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Sample records for astatine radiopharmaceuticals part

  1. 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.

  2. 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)

  3. DEVELOPMENT OF A RADIOPHARMACEUTICAL (PART II): FORMULATION, MARKING AND BIOLOGICAL DISTRIBUTION OF EC

    OpenAIRE

    López G., José; Universidad Nacional Mayor de San Marcos. Facultad de Química e Ingeniería Química Ciudad Universitaria, Av. Venezuela s/n, Lima 1 - Perú.; Robles Ñ., Ana; Instituto Peruano de Energía Nuclear - IPEN. Planta de Producción de Radioisótopos Central Nuclear RACSO - Huarangal, Lima 22 - Perú.; Reátegui S., Scila; Universidad Nacional Mayor de San Marcos. Facultad de Química e Ingeniería Química Ciudad Universitaria, Av. Venezuela s/n, Lima 1 - Perú.

    2014-01-01

    In Radiopharmacy the use of complexes as radiopharmaceutical requires that the procedure of labelling (complexing) achieves a radiochemical purity ot the complex ligand-Tc 99m greater than 98%. A study to find the chemical and physical parameters which allows the complexing of the EC ligand with Te 99m and the biological distribution is presented. En radiofarmacia, el uso de un complejo como radiofármaco requiere que el procedimiento de marcación (complejamiento) logre una pureza radioquím...

  4. 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

  5. Organometallic Radiopharmaceuticals

    Science.gov (United States)

    Alberto, Roger

    Although molecular imaging agents have to be synthesized ultimately from aqueous solutions, organometallic complexes are becoming more and more important as flexible yet kinetically stable building blocks for radiopharmaceutical drug discovery. The diversity of ligands, targets, and targeting molecules related to these complexes is an essential base for finding novel, noninvasive imaging agents to diagnose and eventually treat widespread diseases such as cancer. This review article covers the most important findings toward these objectives accomplished during the past 3-4 years. The two major available organometallic building blocks will be discussed in the beginning together with constraints for market introduction as imposed by science and industry. Since targeting radiopharmaceuticals are a major focus of current research in molecular imaging, attempts toward so-called technetium essential radiopharmaceuticals will be briefly touched in the beginning followed by the main discussion about the labeling of targeting molecules such as folic acid, nucleosides, vitamins, carbohydrates, and fatty acids. At the end, some new strategies for drug discovery will be introduced together with results from organometallic chemistry in water. The majority of the new results have been achieved with the [99mTc(OH2)3(CO)3]+ complex which will, though not exclusively, be a focus of this review.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Eleventh international symposium on radiopharmaceutical chemistry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    This document contains abstracts of papers which were presented at the Eleventh International Symposium on Radiopharmaceutical Chemistry. Sessions included: radiopharmaceuticals for the dopaminergic system, strategies for the production and use of labelled reactive small molecules, radiopharmaceuticals for measuring metabolism, radiopharmaceuticals for the serotonin and sigma receptor systems, labelled probes for molecular biology applications, radiopharmaceuticals for receptor systems, radiopharmaceuticals utilizing coordination chemistry, radiolabelled antibodies, radiolabelling methods for small molecules, analytical techniques in radiopharmaceutical chemistry, and analytical techniques in radiopharmaceutical chemistry.

  15. 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.

  16. 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.

  17. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  18. The development of cyclotron radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Seung Dae; Chun, K. W.; Suh, Y. S.; Lee, J. D.; Ahn, S. H. and others

    1999-03-01

    The purpose of this project is to developthe radiopharmaceuticals and automatic synthetic unit for labelled compounds, and to establish mass production system of radiopharmaceuticals. These will contribute to the early diagnosis of the disease hard to cure. The contents of this project are as follows, the development of the radiopharmaceutical for imaging of cancer, the development of automatic synthesizer for the synthesis of radio-pharmaceuticals, the development of hormone derivatives labelled with {sup 12}'3I, the development of the radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for imaging of myocardial metabolism.

  19. Radiopharmaceuticals for diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, D.E.

    1990-06-01

    During this grant period 1 January 1988--31 December 1990, we have successfully developed a number of new approaches to fluorine-18 labeled compounds, prepared several new radiotracers for both animal studies and eventual clinical trials, and explored the utility of a high-quality industrial robot in radiopharmaceutical applications. The progress during the last grant period is summarized briefly in the following sections. Publications arising from this research are listed below and can be found in Appendix I. 1 fig.

  20. Cyclotrons and positron emitting radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, A.P.; Fowler, J.S.

    1984-01-01

    The state of the art of Positron Emission Tomography (PET) technology as related to cyclotron use and radiopharmaceutical production is reviewed. The paper discusses available small cyclotrons, the positron emitters which can be produced and the yields possible, target design, and radiopharmaceutical development and application. 97 refs., 12 tabs. (ACR)

  1. Radiopharmaceuticals in Acute Porphyria.

    Science.gov (United States)

    Schreuder, Nanno; Mamedova, Ilahä; Jansman, Frank G A

    2016-10-01

    The acute porphyrias are a group of rare metabolic disorders of the heme biosynthetic pathway. Carriers of the acute porphyria gene are prone to potentially fatal acute attacks, which can be precipitated by drug exposure. It is therefore important to know whether a drug is safe for carriers of the acute porphyria gene. In this study, radiopharmaceuticals were assessed on their porphyrogenicity (ie, the potential of a drug to induce an attack). The assessment was conducted by classifying the drugs according to the Thunell model. From 41 radiopharmaceuticals assessed, I-131 norcholesterol, Tc-99m mebrofenin, Tc-99m phytate, Tc-99m sestamibi, and Tl-201 chloride were classified as possibly porphyrogenic. I-131 norcholesterol, Tc-99m mebrofenin, Tc-99m phytate, Tc-99m sestamibi, and Tl-201 chloride should not be prescribed for patients experiencing acute porphyria unless an urgent indication is present and no safer alternative is available. In such cases, potential users should seek advice from a porphyria expert. Preventive measures may also be required. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  2. 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...

  3. 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

  4. Development of radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyung Bae; Kim, J. R.; Shin, B. C.; Kim, Y. M.; Cho, U. K.; Han, K. H.; Chung, Y. J.; Shin, H. Y.; Hong, S. B.

    1997-09-01

    To overcome many problems caused by external radiation therapy, we have developed a new agent for internal radiation therapy, which is administered directly to the lesions and irradiate {beta}-rays resulting in maximized therapeutic effect and minimized radiation damage to normal tissues or organs to nearby. In the same reasons, we have also developed a new radioactive patch for the treatment of skin cancer using {beta}-emitting radionuclide. We prepared for {sup 166}Ho-chitosan complex ({sup 166}Ho-CHICO) which is potential radiopharmaceuticals for the treatment of liver cancer, peritoneal cancer metastasized from stomach cancer, ovarian cancer, and rheumatoid arthritis in knee joints. We carried out various experiments such as evaluation of absorbed dosimetry, studies on absorption, distribution, metabolism, and excretion (ADME) and clinical trials with {sup 166}Ho-CHICO. For commercialization of {sup 166}Ho-CHICO, we evaluated its toxicity, efficacy and safety, and then prepared documents for submission to the Mininstry of Health and Welfare to get license as an investigational new drug. {sup 166}Ho-Patch for skin cancer treatment was prepared by neutron irradiation of pre-made non-radioactive {sup 165}Ho-Patch. We evaluated the efficacy and safety of {sup 166}Ho-Patch in the treatment of skin cancer using an animal model and in clinical cases. (author). 49 refs., 15 tabs., 36 figs.

  5. 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...

  6. Bone-seeking therapeutic radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Srivastava Suresh C.

    2002-01-01

    Full Text Available Bone-seeking therapeutic radiopharmaceuticals are utilized on the basis of the radionuclide?s particulate emissions (primarily low to intermediate beta emission. The requirements therefore are different from those of bone imaging agents that consist mainly of short-lived single photon emitters. Lately, the therapeutic bone seeking radiopharmaceuticals have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients, for the treatment of joint pain resulting from inflamed synovium (radiosynoviorthesis, or radiosynovectomy, or from various other forms of arthritic disease. There is, however, a paucity of published data on the bio-pharmacokinetics of these agents when used following intravenous administration for bone pain palliation. This paper will briefly review and summarize the presently available chemical and biopharmacokinetic information on the various clinically approved as well as experimental bone-localizing therapeutic radiopharmaceuticals, and make projections on their clinical application for the treatment of primary/metastatic cancer in bone.

  7. Preparation of radiopharmaceuticals labeled with metal radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1992-06-01

    We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides.

  8. Radiopharmaceuticals for diagnosis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    In the period 1969-1986, this project was directed to the evolution of target-specific labeled chemicals useful for nuclear medical imaging, especially radioactive indicators suited to tracing adrenal functions and localizing tumors in the neuroendocrine system. Since 1986, this project research has focused on the chemistry of positron emission tomography (PET) ligands. This project has involved the evaluation of methods for radiochemical syntheses with fluorine-18, as well as the development and preliminary evaluation of new radiopharmaceuticals for positron emission tomography. In the radiochemistry area, the ability to predict fluorine-18 labeling yields for aromatic substitution reactions through the use of carbon-13 NMR analysis was studied. Radiochemical yields can be predicted for some structurally analogous aromatic compounds, but this correlation could not be generally applied to aromatic substrates for this reaction, particularly with changes in ring substituents or leaving groups. Importantly, certain aryl ring substituents, particularly methyl groups, appeared to have a negative effect on fluorination reactions. These observations are important in the future design of syntheses of complicated organic radiopharmaceuticals. In the radiopharmaceutical area, this project has supported the development of a new class of radiopharmaceuticals based on the monoamine vesicular uptake systems. The new radioligands, based on the tetrabenazine structure, offer a new approach to the quantification of monoaminergic neurons in the brain. Preliminary primate imaging studies support further development of these radioligands for PET studies in humans. If successful, such radiopharmaceuticals will find application in studies of the causes and treatment of neurodegenerative disorders such as Parkinson`s disease.

  9. 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....

  10. Radiation dose estimates for radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E. [Oak Ridge Inst. of Science and Education, TN (United States). Radiation Internal Dose Information Center

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  11. Radiopharmaceuticals drug interactions: a critical review

    Energy Technology Data Exchange (ETDEWEB)

    Santos-Oliveira, Ralph [Comissao Nacional de Energia Nuclear (CNEN/CRCN-NE), Recife, PE (Brazil). Centro Regional de Ciencias Nucleares. Servico de Controle de Qualidade]. E-mail: roliveira@cnen.gov.br; Smith, Sheila W. [University of Maryland, Baltimore, MF (United States). School of Pharmacy and Medicine. Dept. of Pharmaceutical Health Service Research; Carneiro-Leao, Ana Maria A. [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil). Dept. de Morfologia e Fisiologia Animal

    2008-12-15

    Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance) or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here, we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions. (author)

  12. 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.

  13. 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.

