metalloids, soil chemistry and the environment.

    Science.gov (United States)

    Lombi, Enzo; Holm, Peter E

    2010-01-01

    This chapter reviews physical chemical properties, origin and use ofmetalloids and their relevance in the environment. The elements boron (B), silicon (Si), germanium (Ge), arsenic (As), antimony (Sb), tellurium (Te), polonium (Po) and astatine (At) are considered metalloids. Metalloids conduct heat and electricity intermediate between nonmetals and metals and they generally form oxides. The natural abundance ofmetalloids varies from Si being the second most common element in the Earth's crust to At as the rarest of natural elements on Earth. The metalloid elements Ge, Te, Po and At are normally present in trace or ultratrace levels in the environment and as such are not considered of relevance in terms of environmental health. The environmental geochemical processes, factors and parameters controlling the partitioning and the speciation of B, Si, As and Sb are reviewed in relation to the bioavailability of these metalloids. Approaches based on the hypothesis that metal toxicity is related to both the metal-ligand complexation processes and the metal interactions with competing cations at the cell surface (biotic ligand) have so far not been successful for assessing metalloid bioavailability. The chapter concludes that our understanding of metalloids toxicity will improve in the future if, in addition to the points discussed above, surface membrane potentials are considered. This should represent a robust approach to the prediction of metalloid toxicity.

  17. 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.

  18. Glomerular filtration rate after alpha-radioimmunotherapy with 211At-MX35-F(ab')2: a long-term study of renal function in nude mice

    DEFF Research Database (Denmark)

    Back, T.; Haraldsson, B.; Hultborn, R;

    2009-01-01

    and animals bearing subcutaneous xenografts of the human ovarian cancer cell line, OVCAR-3, were used. The animals received approximately 0.4, 0.8, or 1.2 MBq in one, two, or three fractions. The mean absorbed doses to the kidneys ranged from 1.5 to 15 Gy. The renal function was studied by serial GFR...... of the glomerular filtration rate (GFR). The renal toxicity was evaluated at levels close to the dose limit for the bone marrow and well within the range for therapeutic efficacy on tumors. Astatinated MX35-F(ab')(2) monoclonal antibodies were administered intravenously to nude mice. Both non-tumor-bearing animals...... manifested late. Examination of the kidney sections showed histologic changes that were overall subdued. Following alpha-RIT with (211)At-MX35-F(ab')(2) at levels close to the dose limit of severe myelotoxicity, the effects found on renal function were relatively small, with only minor to moderate reductions...

  19. 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.

  20. 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. \\...

  1. 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.

  2. 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.)

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  4. 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

  5. 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

  6. 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.

  7. 降脂抗凝联合作用对兔激素性股骨头坏死骨细胞凋亡的影响%Impact of Lipid Lowering and Anti-coagulant Combined Application on the Femoral Bone Cell Apoptosis in Rabbit with Steroid-induced Osteonecrosis

    Institute of Scientific and Technical Information of China (English)

    李挺松; 肖增明; 黄秋嫔; 劳山; 杨劲松; 罗高斌

    2014-01-01

    Objective To investigate the combined effects of lipid lowering and anti-coagulant on the femoral bone cell apoptosis in rabbit with ste-roid-induced osteonecrosis. Methods A total of 44 female Japanese white rabbits were randomly divided into three groups:normal saline group (CTR group,12 rabbits),steroid-induced osteonecrois of femoral group(SIONF group,16 rabbits),and atorvastatin warfarin treated group(AW group,16 rabbits). Intravenous injection of endotoxin of E.coli(10μg·kg-1)and intramuscular injection of methylprednisolone(20 mg·kg-1)were used to establish the SIONF rabbit model in SIONF group and AW group. CTR group was only administrated with saline. AW group was given atorv-astatin 2.5 mg·kg-1·d-1 and warfarin 1.0 mg·kg-1·d-1 by oral. Random sampling of two animals before the experiment two,four,six weeks after the experiment,and at the end of experiment(the 8th week),the venous blood was collected for testing serum total cholesterol(Tch),low density lipo-protein(LDL),prothrombin time(PT),tissue-type plasminogen activation time(t-PA),and taken bilateral hip X-rays. Then,all animals were scarified,and the femoral head bone cell apoptosis was determined. Results From the sixth week to the end of the experiment,Tch and LDL were slightly increased in CTR group and AW group,but no significant difference was found between the two groups. Tch and LDL were significantly in-creased in SIONF group than CTR group and AW group(P0.05),而SIONF组Tch、LDL显著高于CTR组及AW组(P<0.05);从实验第4周开始,AW组PT及t-PA较CTR组和SIONF组显著延长(P<0.05),SIONF组与CTR组比较PT、t-PA缩短(P<0.05);实验终点CTR组股骨头X线摄片正常,而SIONF组股骨头表面粗糙,软骨面塌陷,发生率为44%,AW组股骨头有类似SIONF组改变,但显著减轻,发生率为25%。实验第4周开始AW组骨细胞凋亡发生率(AI)开始升高持续到实验终点高达39,较CTR组AI(23)增高(P<0.05