  14. Calibration and qualification of equipment in the pharmaceutical industry: emphasis on radiopharmaceuticals production

    Energy Technology Data Exchange (ETDEWEB)

    Melero, Laura T.U.H.; Silva, Katia S. da S.; Zanette, Camila; Araujo, Elaine B. de; Mengatti, Jair [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The calibration and qualification of equipment are listed items in RDC number 17 of 2010 which refers about the Good Manufacturing Practice (GMP) of medicaments and RDC number 63 of 2009 which refers about GMP of Radiopharmaceuticals. Both are essential requirements since they are involved in process control to attend the regulatory criteria and are a key part of the validation process. The aim of this work is presenting the importance of calibration and qualification, and the routine use of equipment and facilities in industrial scale production of radiopharmaceuticals in the IPEN/CNEN. The radiopharmacy of IPEN is a pharmaceutical industry that produces radiopharmaceuticals for diagnosis and therapy. It was the pioneer institute in production of radioisotopes and radiopharmaceuticals in Brazil. Currently, 38 products are distributed to the nuclear medicine centers, including primary radioisotopes, labeled molecules and lyophilized reagents for labeling with technetium-99m. To fulfill the GMP requirements for quality assurance of products, several factors must be considered including infrastructure, equipment and raw materials beyond, obviously, the whole production process should be controlled until the release of the final product. Therefore, the calibration and verification of equipment, instruments and other appliances used in the production and quality control should be performed. A program of calibration, qualification and requalification of equipment used in production and quality control of radiopharmaceuticals is necessary for the validation of production processes and analytical methods, and should be established for quality assurance of produced radiopharmaceuticals. (author)

  15. Improving radiopharmaceutical supply chain safety by implementing bar code technology.

    Science.gov (United States)

    Matanza, David; Hallouard, François; Rioufol, Catherine; Fessi, Hatem; Fraysse, Marc

    2014-11-01

    The aim of this study was to describe and evaluate an approach for improving radiopharmaceutical supply chain safety by implementing bar code technology. We first evaluated the current situation of our radiopharmaceutical supply chain and, by means of the ALARM protocol, analysed two dispensing errors that occurred in our department. Thereafter, we implemented a bar code system to secure selected key stages of the radiopharmaceutical supply chain. Finally, we evaluated the cost of this implementation, from overtime, to overheads, to additional radiation exposure to workers. An analysis of the events that occurred revealed a lack of identification of prepared or dispensed drugs. Moreover, the evaluation of the current radiopharmaceutical supply chain showed that the dispensation and injection steps needed to be further secured. The bar code system was used to reinforce product identification at three selected key stages: at usable stock entry; at preparation-dispensation; and during administration, allowing to check conformity between the labelling of the delivered product (identity and activity) and the prescription. The extra time needed for all these steps had no impact on the number and successful conduct of examinations. The investment cost was reduced (2600 euros for new material and 30 euros a year for additional supplies) because of pre-existing computing equipment. With regard to the radiation exposure to workers there was an insignificant overexposure for hands with this new organization because of the labelling and scanning processes of radiolabelled preparation vials. Implementation of bar code technology is now an essential part of a global securing approach towards optimum patient management.

  16. Radiopharmaceuticals in PET, Progress and Promise

    Science.gov (United States)

    Wolf, A. P.; Fowler, J. S.

    1988-11-01

    It is the intention of this presentation to focus on the current state of radiopharmaceuticals for PET and where this is leading us. PET radiopharmaceuticals can be broken down into perhaps seven categories at present with each being applicable to a different aspect of human biochemistry. These are: metabolic probes, neurochemical probes, enzyme probes, ion channel blockers, blood flow agents, ethical drugs and other positron emitters.

  17. Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective.

    Science.gov (United States)

    Aerts, Joel; Ballinger, James R; Behe, Martin; Decristoforo, Clemens; Elsinga, Philip H; Faivre-Chauvet, Alain; Mindt, Thomas L; Kolenc Peitl, Petra; Todde, Sergio C; Koziorowski, Jacek

    2014-08-01

    This document is meant to complement Part B of the EANM 'Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals' issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution. Copyright © 2014 John Wiley & Sons, Ltd.

  18. (Coordinated research of chemotherapeutic agents and radiopharmaceuticals)

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, P.C.

    1991-01-14

    The traveler received a United Nations Development Program (UNDP) Award for Distinguished Scientists to visit Indian Research Institutions including Central Drug Research Institute (CDRI), Lucknow, the host institution, in cooperation with the Council of Scientific and Industrial Research (CSIR) of India. At CDRI, the traveler had meetings to discuss progress and future directions of on-going collaborative research work on nucleosides and had the opportunity to initiate new projects with the divisions of pharmacology, biopolymers, and membrane biology. As a part of this program, the traveler also visited Sanjay Gandhi Post Graduate Institute (SGPI) of Medical Sciences, Lucknow; Board of Radiation and Isotope Technology (BRIT) and Bhabha Atomic Research Center (BARC), Bombay; Variable Energy Cyclotron Center (VECC) and Indian Institute of Chemical Biology, Calcutta. He also attended the Indo-American Society of Nuclear Medicine Meeting held in Calcutta. The traveler delivered five seminars describing various aspects of radiopharmaceutical development at the Oak Ridge National Laboratory (ORNL) and discussed the opportunities for exchange visits to ORNL by Indian scientists.

  19. Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals

    OpenAIRE

    Todde, Sergio; Stopar, Tanja; Mikolajczak, Renata; Farstad, Brit; Elsinga, Philip; Westera, Gerrit; Faivre-Chauvet, Alan; Meyer, Geerd; Penuelas, Ivan; Decristoforo, Clemens

    2010-01-01

    This guidance is meant as a guidance to Part B of the EANM ?Guidelines on Good Radiopharmacy Practice (GRPP)? issued by the Radiopharmacy Committee of the EANM (see www.eanm.org), covering the small-scale ?in house? preparation of radiopharmaceuticals which are not kit procedures. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of, for example, PET, therapeutic or other radiopharmaceuticals which are not intended for ...

  20. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  1. 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).

  2. The current situation and future prospects of radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Atsushi [Okayama Univ. (Japan). School of Medicine

    2001-11-19

    Radiopharmaceuticals play an important role in nuclear medicine. In this paper, nuclear medicine relating to radiopharmaceuticals was briefly described. And I would like to focus on the current situation and future prospects of radiopharmaceuticals. Nuclear medicine in this century should take the following directions. Firstly, cancer treatment by radionuclides will be one of the promising fields in oncology. Secondly, in order to achieve evidence-based medicine, sensitive, quantitative imaging using the nuclides will be necessary in nuclear medicine. Under these circumstances, it is important to develop radiopharmaceuticals for sensitive, quantitative imaging and therapeutic radiopharmaceuticals. (author)

  3. Computational system for activity calculation of radiopharmaceuticals

    African Journals Online (AJOL)

    ... this is specially practised in big countries like Brazil where the distance from one state to other is bigger than one country compared to others in continents like Europe. The purpose of this paper is to describe a computational system developed to evaluate the dose of radiopharmaceuticals during the production until the ...

  4. Radiopharmaceuticals for imaging chronic lymphocytic inflammation

    NARCIS (Netherlands)

    Malviya, Gaurav; De Vries, Erik F. J.; Dierckx, Rudi A.; Signore, Alberto

    In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the

  5. Computational system for activity calculation of radiopharmaceuticals

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... The preparation of radiopharmaceuticals for distribution to several hospitals is practised widely and the transport is usually by road and plain, this is specially practised in big countries like Brazil where the distance from one state to other is bigger than one country compared to others in continents like.

  6. Quality control of positron emission tomography radiopharmaceuticals: An institutional experience.

    Science.gov (United States)

    Shukla, Jaya; Vatsa, Rakhee; Garg, Nitasha; Bhusari, Priya; Watts, Ankit; Mittal, Bhagwant R

    2013-10-01

    To study quality control parameters of routinely prepared positron emission tomography (PET) radiopharmaceuticals. Three PET radiopharmaceuticals fluorine-18 fluorodeoxyglucose (F-18 FDG), N-13 ammonia (N-13 NH3), and Ga-68 DOTATATE (n = 25 each), prepared by standardized protocols were used. The radionuclide purity, radiochemical purity, residual solvents, pH, endotoxins, and sterility of these radiopharmaceuticals were determined. The physical half-life of radionuclide in radiopharmaceuticals, determined by both graphical and formula method, demonstrated purity of radionuclides used. pH of all PET radiopharmaceuticals used was in the range of 5-6.5. No microbial growth was observed in radiopharmaceutical preparations. The residual solvents, chemical impurity, and pyrogens were within the permissible limits. All three PET radiopharmaceuticals were safe for intravenous administration.

  7. Simplification of Methods for PET Radiopharmaceutical Syntheses

    Energy Technology Data Exchange (ETDEWEB)

    Kilbourn, Michael, R.

    2011-12-27

    In an attempt to develop simplified methods for radiochemical synthesis of radiopharmaceuticals useful in Positron Emission Tomography (PET), current commercially available automated synthesis apparati were evaluated for use with solid phase synthesis, thin-film techniques, microwave-accelerated chemistry, and click chemistry approaches. Using combinations of these techniques, it was shown that these automated synthesis systems can be simply and effectively used to support the synthesis of a wide variety of carbon-11 and fluorine-18 labeled compounds, representing all of the major types of compounds synthesized and using all of the common radiochemical precursors available. These techniques are available for use to deliver clinically useful amounts of PET radiopharmaceuticals with chemical and radiochemical purities and high specific activities, suitable for human administration.

  8. Transport processes of radiopharmaceuticals and -modulators

    Directory of Open Access Journals (Sweden)

    Langguth Peter

    2011-06-01

    Full Text Available Abstract Radiotherapy and radiology have been indispensable components in cancer care for many years. The detection limit of small tumor foci as well as the development of radio-resistance and severe side effects towards normal tissues led to the development of strategies to improve radio-diagnostic and -therapeutic approaches by pharmaceuticals. The term "radiopharmaceutical" has been used for drugs labeled with radioactive tracers for therapy or diagnosis. In addition, drugs have been described to sensitize tumor cells to radiotherapy (radiosensitizers or to protect normal tissues from detrimental effects of radiation (radioprotectors. The present review summarizes recent concepts on the transport of radiopharmaceuticals, radiosensitizers, and radioprotectors in cells and tissues, e.g. by ATP-binding cassette transporters such as P-glycoprotein. Strengths and weaknesses of current strategies to improve transport-based processes are discussed.

  9. Development of 89Zr Labelled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    WANG Li-zhen;YANG Min

    2016-10-01

    Full Text Available Positron emission tomography (PET is the most advanced molecular imaging technology with the advantage of high sensitivity and quantity analysis. Molecule probe is the key factor for PET. 89Zr is a novel imaging nuclide and suitable for labeling macromolecular bioactive substances such as antibody due to its favorably long half-life and energy. This review outlined the recent development of the production of 89Zr, labeling methods and application of 89Zr labelled radiopharmaceuticals.

  10. Radiopharmaceuticals drug interactions: a critical review

    Directory of Open Access Journals (Sweden)

    Ralph Santos-Oliveira

    2008-12-01

    Full Text Available Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here,we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions.Os radiofármacos desempenham função crítica na medicina moderna, primariamente para fins diagnósticos, mas também no monitoramento da progressão de doenças assim como na avaliação de respostas ao tratamento. O uso da tecnologia por imagem tem crescido e conseqüentemente as prescrições de medicamentos (radiofármacos em especial com esse propósito. Este fato, aumenta o risco de interações entre medicamentos e radiofármacos. Interações que podem ter um impacto na

  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. 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.

  13. Preparation of Radiopharmaceuticals Labeled with Metal Radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    2012-02-16

    The overall goal of this project was to develop methods for the production of metal-based radionuclides, to develop metal-based radiopharmaceuticals and in a limited number of cases, to translate these agents to the clinical situation. Initial work concentrated on the application of the radionuclides of Cu, Cu-60, Cu-61 and Cu-64, as well as application of Ga-68 radiopharmaceuticals. Initially Cu-64 was produced at the Missouri University Research Reactor and experiments carried out at Washington University. A limited number of studies were carried out utilizing Cu-62, a generator produced radionuclide produced by Mallinckrodt Inc. (now Covidien). In these studies, copper-62-labeled pyruvaldehyde Bis(N{sup 4}-methylthiosemicarbazonato)-copper(II) was studied as an agent for cerebral myocardial perfusion. A remote system for the production of this radiopharmaceutical was developed and a limited number of patient studies carried out with this agent. Various other copper radiopharmaceuticals were investigated, these included copper labeled blood imaging agents as well as Cu-64 labeled antibodies. Cu-64 labeled antibodies targeting colon cancer were translated to the human situation. Cu-64 was also used to label peptides (Cu-64 octriatide) and this is one of the first applications of a peptide radiolabeled with a positron emitting metal radionuclide. Investigations were then pursued on the preparation of the copper radionuclides on a small biomedical cyclotron. A system for the production of high specific activity Cu-64 was developed and initially the Cu-64 was utilized to study the hypoxic imaging agent Cu-64 ATSM. Utilizing the same target system, other positron emitting metal radionuclides were produced, these were Y-86 and Ga-66. Radiopharmaceuticals were labeled utilizing both of these radionuclides. Many studies were carried out in animal models on the uptake of Cu-ATSM in hypoxic tissue. The hypothesis is that Cu-ATSM retention in vivo is dependent upon the

  14. Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Russell, J.R. [Univ. of Maryland, Baltimore, MD (United States); Stabin, M.G.; Sparks, R.B. [Oak Ridge Inst. for Science and Education, TN (United States)

    1999-01-01

    The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper, after identification of radiopharmaceuticals often administered to women of childbearing age, the most recent data available on the placental crossover of these radiopharmaceuticals was used (with standard kinetic models describing the maternal distribution and retention and with the best available physical models) to obtain fetal dose estimates for these radiopharmaceuticals were identified as those most commonly administered to women of childbearing years. The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. Radiation dose estimates are presented in early pregnancy and at 3-, 6-, and 9-months gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose). 46 refs., 1 fig., 5 tabs.

  15. Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals.

    Science.gov (United States)

    Elsinga, Philip; Todde, Sergio; Penuelas, Ivan; Meyer, Geerd; Farstad, Brit; Faivre-Chauvet, Alain; Mikolajczak, Renata; Westera, Gerrit; Gmeiner-Stopar, Tanja; Decristoforo, Clemens

    2010-05-01

    This guidance is meant as a guidance to Part B of the EANM "Guidelines on Good Radiopharmacy Practice (GRPP)" issued by the Radiopharmacy Committee of the EANM (see www.eanm.org ), covering the small-scale "in house" preparation of radiopharmaceuticals which are not kit procedures. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of, for example, PET, therapeutic or other radiopharmaceuticals which are not intended for commercial purposes or distribution.

  16. Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules : a European perspective

    NARCIS (Netherlands)

    Aerts, Joel; Ballinger, James R.; Behe, Martin; Decristoforo, Clemens; Elsinga, Philip H.; Faivre-Chauvet, Alain; Mindt, Thomas L.; Peitl, Petra Kolenc; Todde, Sergio C.; Koziorowski, Jacek

    This document is meant to complement Part B of the EANM Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals' issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of

  17. Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals

    NARCIS (Netherlands)

    Elsinga, Philip; Todde, Sergio; Penuelas, Ivan; Meyer, Geerd; Farstad, Brit; Faivre-Chauvet, Alain; Mikolajczak, Renata; Westera, Gerrit; Gmeiner-Stopar, Tanja; Decristoforo, Clemens

    This guidance is meant as a guidance to Part B of the EANM "Guidelines on Good Radiopharmacy Practice (GRPP)" issued by the Radiopharmacy Committee of the EANM (see www.eanm.org), covering the small-scale "in house" preparation of radiopharmaceuticals which are not kit procedures. The aim is to

  18. Activity in the gastrointestinal tract after administration of bone-seeking radiopharmaceuticals. Experimental studies in mice

    Energy Technology Data Exchange (ETDEWEB)

    Cronhjort, M. [Karolinska Hospital, Stockholm (Sweden). Dept. of Diagnostic Radiology; Jonsson, C. [Karolinska Hospital, Stockholm (Sweden). Hospital Physics; Nilsson, S.O. [Karolinska Pharmacy, Stockholm (Sweden); Garmelius, B. [Karolinska Pharmacy, Stockholm (Sweden); Jacobsson, H. [Karolinska Hospital, Stockholm (Sweden). Dept. of Diagnostic Radiology

    1996-09-01

    Purpose: To test the possibility that (radio)activity of non-pertechnetate nature is excreted into the gastrointestinal tract at bone scintigraphy. Material and Methods: The distribution of a bone-seeking radiopharmaceutical ({sup 99m}Tc-HDP) was studied in an experimental mouse system by dissecting different organs and assessing their activity with a gamma-counter. Results: A comparison of the activity of the submandibular glands, which are assumed to accumulate only pertechnetate, and the gastrointestinal tract showed that a significant fraction of the activity excreted into the gastrointestinal tract did not consist of pertechnetate. Part of the excretion took place in the stomach. It was not connected to a specific bone-seeking agent or {sup 99}Mo/{sup 99m}Tc generator. Nor did it increase with time between make-up and injection. The excretion of the non-pertechnetate activity was reduced by cimetidine and omeprazole. These gastric-secretion blocking drugs did not reduce excretion of pertechnetate or significantly affect the general distribution of the radiopharmaceutical. Conclusion: There is a significant excretion of non-pertechnetate activity in the gastrointestinal tract. Part of this may be caused by excretion of the undegraded radiopharmaceutical by the stomach mucosa. (orig.).

  19. Use of radiopharmaceuticals in Finland in 1997

    Energy Technology Data Exchange (ETDEWEB)

    Korpela, H

    1999-04-01

    The use of radiopharmaceuticals in diagnostics and therapy has been surveyed by STUK - Radiation and Nuclear Safety Authority. In 1997 the number of nuclear medicine examinations was 51,700, and the number of treatments 2,240. In 1994 the number of nuclear medicine examinations had been 50,900, and the number of treatments 2,150. In 1997 the collective effective dose received by patients was 207 manSv, and the mean effective dose received by the population was 0.04 mSv per person. In 1994 the collective effective dose had been 220 manSv. Numbers of nuclear medicine examinations and treatments have not changed much from 1994. The collective effective dose has slightly decreased. The main reason for the reduction is decreased use of the radionuclide {sup 131}I. (orig.) 4 refs.

  20. The Radiochemical and Radiopharmaceutical Applications of Radium

    Directory of Open Access Journals (Sweden)

    Gott Matthew

    2016-01-01

    Full Text Available This review focuses on the chemistry and application of radium isotopes to environmental monitoring, analytical, and medicinal uses. In recent years, radium has been used primarily as a tracer to study the migration of radioactive substances in environmental systems. Tracing the naturally occurring radium isotopes in mineral and water sources allows for the determination of source location, residence time, and concentrations. An understanding of the concentration of radionuclides in our food and water sources is essential to everyone’s health as alpha particle decay is highly damaging in vivo. Due to this high radiobiological effectiveness, there is increased interest in using alpha-emitting radionuclides to prepare new, therapeutic radiopharmaceutical drugs. Selected studies from the recent literature are provided as examples of these modern applications of radium isotopes.

  1. Preparações radiofarmacêuticas e suas aplicações Radiopharmaceuticals and applications

    Directory of Open Access Journals (Sweden)

    Rita Oliveira

    2006-06-01

    Full Text Available Os radiofármacos são compostos, sem ação farmacológica, que têm na sua composição um radionuclídeo e são utilizados em Medicina Nuclear para diagnóstico e terapia de várias doenças. Para aplicações de diagnóstico em Medicina Nuclear utilizam-se radiofármacos que apresentam na sua constituição radionuclídeos emissores de radiação gama ou emissores de pósitrons (beta+, já que o decaimento destes radionuclídeos dá origem a radiação eletromagnética penetrante, que consegue atravessar os tecidos e pode ser detectada externamente. Os radiofármacos para terapia devem incluir na sua composição um radionuclídeo emissor de partículas ionizantes (a , b- ou elétrons Auger, pois a sua ação se baseia na destruição seletiva de tecidos. Existem dois métodos tomográficos para aquisição de imagens em Medicina Nuclear: o SPECT (Tomografia Computarizada de Emissão de Fóton Único, que utiliza radionuclídeos emissores gama (99mTc, 123I, 67Ga, 201Tl e o PET (Tomografia por Emissão de Pósitrons, que usa radionuclídeos emissores de pósitrons ( 11C, 13N, 15O, 18F. Os radiofármacos podem ser classificados em radiofármacos de perfusão (ou 1ª geração e radiofármacos específicos (ou 2ª geração. Os radiofármacos de perfusão são transportados no sangue e atingem o órgão alvo na proporção do fluxo sanguíneo. Os radiofármacos ditos específicos contêm molécula biologicamente ativa, que se liga a receptores celulares e que deve manter a sua bioespecificidade mesmo após ligação ao radionuclídeo. Assim, nestes radiofármacos, a fixação em tecidos ou órgãos é determinada pela capacidade da biomolécula de reconhecer receptores presentes nessas estruturas biológicas. As preparações radiofarmacêuticas são obtidas prontas para uso, em kits frios ou em preparações autólogas. De acordo com o tipo de preparação, existe um processo de controle de qualidade próprio. A maior parte dos radiof

  2. Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine - a review

    Energy Technology Data Exchange (ETDEWEB)

    Eberlein, Uta; Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Broeer, Joern Hendrik; Nosske, Dietmar [Federal Office for Radiation Protection, Department of Radiation Protection and Health, Oberschleissheim (Germany); Vandevoorde, Charlot; Bacher, Klaus [Ghent University, Department of Basic Medical Sciences, Division of Medical Physics, Ghent (Belgium); Santos, Paula; Bardies, Manuel [INSERM UMR892, Nantes (France)

    2011-12-15

    The impact on patients' health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET, we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed. In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained. (orig.)