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

    Institute of Scientific and Technical Information of China (English)

    孟繁宇; 施慧

    2015-01-01

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

  9. Effects of statins on serum lipids in patients with coronary heart disease risk factors and impact analysis%辛伐他汀对冠心病患者血脂水平影响及相关因素分析

    Institute of Scientific and Technical Information of China (English)

    周明; 田满荣

    2014-01-01

    Objective To investigate the effects of statins on coronary artery disease in patients with coro-nary heart disease and lipid regulating effect on curative effect .Methods 126 cases of patients with coronary heart disease were randomly divided into the control group of 60 cases and 66 cases in the treatment group ,the control group was given routine treatment of coronary heart disease ,the treatment group was treated with routine treatment with simv-astatin bedtime,before treatment and after 3,12 months when the determination of lipids ,liver function and renal func-tion index,and compared between the two groups of cardiovascular events .Results 3 months after treatment , TG, TC,LDL-C of the treatment group decreased significantly ,while the control group in 3,12 months after treatment,TC, TG,LDL-C had the rise of certain level(t=5.43,5.21,4.85,all P<0.05).The two groups after treatment in 3, 12 months in TC,TG,LDL-C had significant differences(t=5.32,5.78,5.64,6.15,6.41,6.06,all P<0.05).Dur-ing follow-up,patients in the treatment group 33 cases of cardiovascular events ,the control group of 81 cases,two groups of cardiovascular event rate had a significant difference (χ2 =13.42,P<0.01).Conclusion Statins can re-duce blood lipids in patients with coronary artery disease ,thereby reducing the patients appear related to cardiovascu-lar accidents,improve the treatment effect of coronary heart disease .%目的:探讨辛伐他汀对冠心病患者调脂效果以及对冠心病疗效的影响。方法126例冠心病患者按随机数字表法分为对照组60例及治疗组66例,对照组给予冠心病常规治疗,治疗组在常规治疗的基础上加用辛伐他汀睡前服用,在治疗前及治疗后3、12个月时测定血脂、肝功能及肾功能指标,并比较两组心血管事件的发生情况。结果治疗后3个月,治疗组TC、TG、LDL-C均显著降低( t=5.43、5.21、4.85,均P<0.05)。而对照组在治疗后3、12个月

  10. 树突状细胞与调节性T细胞在大鼠动脉粥样硬化中的作用及氟伐他汀的干预效应研究%The effects of fluvastatin on dendritic cells and regulatory T cells in experimental atherosclerosis rat model

    Institute of Scientific and Technical Information of China (English)

    牛川; 王清

    2015-01-01

    Objective To establish experimental atherosclerosis (AS) rat model ,and to investigate the effects of fluvastatin on dendritic cells(DCs) and regulatory T cells in the model .Methods Thirty male Wistar rats were divided into 3 groups:control group(fed with normal diet) ,high‐fat diet group(fed with AS feed) ,fluvastatin group(fed AS diet plus fluvastatin 0 .1 g · kg -1 · d-1 ) .For all the 3 groups ,the samples of aorta were obtained after 20 weeks .The flow cytometry was used to detect the immune‐phenotypic expression of DCs (CD11c ,HLA‐DR) and CD4+ CD25+ FoxP3+ regulatory T cells .Results (1)The numbers of CD11c+ and CD11c+ HLA‐DR+ double positive cells were significantly increased in the high‐fat and fluvastatin group compared with the control group(P<0 .01) ,while fluvastatin treatment reduced the CD11c+ and CD11c+ HLA‐DR+ expression of DCs sig‐nificantly(P<0 .01) .(2)the numbers of CD4+ CD25+ and CD4+CD25+ FoxP3+ regulatory T cells were higher significantly in fluv‐astatin group than the high‐fat group(P<0 .01) .No CD4+ CD25+ and CD4+CD25+ FoxP3+ regulatory T cells was detected in con‐trol group .(3)Correlation analysis between CD11c+ HLA‐DR+DCs and CD4+CD25+ FoxP3+ Treg showed that ,there was a nega‐tive correlation in high‐fat diet group and fluvastain group .Conclusion Fluvastatin could regulate immune‐phenotypic expression of DCs(CD11c ,HLA‐DR) and numbers of CD4+CD25+ FoxP3+ regulatory T cells ,which shows a new immune regulating mechanism of statins for its anti‐atherosclerotic effect .%目的:探讨树突状细胞(DCs)与调节性T细胞(Treg)在动脉粥样硬化过程中的作用机制及DCs与 Treg之间的相关性,观察氟伐他汀对大鼠主动脉粥样硬化的干预效应。方法30只雄性Wistar大鼠,分为3组。其中,对照组10只,喂养普通饲料;高脂组10只,喂养普通AS饲料;氟伐他汀组10只,喂养AS饲料+氟伐他汀0.1 g · kg -1· d-1。喂养20周,