  3. Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Pol, Jochem van der; Voeoe, Stefan [Maastricht University Medical Centre (MUMC+), Department of Radiology and Nuclear Medicine, Postbox 5800, Maastricht (Netherlands); Bucerius, Jan; Mottaghy, Felix M. [Maastricht University Medical Centre (MUMC+), Department of Radiology and Nuclear Medicine, Postbox 5800, Maastricht (Netherlands); University Hospital, RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany)

    2017-07-15

    Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents. A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords ''misadministration'', ''extravasation'', ''paravascular infiltration'', combined with ''tracer'', ''radionuclide'', ''radiopharmaceutical'', and a list of keywords referring to clinically used tracers (i.e. ''Technetium-99m'', ''Yttrium-90''). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised. Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature. Extravasation of diagnostic radiopharmaceuticals is common. {sup 99m}Tc, {sup 123}I, {sup 18}F, and {sup 68}Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation. (orig.)

  4. Pediatric patients: criteria for radiopharmaceuticals activities in diagnostic procedures

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Felipe Simas dos; Oliveira, Silvia M. Velasques de, E-mail: simas@ird.gov.b, E-mail: silvia@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2009-07-01

    Recent studies recommend new criteria to determine radiopharmaceuticals activities per diagnostic procedures for children and teenagers. In USA, the criteria are: minimum and maximum activity and activity per body weight. The minimum activity is necessary for assuring the quality image due to the minimum requested statistical counting. The reduction of maximum activities minimizes the probability of detriment of radiation. In the European Union (EU), the Pediatric Dosage Card (PDC) proposes combined parameters: category of radiopharmaceutical, patient body weight and minimum activity per procedure. The PDC classifies the radiopharmaceuticals according to their biodistribution in the most sensitive organs. In Brazil, an investigation evaluated radiopharmaceuticals activities administered to 2,411 pediatric patients in sixteen institutions. The Brazilian mean activities per body weight, minimum and maximum activities used per institutions were compared with similar parameters surveyed in thirteen American hospitals. It was also used the PDC model to calculate the minimum activities per radiopharmaceuticals using recorded Brazilian patients corporal masses. The wider differences between Brazilian and USA installations were noticed for minimum activities by as much as a factor of 2 and 8. For {sup 67}Ga Citrate, the ranges of activities per patient corporal mass were by as much as a factor of 2 and 9 than activities used in USA. The range of maximum activities presented fewer differences, varying between 0.5 and 2 times for the radiopharmaceuticals studied. The present work needs the collaboration of the professional staff for discussion of the results, to promote regional surveys and to optimize pediatric patient protocols (author)

  5. Application of lectins to tumor imaging radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Shuji; Jay, M.

    1986-11-01

    We investigated the in vitro binding of /sup 125/I-lectins to Ehrlich ascites tumor (EAT) cells and in vivo uptake of /sup 125/I-lectins in Ehrlich solid tumor (EST) bearing mice. In in vitro binding assays, phaseolus vulgaris agglutinin (PHA), pisum sativum agglutinin (PSA), and concanavalia agglutinin (Con A) showed a high affinity for EAT cells. The in vivo biodistribution of /sup 125/I-lectins showed /sup 125/I-PSA to be significantly taken up into EST tissues 24 h postinjection. After IV injection of /sup 125/I-PSA, uptake of the radioactivity into the tumor tissues reached a maximum at 6 h, and thereafter decreased. Rapid disappearance of the radioactivity from blood and its excretion into kidney soon after injection of /sup 125/I-PSA were observed. When compared with the biodistribution of /sup 67/Ga-citrate in EST bearing mice 24 h postinjection, tumor to liver (T/B), tumor to muscle (T/M), and tumor to blood (T/B) ratios were superior for /sup 125/I-PSA. At 6 h postinjection, the T/B-ratio of /sup 125/I-PSA was 2.5, and this value may be sufficient to enable discernable diagnostic images. Our results suggest that PSA might be a useful tumor imaging radiopharmaceutical.

  6. Drug interaction with radiopharmaceuticals: a review

    Energy Technology Data Exchange (ETDEWEB)

    Bernardo-Filho, Mario; Santos-Filho, Sebastiao David; Moura, Egberto Gaspar de; Maiworm, Adalgisa Ieda; Bernardo, Luciana Camargo; Brito, Lavinia de Carvalho [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Orlando, Margarida Maria de Camoes [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Hospital Universitario Pedro Ernesto. Setor de Medicina Nuclear; Penas, Maria Exposito [Universidade Federal do Rio de Janeiro, RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Setor de Medicina Nuclear; Cardoso, Valbert Nascimento [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Lab. de Radioisotopos

    2005-10-15

    Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99m T, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemo perfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.(author)

  7. Traceability in the pharmaceutical industry: application to radiopharmaceutical production

    Energy Technology Data Exchange (ETDEWEB)

    Zanette, Camila; Melero, Laura T.U.H.; Araujo, Elaine B. de; Mengatti, Jair; Silva, Katia S. de S., E-mail: czanette@usp.br [Instituto de Pesquisas Energeticas e Nucleares, (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The development of tools to promote the traceability of the drugs in the pharmaceutical industry during all the production chain is a necessary requisite. The traceability system is applied to enable the identification of the origin, destination and exact location of the drug. Traceability optimizes the process chain, reduces errors, is a requirement for quality process, promotes safety for the user and assists in pharmacovigilance. The health regulatory agency in Brazil (ANVISA) will implement a tracking system for medicaments with RDC no. 59 of 2009, to control distribution since the producer until the patients in order to prevent the traffic and adulteration of drugs. Thus, this study discusses the importance and impact of the new traceability system proposed by ANVISA in the production and distribution of radiopharmaceuticals from the Nuclear and Energy Research Institute (IPEN-CNEN). The radiopharmaceuticals have a difference track when compared with another drug classes. In this context, this RDC would increase the price of the medicines by up to 10%, since it provides deployment of a single stamp supplied by the Mint. Considering that radiopharmaceuticals are not sold to the final consumer (patients), but only for accredited medical clinics and nuclear medicine physicians, and the transport of radiopharmaceuticals is performed by specialized companies licensed by CNEN (National Nuclear Energy Commission), the use of the stamp to ensure authenticity and prevent falsification should not be appropriated and represents and additional cost for the radiopharmaceuticals. (author)

  8. 188Re(V) Nitrido Radiopharmaceuticals for Radionuclide Therapy.

    Science.gov (United States)

    Boschi, Alessandra; Martini, Petra; Uccelli, Licia

    2017-01-19

    The favorable nuclear properties of rhenium-188 for therapeutic application are described, together with new methods for the preparation of high yield and stable 188Re radiopharmaceuticals characterized by the presence of the nitride rhenium core in their final chemical structure. 188Re is readily available from an 188W/188Re generator system and a parallelism between the general synthetic procedures applied for the preparation of nitride technetium-99m and rhenium-188 theranostics radiopharmaceuticals is reported. Although some differences between the chemical characteristics of the two metallic nitrido fragments are highlighted, it is apparent that the same general procedures developed for the labelling of biologically active molecules with technetium-99m can be applied to rhenium-188 with minor modification. The availability of these chemical strategies, that allow the obtainment, in very high yield and in physiological condition, of 188Re radiopharmaceuticals, gives a new attractive prospective to employ this radionuclide for therapeutic applications.

  9. 188Re(V Nitrido Radiopharmaceuticals for Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Alessandra Boschi

    2017-01-01

    Full Text Available The favorable nuclear properties of rhenium-188 for therapeutic application are described, together with new methods for the preparation of high yield and stable 188Re radiopharmaceuticals characterized by the presence of the nitride rhenium core in their final chemical structure. 188Re is readily available from an 188W/188Re generator system and a parallelism between the general synthetic procedures applied for the preparation of nitride technetium-99m and rhenium-188 theranostics radiopharmaceuticals is reported. Although some differences between the chemical characteristics of the two metallic nitrido fragments are highlighted, it is apparent that the same general procedures developed for the labelling of biologically active molecules with technetium-99m can be applied to rhenium-188 with minor modification. The availability of these chemical strategies, that allow the obtainment, in very high yield and in physiological condition, of 188Re radiopharmaceuticals, gives a new attractive prospective to employ this radionuclide for therapeutic applications.

  10. Drug interaction with radiopharmaceuticals: a review

    Directory of Open Access Journals (Sweden)

    Mario Bernardo-Filho

    2005-10-01

    Full Text Available Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99mT, can also be modified. These factors include drugs (synthetic and natural and dietary conditions, as well as some medical procedures (invasive or non-invasive, such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.Imagens clínicas são valiosas em Ciências da Saúde e a análise e a interpretação correta das mesmas auxiliam os profissionais, como médico, fisioterapeuta, terapeuta ocupacional, na tomada de decisões e subseqüentes ações terapêuticas e/ou de reabilitação. Além das doenças outros fatores podem interferir e afetar a biodisponibilidade dos radiofármacos (radiobiocomplexos e a qualidade das imagens (SPECT e PET. Além disso, a marcação de alguns desses radiobiocomplexos com Tc-99m, como proteínas plasmáticas, leucócitos e hemácias, também pode ser modificada. Entre esses fatores, estão drogas (sintéticas e naturais e condições alimentares, assim como alguns procedimentos médicos (invasivos e não invasivos, como a radioterapia, processos cirúrgicos, pr

  11. Preparation of radiopharmaceuticals labeled with metal radionuclides. Progress report, July 1, 1988--June 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1992-06-01

    We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides.

  12. Synthesis of oncological [11C]radiopharmaceuticals for clinical PET.

    Science.gov (United States)

    Lodi, Filippo; Malizia, Claudio; Castellucci, Paolo; Cicoria, Gianfranco; Fanti, Stefano; Boschi, Stefano

    2012-05-01

    Positron emission tomography (PET) is a nuclear medicine modality which provides quantitative images of biological processes in vivo at the molecular level. Several PET radiopharmaceuticals labeled with short-lived isotopes such as (18)F and (11)C were developed in order to trace specific cellular and molecular pathways with the aim of enhancing clinical applications. Among these [(11)C]radiopharmaceuticals are N-[(11)C]methyl-choline ([(11)C]choline), l-(S-methyl-[(11)C])methionine ([(11)C]methionine) and 1-[(11)C]acetate ([(11)C]acetate), which have gained an important role in oncology where the application of 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) is suboptimal. Nevertheless, the production of these radiopharmaceuticals did not reach the same level of standardization as for [(18)F]FDG synthesis. This review describes the most recent developments in the synthesis of the above-mentioned [(11)C]radiopharmaceuticals aiming to increase the availability and hence the use of [(11)C]choline, [(11)C]methionine and [(11)C]acetate in clinical practice. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Calix[4]arene rhenium(V) complexes as potential radiopharmaceuticals

    NARCIS (Netherlands)

    Bommel, K.J.C.; Verboom, Willem; Hulst, A.J.R.L.; Kooijman, Huub; Spek, Anthony L.; Reinhoudt, David

    2000-01-01

    The calix[4]arene platform was used for the syntheses of novel rhenium(V) complexes, that may have potential applications as radiopharmaceuticals. The reaction of ReO(PPh3)2Cl3 with tetradentate N2O2-calix[4]arene ligand 8 in ethanol gave the novel mixed-ligand rhenium complex 9 with the structure

  14. Development and application of peptide-based radiopharmaceuticals.

    NARCIS (Netherlands)

    Dijkgraaf, I.; Boerman, O.C.; Oyen, W.J.G.; Corstens, F.H.M.; Gotthardt, M.

    2007-01-01

    During the past decade, radiolabeled receptor-binding peptides have emerged as an important class of radiopharmaceuticals for tumor diagnosis and therapy. The specific receptor binding property of the ligand can be exploited by labeling the ligand with a radionuclide and using the radiolabeled

  15. Harvard-MIT research program in short-lived radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.

    1991-01-01

    This report presents research on radiopharmaceuticals. The following topics are discussed: antibody labeling with positron-emitting radionuclides; antibody modification for radioimmune imaging; labeling antibodies; evaluation of technetium acetlyacetonates as potential cerebral blood flow agents; and studies in technetium chemistry. (CBS)

  16. Development and clinical application of peptide-based radiopharmaceuticals.

    NARCIS (Netherlands)

    Gotthardt, M.; Boerman, O.C.; Behr, T.M.; Behe, M.; Oyen, W.J.G.

    2004-01-01

    Peptide-based radiopharmaceuticals have been introduced into clinical work more than a decade ago. The first and most successful imaging agent to date is the somatostatin analog octreotide. It is used for somatostatin receptor scintigraphy and also receptor-mediated peptide-radiotherapy of

  17. Quality control of PET radiopharmaceuticals using HPLC with electrochemical detection.

    Science.gov (United States)

    Nakao, Ryuji; Furutuka, Kenji; Yamaguchi, Masatoshi; Suzuki, Kazutoshi

    2006-04-01

    The usefulness of high-performance liquid chromatography with electrochemical detection (HPLC/ECD) in the quality control of positron emission tomography (PET) radiopharmaceuticals was evaluated for a number of substances. Chromatographic separation was performed using a reversed phase column and acetonitrile or 20 mM sodium phosphate buffer as the mobile phase. The effluent from the column was introduced into an electrochemical detector equipped with a glassy carbon electrode versus Ag/AgCl electrode operated in the direct current mode. In 19 of 21 PET radiopharmaceuticals studied, the compounds and corresponding precursors used in the synthesis of the radiopharmaceuticals could be successfully detected by the HPLC/ECD method. For 17 compounds with electroactive functional groups, such as aliphatic amines, phenols and aromatic amines, the detection limits were ppb levels for a 20-mul injection volume; this was significantly better compared with ultraviolet (UV) detection. This method could be applied to the analysis of [11C]MP4A, useful PET radiopharmaceutical for measuring acetylcholinesterase activity in the brain with no available UV absorbance.

  18. 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

  19. Deficiencies of product labeling directions for the preparation of radiopharmaceuticals.

    Science.gov (United States)

    Hung, Joseph C; Ponto, James A; Gadient, Katie R; Frie, Julia A; Aksamit, Carolyn M; Enquist, Cassandra L; Carrels, Katie E

    2004-01-01

    To identify potential deficiencies in product labeling (package insert) instructions for the preparation of radiopharmaceuticals. Preparation instructions, which include both reconstitution and quality control (QC) directions, as stated in the package inserts were evaluated for all commercially available reconstituted radiopharmaceuticals. Reviews of the package inserts were initially performed by each author, and then all identified deficiencies were compiled and evaluated by all authors. The preparation scenario for each package insert evaluated was based on a centralized nuclear pharmacy operation assuming typical support personnel, standard operating equipment, and workload. The instructions as stated in each package insert for the preparation (including QC) were rated as inadequate if a satisfactory preparation could not be prepared by a nuclear pharmacist or physician when instructions were followed exactly. Identified deficiencies in package insert instructions for the preparation of radiopharmaceuticals fell into the following five categories: (1) absent or incomplete directions (especially with regard to QC procedures); (2) restrictive directions (e.g., specific requirement to use designated needles, chromatography solvents, counting devices), (3) inconsistent directions (e.g., different reconstituted volumes for the same final drug product, unworkable expiration times); (4) impractical directions (e.g., unrealistically low reconstituted activity limits, dangerously high number of radiolabeled particles); and (5) vague directions (e.g., use of the words "should," "may," "recommend"). Manufacturers' directions for the preparation of radiopharmaceuticals often contain deficiencies and should be viewed as standard guidance rather than as requirements. Just as physicians are permitted to use U.S. Food and Drug Administration (FDA)-approved drugs for off-label indications, nuclear pharmacists should be allowed to use alternative methods for preparing

  20. Infection imaging with radiopharmaceuticals in the 21st century

    Energy Technology Data Exchange (ETDEWEB)

    Das, Satya S.; Wareham, David W. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Medical Microbiology; Britton, Keith E. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Nuclear Medicine; Hall, Anne V. [Harefield Hospital, Middlesex (United Kingdom). Microbiology Dept.

    2002-09-01

    Infection continues to be a major cause of morbidity and mortality worldwide. Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections such as abscesses, osteomyelitis, septic arthritis, endocarditis, and infections of prosthetic devices. Established techniques such as radiolabelled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear Medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals, such as radiolabelled anti-infectives (e.g. 99 m Tc ciprofloxacin). In addition to aiding early diagnosis of infection, through serial imaging these agents might prove very useful in monitoring the response to and determining the optimum duration of anti-infective therapy. This article reviews the current approach to infection imaging with radiopharmaceuticals nd the future direction it might take. (author)

  1. Gastrin releasing peptide (GRP) receptor targeted radiopharmaceuticals: A concise update

    Energy Technology Data Exchange (ETDEWEB)

    Smith, C.J.; Volkert, W.A.; Hoffman, T.J. E-mail: HoffmanT@health.missouri.edu

    2003-11-01

    The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.

  2. Radiopharmaceuticals and other compounds labelled with short-lived radionuclides

    CERN Document Server

    Welch, Michael J

    2013-01-01

    Radiopharmaceuticals and Other Compounds Labelled with Short-Lived Radionuclides covers through both review and contributed articles the potential applications and developments in labeling with short-lived radionuclides whose use is restricted to institutions with accelerators. The book discusses the current and potential use of generator-produced radionuclides as well as other short-lived radionuclides, and the problems of quality control of such labeled compounds. The book is useful to nuclear medicine physicians.

  3. USE OF RADIOPHARMACEUTICALS IN DIAGNOSTIC NUCLEAR MEDICINE IN THE UNITED STATES: 1960–2010

    OpenAIRE

    Drozdovitch, Vladimir; Brill, Aaron B.; Callahan, Ronald J.; Clanton, Jeffrey A.; DePietro, Allegra; Goldsmith, Stanley J; Greenspan, Bennett S.; Gross, Milton D; Hays, Marguerite T.; Moore, Stephen C.; Ponto, James A.; Shreeve, Walton W.; Melo, Dunstana R.; Linet, Martha S.; Simon, Steven L

    2015-01-01

    To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, we assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnosti...

  4. New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents

    National Research Council Canada - National Science Library

    Alice Brink; John R Helliwell

    2017-01-01

    .... The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals...

  5. Radiopharmaceuticals to monitor the expression of transferred genes in gene transfer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, L. I. [University of Alberta, Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-10-01

    The development and application of radiopharmaceuticals has, in many instances, been based on the pharmacological properties of therapeutic agents. The molecular biology-biotechnology revolution has had an important impact on treatment of diseases, in part through the reduced toxicity of `biologicals`, in part because of their specificity for interaction at unique molecular sites and in part because of their selective delivery to the target site. Immunotherapeutic approaches include the use of monoclonal antibodies (MABs), MAB-fragments and chemotactic peptides. Such agents currently form the basis of both diagnostic and immunotherapeutic radiopharmaceuticals. More recently, gene transfer techniques have been advanced to the point that a new molecular approach, gene therapy, has become a reality. Gene therapy offers an opportunity to attack disease at its most fundamental level. The therapeutic mechanism is based on the expression of a specific gene or genes, the product of which will invoke immunological, receptor-based or enzyme-based therapeutic modalities. Several approaches to gene therapy of cancer have been envisioned, the most clinically-advanced concepts involving the introduction of genes that will encode for molecular targets nor normally found in healthy mammalian cells. A number of gene therapy clinical trials are based on the introduction of the Herpes simplex virus type-1 (HSV-1) gene that encodes for viral thymidine kinase (tk+). Once HSV-1 tk+ is expressed in the target (cancer) cell, therapy can be effected by the administration of a highly molecularly-targeted and systemically non-toxic antiviral drug such as ganciclovir. The development of radiodiagnostic imaging in gene therapy will be reviewed, using HSV-1 tk+ and radioiodinated IVFRU as a basis for development of the theme. Molecular targets that could be exploited in gene therapy, other than tk+, will be identified

  6. Development of radiopharmaceutical for radiosinovectomy; Desenvolvimento de radiofarmaco para radiosinovectomia

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Renata Martinussi

    2009-07-01

    Radiopharmaceuticals prepared with different radionuclides have been used in diagnostic and therapeutic procedures in Nuclear Medicine. The interest in radionuclidic therapy has been increased in last years, with the introduction of new radiopharmaceuticals applied in the destruction of specific cells or to prevent its undesired proliferation. Radiosinovectomy (RSV) is a therapeutic modality that uses radiopharmaceuticals administered in the intra-articular cavity and represents an alternative to the treatment of different arthropaties and, in particular, the arthropaties derived from rheumatoid arthritis and haemophilic. The objective of the present work was to study the labeling of compounds with {sup 90}Y and {sup 177}Lu in order to improve the production conditions and quality control procedures, study the stability of the labeled compounds and preliminary biodistribution studies of the radiopharmaceuticals with potential for RSV applications. The study of the production of {sup 90}Y citrate colloid ({sup 90}Y-Cit) was based in a labeling procedure using {sup 90}Y Cl{sub 3} solution (37 - 54 MBq) that was previously dried, followed by the addition of yttrium nitrate and sodium citrate in p H 7 at 37 deg C for 30 minutes. The production of hydroxyapatite (HA) labeled with {sup 90}Y was based in a labeling procedure using mono hydrated citric acid, yttrium nitrate and {sup 90}Y Cl{sub 3} solution (37 - 370 MBq). The reaction mixture was incubated for 30 minutes at room temperature and the HA was introduced in aqueous medium and the reaction proceed for 30 minutes under strong stirring. {sup 177}Lu-HA was produced using {sup 177}Lu Cl{sub 3} solution (296 MBq), in presence of lutetium oxide in NaCl medium, p H 7, under continuous stirring for 30 minutes at room temperature. Several reaction parameters were studied for the three radiopharmaceuticals. Labeling yield was determined after particles were centrifuged and washed with NaCl 0,9%. Radiochemical purity was

  7. {sup 18}F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type

    Energy Technology Data Exchange (ETDEWEB)

    Balogova, Sona [Comenius University and St. Elisabeth Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Talbot, Jean-Noel; Michaud, Laure; Huchet, Virginie; Kerrou, Khaldoun; Montravers, Francoise [Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Nataf, Valerie [Hopital Tenon, AP-HP, Department of Radiopharmacy, Paris (France)

    2013-06-15

    6-Fluoro-({sup 18}F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, {sup 123}I-metaiodobenzylguanidine (MIBG) and {sup 111}In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for {sup 123}I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as

  8. Public exposure due to the transport of radiopharmaceuticals; Exposicao do publico devido ao transporte de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Demerval L.; Carneiro, Janete C.G.G.; Sanches, Matias P.; Sordi, Gian Maria A.A., E-mail: dlrodri@ipen.b, E-mail: janetegc@ipen.b, E-mail: msanches@ipen.b, E-mail: gsordi@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-10-26

    This paper estimate the radiological impact resulting from radiopharmaceuticals transport from the IPEN to some destinations defined a priori. So, doses were estimated in the public individuals, which are in the streets and vehicles that transit near the public transport, alongside the itinerary went through by packages, during the realization of radiopharmaceuticals transport

  9. Comparative study of radiopharmaceuticals as radiodiagnostic agent of cardiac damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Gil V, M.C.; Mena T, P. (Comision Chilena de Energia Nuclear, Santiago. Dept. de Aplicaciones de los Isotopos y Radiaciones); Gallego H, R.; Mendoza A, J. (Chile Univ., Santiago. Facultad de Ciencias Agrarias, Veterinarias y Forestales)

    1984-04-01

    Cardiac uptake studies with six radiopharmaceuticals have been performed at different time intervals, after to induce cardiac damage in rats as biological model. Phosphorous radiopharmaceuticals sup((99m) Tc-MDP and sup(113m) In-EDTMP) and /sup 197/Hg-MPG possessed the higher cardiac uptake compared with sup(99m) Tc-GH and sup(99m) Tc-DMSA.

  10. Validation of the limulus amebocyte lysate (LAL) test for routine PET radiopharmaceuticals.

    Science.gov (United States)

    Zijlstra, S; Gerken, P; Rechin, C; Wortmann, R; Notohamiprodjo, G

    1997-01-01

    The kinetic turbidimetric limulus amebocyte lysate test was validated as method for detecting endotoxins in short-lived radiopharmaceutical samples. Using this method, radiopharmaceuticals can be released for administration to humans after the test, without extensive loss of radioactivity. Inhibition or enhancement on the LAL results by the product samples were examined in more detail and eliminated.

  11. Quality assurance of radiopharmaceuticals. Radiopharmacy and Quality Control Pharmacists Subcommittees of the Regional Pharmaceutical Officers Committee.

    Science.gov (United States)

    1994-11-01

    This paper describes a level of quality assurance deemed to be acceptable for the preparation of radiopharmaceuticals within hospitals in the UK. It is not intended to give detailed methodology or guidance on premises or procedures, but to give general guidance which can be tailored to meet local needs. It is hoped that a high standard of radiopharmaceutical preparation will be maintained nationwide.

  12. Radiopharmaceutical preparation in-house vs. central radiopharmacy: a make/buy decision.

    Science.gov (United States)

    Cope, R H

    1987-03-01

    Under DRG reimbursement it is essential that all operational costs be considered as targets for reduction. In this article, the author presents a methodology for determining whether to prepare radiopharmaceuticals in house or purchase them from a central radiopharmacy. By using this methodology, purchasing agents may find it possible to save up to 50% of the cost of radiopharmaceuticals.

  13. Recent Progress toward Microfluidic Quality Control Testing of Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Noel S. Ha

    2017-11-01

    Full Text Available Radiopharmaceuticals labeled with short-lived positron-emitting or gamma-emitting isotopes are injected into patients just prior to performing positron emission tomography (PET or single photon emission tomography (SPECT scans, respectively. These imaging modalities are widely used in clinical care, as well as in the development and evaluation of new therapies in clinical research. Prior to injection, these radiopharmaceuticals (tracers must undergo quality control (QC testing to ensure product purity, identity, and safety for human use. Quality tests can be broadly categorized as (i pharmaceutical tests, needed to ensure molecular identity, physiological compatibility and that no microbiological, pyrogenic, chemical, or particulate contamination is present in the final preparation; and (ii radioactive tests, needed to ensure proper dosing and that there are no radiochemical and radionuclidic impurities that could interfere with the biodistribution or imaging. Performing the required QC tests is cumbersome and time-consuming, and requires an array of expensive analytical chemistry equipment and significant dedicated lab space. Calibrations, day of use tests, and documentation create an additional burden. Furthermore, in contrast to ordinary pharmaceuticals, each batch of short-lived radiopharmaceuticals must be manufactured and tested within a short period of time to avoid significant losses due to radioactive decay. To meet these challenges, several efforts are underway to develop integrated QC testing instruments that automatically perform and document all of the required tests. More recently, microfluidic quality control systems have been gaining increasing attention due to vastly reduced sample and reagent consumption, shorter analysis times, higher detection sensitivity, increased multiplexing, and reduced instrumentation size. In this review, we describe each of the required QC tests and conventional testing methods, followed by a

  14. Imaging of neuroendocrine tumours with gamma-emitting radiopharmaceuticals.

    Science.gov (United States)

    Bombardieri, E; Coliva, A; Maccauro, M; Seregni, E; Orunesu, E; Chiti, A; Lucignani, G

    2010-02-01

    Nuclear medicine can image some tumors by means of receptor specific radiopharmaceuticals, and offers the possibility to characterize cancer through the detection of its receptor expression. This is the case of neuroendocrine tumours (NETs), that are visualized by different radiolabelled somatostatin analogues that bind 5 distinct somatostatin receptor types (named sstr1-5) that show different tissue distribution. The subtypes sstr2 and sstr5 are the most commonly expressed in NETs. Until now the most widely used radiolabelled somatostatin analogue for planar and single photon emission computed tomography (SPECT) has been [(111)In]pentetreotide, because of its commercial availability. Other analogues labelled with gamma emitting radionuclides are [(99m)Tc]EDDA/HYNIC-TOC, [(99m)Tc]P829, [(111)In]DOTA-lanreotide, [(111)In]DOTA-NOC-ATE, [(111)In]DOTA-BOC-ATE. However, these compounds have not been successful for the routine use. Moreover, NETs express various receptors that can be depicted by different radiopharmaceuticals, such as [(123)I]VIP and [(111)In]GLP-1. Besides this, some precursors of the catecholamines metabolism, as meta-iodo-benzyl-guanidine (MIBG), labelled with (123)I or (131)I, accumulates in neuroendocrine tissues, in particular those of sympathoadrenal lineage. MIBG scintigraphy is currently indicated for neuroblastoma, paraganglioma and phaeocromocitoma. An impressive technological progress has been achieved recently with PET and, in particular, with the development of hybrid instrumentations (PET/CT) combining nuclear imaging with radiological imaging providing both functional and morphologic information. Among positron emitting tracers, the [(18)F]FDG is the most diffuse in oncology, but other more effective tracers are available for NETs, such as the analogues labelled with 68Ga. The diagnostic sensitivity and accuracy of these technology is superior to that of gamma emitting radiopharmaceuticals, but the fact that they are not still registered

  15. Profile of MIBI Liquid Phase Radiopharmaceutical for Myocardial Imaging

    Directory of Open Access Journals (Sweden)

    I. Daruwati

    2016-04-01

    Full Text Available The 99mTc-MIBI radiopharmaceutical has been used innuclear medicine in Indonesia for myocardial imaging. BATAN researchers have mastered the technology to manufacture MIBI as a liophylized kit. A reformulation of MIBI radiopharmaceutical has been conducted to improve the stability of the kit especially in the liquid-phase kit. Basically, radiopharmaceuticals in liquid form are not different from the dry kit. However in the manufacturing of liquid-phase kit, lyophilization process was not done. To improve the stability of liquid kit, a reformulation of the components was conducted by using two separate vials (Formulation 2 and the characteristics were compared with the one-vial formulation (Formulation 1.The MIBI Formulation 2 consists of two vials, vial A containing 0.06 mg of SnCl2 2H2O and 2.6 mg Sodium Citrate 2H2O and vial B containing 0.5 mg of [Cu(MIBI4]BF4, 1 mg of cysteine hydrochloride, and 20 mg of mannitol.The purposes of this study wereto determine the stability of two different formulations of MIBI as a liquid-phase kit, to compare theirstability in different storage condition such as in refrigerator and freezer, and to compare the ratio of activities attained between target and nontargetorgans after injection to animal model. As a diagnostic agent, MIBI was reconstituted with Technetium-99m as radionuclide tracer to 99mTc-MIBI labeled compound. The radiochemical purity of 99mTc-MIBI was determined by chromatography method using alumina thin-layer chromatography paper as the stationary phase and ethanol 95% as the mobile phase. The results showed MIBI Formulation 2 has a higher stability than Formulation 1. Formulation 2 also maintaineda 96.68%radiochemical purity under 52-day storage and attainedatarget-to-nontarget activity ratio of 8.22.

  16. Stabilization of Tc-99m radiopharmaceuticals by chemical additives (NOTE

    Directory of Open Access Journals (Sweden)

    NADEZDA VUKICEVIC

    2001-09-01

    Full Text Available The reliability and applicability of the preparation of the three, for nuclear medicine very important, 99mTc-radiopharmaceuticals from the inactive (technetium-cold kit solutions were tested. Each examined commercial kit was dissolved in saline (0.9 % NaCl. The conditions of the storage of the inactive kit solutions till labeling were examined. The main problem is the stablity of the reductant stannous ions which is very difficult to predict. To stabilize and ensure a good quality of the labeled radiopharmaceuticals, ascorbic or gentisic acid were added. It was found that the best results were obtained by keeping the samples frozen at –20 ?C. Both stabilizers can be used but for an effective protection much lower concentrations of ascorbic acid are needed. Its concentrations of 12–60 mg/ml of the kit, stabilized dimercaptosuccinate (DMS and pyrophosphate (PyP for about 7–8 days. The solution of 2,3-dicarboxypropane-1,1-diphosphonate (DPD was found to be stable even without the stabilizer. This could be attributed probably to the chemical nature of this complex. However, in routine praxis the applied procedure demands great care and personel very experienced in radiopharmacy.

  17. Current Status of Radiopharmaceuticals for the Theranostics of Neuroendocrine Neoplasms

    Directory of Open Access Journals (Sweden)

    Melpomeni Fani

    2017-03-01

    Full Text Available Abstract: Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs. Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr, other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them. The Glucagon-Like Peptide-1 Receptor (GLP-1R is highly expressed in benign insulinomas, the Cholecystokinin 2 (CCK2/Gastrin receptor is expressed in different NENs, in particular medullary thyroid cancer, and the Glucose-dependent Insulinotropic Polypeptide (GIP receptor was found to be expressed in gastrointestinal and bronchial NENs, where interestingly, it is present in most of the sstr-negative and GLP-1R-negative NENs. Also in the field of sstr targeting new discoveries brought into light an alternative approach with the use of radiolabeled somatostatin receptor antagonists, instead of the clinically used agonists. The purpose of this review is to present the current status and the most innovative strategies for the diagnosis and treatment (theranostics of neuroendocrine neoplasms using a cadre of radiolabeled regulatory peptides targeting their receptors.

  18. Development and clinical application of peptide-based radiopharmaceuticals.

    Science.gov (United States)

    Gotthardt, M; Boermann, O C; Behr, T M; Béhé, M P; Oyen, W J G

    2004-01-01

    Peptide-based radiopharmaceuticals have been introduced into clinical work more than a decade ago. The first and most successful imaging agent to date is the somatostatin analog octreotide. It is used for somatostatin receptor scintigraphy and also receptor-mediated peptide-radiotherapy of neuroendocrine tumors. For in vivo use as radiopharmaceutical, the natural peptide is modified in order to enhance the metabolic stability and to allow stable labeling with a so-called residualizing label. This means, that a radiometal chelator complex bound to a modified peptide stable in serum is internalized into the target cells via a specific receptor. The peptide then undergoes lysosomal degradation leaving the radiometal-chelator complex trapped inside the cell, leading to a high target to background ratio. The successful development of new radiopeptides is thus dependent on modifications of a given natural peptide while preserving the binding affinity for the target receptor(s) at the same time. Other peptides than somatostatin are under development for use as radiopeptides such as Minigastrin, GLP-1, VIP, Substance P, or Neurotensin. Some show very favorable results in clinical trials, like Minigastrin for example. Furthermore, there is increasing interest in peptide-binding sites other than the "classical" receptors for regulatory peptides specifically over-expressed by (neuroendocrine) tumors. In this paper, we provide an overview of the biochemical and radiochemical aspects of radiopeptide development, the current state of clinical use of radiopeptides for diagnosis and therapy of tumors, the current state of development of new compounds, and future developments.

  19. HPLC-MS technique for radiopharmaceuticals analysis and quality control

    Science.gov (United States)

    Macášek, F.; Búriová, E.; Brúder, P.; Vera-Ruiz, H.

    2003-01-01

    Potentialities of liquid chromatography with mass spectrometric detector (MSD) were investigated with the objective of quality control of radiopharmaceuticals; 2-deoxy-2-[18F]fluoro-D-glucose (FDG) being an example. Screening of suitable MSD analytical lines is presented. Mass-spectrometric monitoring of acetonitrile— aqueous ammonium formate eluant by negatively charged FDG.HCO2 - ions enables isotope analysis (specific activity) of the radiopharmaceutical at m/z 227 and 226. Kryptofix® 222 provides an intense MSD signal of the positive ion associated with NH4 + at m/z 394. Expired FDG injection samples contain decomposition products from which at least one labelled by 18F and characterised by signal of negative ions at m/z 207 does not correspond to FDG fragments but to C5 decomposition products. A glucose chromatographic peak, characterised by m/z 225 negative ion is accompanied by a tail of a component giving a signal of m/z 227, which can belong to [18O]glucose; isobaric sorbitol signals were excluded but FDG-glucose association occurs in the co-elution of separation of model mixtures. The latter can actually lead to a convoluted chromatographic peak, but the absence of 18F makes this inconsistent. Quantification and validation of the FDG component analysis is under way.

  20. Radiopharmaceuticals for the therapy of metastatic bone pain

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medicine School, Daegu (Korea, Republic of)

    2006-04-15

    Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. It occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and is complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesion. {sup 32}P, {sup 89}SrCl, {sup 153}Sm-EDTMP, {sup 188}Re/{sup 186}Re-HEDP, and {sup 177}Lu-EDTMP can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic from of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and in some studies, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article

  1. Technetium-99m nitrido radiopharmaceuticals with unprecedented biological properties

    Directory of Open Access Journals (Sweden)

    Adriano Duatti

    2002-09-01

    Full Text Available The chemical methods for the production of technetium-99m radiopharmaceuticals containing a terminal TcºN triple bond have been established more than a decade ago. From that time, the chemistry of nitrido Tc-99m complexes has provided a highly efficient tool for the design and preparation of novel classes of diagnostic agents, and a number of potentially useful radiopharmaceuticals have been discovered. In particular, nitrido technetium-99m tracers have been developed for heart perfusion imaging. In this short review, the chemical and biological properties of the neutral myocardial perfusion tracer bis(N-ethoxy, N-ethyl-dithiocarbamato nitrido Tc-99m (TcN-NOEt will be summarized along with the preparation and preliminary biological evaluation of the first class of monocationic nitrido technetium-99m radiopharmaceuticals exhibiting improved biodistribution properties closer to those expected for an ideal perfusion imaging agent.Os métodos químicos para produção de radiofármacos marcados com tecnécio-99m contendo a ligação tripla terminal TcºN foram estabelecidos há mais de uma década. Desde esta época, a química dos complexos nitridos marcados com 99mTc tem sido uma ferramenta altamente eficiente para o desenho e preparo de novas classes de agentes para diagnóstico e, foi descoberto um número de radiofarmacos potencialmente úteis. Nesta pequena revisão, as propriedades biológicas e químicas do traçador para perfusão miocárdica neutra, o bis(N-etoxi, N-etil-ditiocarbamato nitrido 99mTc (TcN-NOEt, serão resumidas junto com o preparo e avaliação biológica preliminar da primeira classe de radiofármacos nitrido monocatiônico marcado com tecnécio-99m que exibe melhores propriedades em relação à biodistribuição, mais próximas daquelas esperadas para um agente perfusor ideal para imagens.

  2. A method to assess safety and resilience in radiopharmaceuticals production process.

    Science.gov (United States)

    Grecco, Cláudio H S; Vidal, Mario C R; Santos, Isaac J A L; Carvalho, Paulo V R

    2012-01-01

    Radiopharmaceuticals are radiation-emitting substances used in medicine for radiotherapy and imaging diagnosis. A Research Institute, located in Rio de Janeiro, produces three radiopharmaceuticals: the sodium iodate is used in the diagnosis of thyroid dysfunctions, the meta-iodo-benzylguanidine is used in the diagnosis of cardiac diseases, and the fluordesoxyglucose is used in diagnosis in cardiology, oncology, neurology and neuropsychiatry. This paper presents a method to access safety and resilience in radiopharmaceuticals production processes. The method uses resilience indicators in order to proactively evaluate and manage the safety.

  3. Uncertainty sources in radiopharmaceuticals clinical studies; Fontes de incertezas em estudos clinicos com radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Degenhardt, Aemilie Louize; Oliveira, Silvia Maria Velasques de, E-mail: silvia@cnen.gov.br, E-mail: amilie@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    The radiopharmaceuticals should be approved for consumption by evaluating their quality, safety and efficacy. Clinical studies are designed to verify the pharmacodynamics, pharmacological and clinical effects in humans and are required for assuring safety and efficacy. The Bayesian analysis has been used for clinical studies effectiveness evaluation. This work aims to identify uncertainties associated with the process of production of the radionuclide and radiopharmaceutical labelling as well as the radiopharmaceutical administration and scintigraphy images acquisition and processing. For the development of clinical studies in the country, the metrological chain shall assure the traceability of the surveys performed in all phases. (author)

  4. Leading safety performance indicators for resilience assessment of radiopharmaceuticals production process

    Energy Technology Data Exchange (ETDEWEB)

    Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Carvalho, Paulo V.R., E-mail: grecco@ien.gov.b, E-mail: luquetti@ien.gov.b, E-mail: paulov@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Instrumentacao e Confiabilidade Humana; Vidal, Mario C.R., E-mail: mvidal@ergonomia.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEP/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia de Producao. Grupo de Ergonomia e Novas Tecnologias (GENTE)

    2011-07-01

    Radiopharmaceuticals are radiation-emitting substances used in medicine for radiotherapy and imaging diagnosis. A Research Institute, located in Rio de Janeiro, produces three radiopharmaceuticals: the sodium iodate is used in the diagnosis of thyroid dysfunctions, the meta-iodo-benzyl guanidine is used in the diagnosis of cardiac diseases, and the fluorodeoxyglucose is used in diagnosis in cardiology, oncology, neurology and neuro psychiatry. This paper presents a leading safety performance indicators framework to assess the resilience of radiopharmaceuticals production processes. The organizations that use resilience indicators will be able to pro actively evaluate and manage safety. (author)

  5. [Guidelines for radiation protection in medicine--radiopharmaceutical quality control. German Society of Nuclear Medicine].

    Science.gov (United States)

    Brandau, W

    1994-04-01

    For the first time the revision of the "Guideline for radiation protection in medicine" defines extensive quality control procedures for radiopharmaceuticals. The principles of the 99Mo/99mTc-generator, the preparation of 99mTc-radiopharmaceuticals and the origin of the most frequent radiochemical impurities are illustrated. An introduction into the theory of thin layer chromatography is combined with a listing of radiochromatographic systems. This enables the determination of the radiochemical purity of the most important radiopharmaceuticals in clinical routine.

  6. Effect of blood activity on dosimetric calculations for radiopharmaceuticals

    Science.gov (United States)

    Zvereva, Alexandra; Petoussi-Henss, Nina; Li, Wei Bo; Schlattl, Helmut; Oeh, Uwe; Zankl, Maria; Graner, Frank Philipp; Hoeschen, Christoph; Nekolla, Stephan G.; Parodi, Katia; Schwaiger, Markus

    2016-11-01

    The objective of this work was to investigate the influence of the definition of blood as a distinct source on organ doses, associated with the administration of a novel radiopharmaceutical for positron emission tomography-computed tomography (PET/CT) imaging—(S)-4-(3-18F-fluoropropyl)-L-glutamic acid (18F-FSPG). Personalised pharmacokinetic models were constructed based on clinical PET/CT images from five healthy volunteers and blood samples from four of them. Following an identifiability analysis of the developed compartmental models, person-specific model parameters were estimated using the commercial program SAAM II. Organ doses were calculated in accordance to the formalism promulgated by the Committee on Medical Internal Radiation Dose (MIRD) and the International Commission on Radiological Protection (ICRP) using specific absorbed fractions for photons and electrons previously derived for the ICRP reference adult computational voxel phantoms. Organ doses for two concepts were compared: source organ activities in organs parenchyma with blood as a separate source (concept-1); aggregate activities in perfused source organs without blood as a distinct source (concept-2). Aggregate activities comprise the activities of organs parenchyma and the activity in the regional blood volumes (RBV). Concept-1 resulted in notably higher absorbed doses for most organs, especially non-source organs with substantial blood contents, e.g. lungs (92% maximum difference). Consequently, effective doses increased in concept-1 compared to concept-2 by 3-10%. Not considering the blood as a distinct source region leads to an underestimation of the organ absorbed doses and effective doses. The pronounced influence of the blood even for a radiopharmaceutical with a rapid clearance from the blood, such as 18F-FSPG, suggests that blood should be introduced as a separate compartment in most compartmental pharmacokinetic models and blood should be considered as a distinct source in

  7. 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.

  8. A simple and effective technique to reduce staff exposure during the preparation of radiopharmaceuticals

    National Research Council Canada - National Science Library

    Chris Tsopelas; Peter J Collins; Cristina Blefari

    2003-01-01

    In the preparation of radiopharmaceuticals, staff receive considerable radiation exposure to the hands during withdrawal of activity from the elution vial, from a combination of the syringe and elution vial activities...

  9. A Simple and Effective Technique to Reduce Staff Exposure During the Preparation of Radiopharmaceuticals

    National Research Council Canada - National Science Library

    Tsopelas, Chris; Collins, Peter J; Blefari, Cristina

    2003-01-01

    ...: In the preparation of radiopharmaceuticals, staff receive considerable radiation exposure to the hands during withdrawal of activity from the elution vial, from a combination of the syringe and elution vial activities...

  10. UPLC®-RAD the new standard in quality control of PET radiopharmaceutical

    NARCIS (Netherlands)

    Maas, B.; Zijlma, R.; Bannink, A.; Lub-De Hooge, M.; Elsinga, P.H.; Dierckx, R.A.J.O.; Boersma, H.H.; Luurtsema, G.

    2013-01-01

    Objectives: Good Manufacturing Practice (GMP) compliant productions require validated, quality control procedures of the radiopharmaceutical. Quality control of the final product is conventionally performed by High Performance Liquid Chromatography (HPLC) with UV and radioactivity (RAD) detection.

  11. VII. Boettstein Colloquium: PET-Radiopharmaceuticals at PSI: achievement and future prospects

    Energy Technology Data Exchange (ETDEWEB)

    Schubiger, P.A.; Beer, H.F.; Blaeuenstein, P.; Leenders, K.E.

    1993-12-31

    The three sessions of the 1993 Boettstein colloquium dealt with the following topics: - PET-radiopharmaceuticals, - PET-scanning: significance of tracer uptake, - clinical options using PET. 22 papers were presented. figs., refs.

  12. 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.

  13. Pharmaceuticals—Special Issue on Radiopharmaceutical Chemistry between Imaging and Endoradiotherapy

    Directory of Open Access Journals (Sweden)

    Klaus Kopka

    2014-07-01

    Full Text Available The fields of molecular biology, immunology and genetics have generated many important developments that advance the understanding of the induction and progression of oncological, cardiological and neurological diseases as well as the identification of disease-associated molecules and drugs that specifically target diseased cells during therapy. These insights have triggered the development of targeted radiopharmaceuticals which open up a new dimension of radiopharmaceutical sciences in nuclear medicine. Radiopharmaceuticals, also called radiotracers, are radiolabelled molecules, bearing a “radioactive lantern”, and used as molecular probes to address clinically relevant biological targets such as receptors, enzymes, transport systems and others. Positron emission tomography (PET and single photon emission computed tomography (SPECT realised in the en-vogue hybrid technologies PET/CT, SPECT/CT and PET/MRI represent the state-of-the-art diagnostic imaging technologies in nuclear medicine which are used to follow the trace of the administered radiopharmaceutical noninvasively thereby in vivo visualising and assessing biological processes at the subcellular and molecular level in a highly sensitive manner. In this connexion novel radiopharmaceuticals for the noninvasive molecular imaging of early disease states and monitoring of treatment responses in vivo by means of PET/CT, SPECT/CT and PET/MRI are indispensable prerequisites to further advance and strengthen the unique competence of radiopharmaceutical sciences. In the era of personalised medicine the diagnostic potential of radiopharmaceuticals is directly linked to a subsequent individual therapeutic approach called endoradiotherapy. Depending on the “radioactive lantern” (gamma or particle emitter used for radiolabelling of the respective tracer molecule, the field of Radiopharmaceutical Chemistry can contribute to the set-up of an “in vivo theranostic” approach especially in

  14. Metabolic radiopharmaceutical therapy in nuclear medicine; Terapia metabolica mediante radiofarmacos en medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Reguera, L.; Lozano, M. L.; Alonso, J. C.

    2016-08-01

    In 1986 the National Board of Medical Specialties defined the specialty of nuclear medicine as a medical specialty that uses radioisotopes for prevention, diagnosis, therapy and medical research. Nowadays, treatment with radiopharmaceuticals has reached a major importance within of nuclear medicine. The ability to treat tumors with radiopharmaceutical, Radiation selective therapy has become a first line alternative. In this paper, the current situation of the different therapies that are sued in nuclear medicine, is reviewed. (Author)

  15. Gallium-68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience

    OpenAIRE

    Alireza Aslani; Snowdon, Graeme M; Bailey, Dale L; Schembri, Geoffrey P; Bailey, Elizabeth A.; Paul J Roach

    2014-01-01

    Objective(s): Gallium-68 (Ga-68) is an ideal research and hospital-based PET radioisotope. Currently, the main form of Ga-68 radiopharmaceutical that is being synthesised in-house is Ga-68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga-68 DOTATATE. Methods: The automated ...

  16. Evaluation of radiochemical purities of some radiopharmaceuticals in Shiraz Namazi teaching hospital

    OpenAIRE

    Hossein Sadeghpour; Mehrosadat Alavi; Majid Shahedi; Seyed Mohammad Entezarmahdi; Amirhossein Sakhteman

    2015-01-01

    Many radiopharmaceuticals, as a special group of drugs, are eventually prepared at the nuclear medicine departments of the hospitals. Therefore, their quality control procedures such as sterility tests, radionuclide, radiochemical and chemical purity should be carried out in the hospitals. In this study, radiochemical purity for more than 300 preparations of three different radiopharmaceutical formulations from commercial kits were tested using instant thin layer chromatography. The formulati...

  17. Gallium‐68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2014-10-01

    Full Text Available Objective(s: Gallium‐68 (Ga‐68 is an ideal research and hospital‐based PET radioisotope. Currently, the main form of Ga‐68 radiopharmaceutical that is being synthesised in‐house is Ga‐68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga‐68 DOTATATE. Methods: The automated synthesis system we use is divided into three parts of a servomotor modules, b single use sterile synthesis cassettes and, c a computerized system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in‐. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC‐SG and HPLC methods. Results: A total of 500 Ga‐68 DOTATATE syntheses (>800 patient doses were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga‐68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer’s expected value of approximately 70%. Germanium breakthrough averaged 8.6×10‐6% of total activity which is well below the recommended level of 0.001%. The average ITLC‐measured radiochemical purity was above 98.5% and the average HPLC‐measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. Conclusion: In our experience the automated synthesis system performs reliably with a relatively low incident

  18. Gallium-68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience.

    Science.gov (United States)

    Aslani, Alireza; Snowdon, Graeme M; Bailey, Dale L; Schembri, Geoffrey P; Bailey, Elizabeth A; Roach, Paul J

    2014-01-01

    Gallium-68 (Ga-68) is an ideal research and hospital-based PET radioisotope. Currently, the main form of Ga-68 radiopharmaceutical that is being synthesised in-house is Ga-68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga-68 DOTATATE. The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerised system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in-. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC-SG and HPLC methods. A total of 500 Ga-68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga-68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer's expected value of approximately 70%. Germanium breakthrough averaged 8.6×10(-6)% of total activity which is well below the recommended level of 0.001%. The average ITLC-measured radiochemical purity was above 98.5% and the average HPLC-measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga-68 DOTATATE output with high

  19. Radiopharmaceuticals for diagnosis of inflammation; Radiopharmaka fuer die Entzuendungsdiagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Meller, B.; Baehre, M. [Luebeck Univ. (Germany). Klinik fuer Radiologie und Nuklearmedizin

    2007-06-15

    Inflammations represent mediator-induced reactions of the hematopoetic-immunologic cell system resulting from exogenous or endogenous stimuli. On cellular level, an increased expression of inflammatory genes is followed by the release of several mediators. As inflammatory response vascular permeability increases and interstitial oedema develops. Additionally, white blood cells emigrate and several transduction cascades are activated. Radiopharmaceuticals for inflammation scintigraphy should specifically reflect one or several aspects of inflammation pathophysiology on molecular level. A group of elder tracers for this purpose comprised substances that are accumulated due to the permeability of physiological barriers. However, their property to accumulate in all processes with increased vascular permeability results in a comparably low specificity of these methods. In-vitro-labelled granulocytes were the method of choice for scintigraphic imaging of inflammation for years. Investigations with {sup 111}In-labelled granulocytes are still frequently considered as the gold standard to detect inflammation by scintigraphy. The use of antibodies or antibody fragments directed against leucocytes allowed in vivo labelling and substituted more complex techniques of in vitro labelling despite of several disadvantages. Due to the superior imaging quality of positron emission tomography, [{sup 18}F]FDG-labelled leucocytes might result in a renaissance of in vitro methods. In cases of cerebral inflammation, activated microglia was visualised by its increased expression of benzodiazepin receptors. An interesting approach to differentiate between infection and sterile inflammation could be the use of bacterial gyrase inhibitors labelled with radioactive compounds. At present, specificity of this method is still controversially discussed. In search of substances to visualise inflammatory transduction cascades selectively, several chemotactic and chemokinetic cytokines, metabolites

  20. Activities, procedures and doses in pediatric patients due to radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Silvia Maria Velasques de Oliveira

    2008-12-01

    Full Text Available An investigation performed between 2003 and 2005 in sixteen selected public and private institutions in Northeast, Southeast and South geographical regions of Brazil evaluated average organ doses and effective doses in 2,411 pediatric patients due to diagnostic procedures with radiopharmaceuticals. For 1 year, effective doses were greater than literature. For 5 years, differences were noticed between present work and literature for bone scintigraphy, thyroid scintigraphy and 67Ga citrate scintigraphy. These differences may be attributed to the uncertainties in internal dose calculations. High absorved doses in bone surfaces of children due to 67Ga citrate and bone scintigraphy should be evaluated accordingly. Current protocols used recommend standardized mean activities per mean weight for all ages. However, it was observed that the activities were not standardized and were higher for children with younger ages. Future studies are needed for optimising activities of radiopharmaceuticals to these patients in the country.Foi realizado no Brasil, no período 2003-2005, um estudo sobre doses absorvidas em órgãos e doses efetivas devido ao uso de radiofármacos em pacientes pediátricos. Foram estudadas 2.411 crianças e adolescentes menores de 18 anos. Foi observado que as atividades usadas não foram padronizadas, sendo maiores para crianças de menor idade, podendo ser otimizadas conforme apropriado. Para 1 ano, as doses efetivas foram maiores do que as publicadas na literatura e para 5 anos, foram observadas diferenças para cintilografias ósseas, cintilografias da tireóide, e pesquisas de corpo inteiro com citrato de 67G. Deve ser avaliado se doses absorvidas em órgãos, especialmente para superfície óssea devido a cintilografias ósseas com 99mTc MDP e pesquisa de corpo inteiro com citrato de 67Ga podem acarretar risco radiológico adicional aos pacientes, considerando-se as peculiaridades de seu estado clínico.

  1. Finger doses for staff handling radiopharmaceuticals in nuclear medicine.

    Science.gov (United States)

    Pant, Gauri S; Sharma, Sanjay K; Rath, Gaura K

    2006-09-01

    Radiation doses to the fingers of occupational workers handling 99mTc-labeled compounds and 131I for diagnostic and therapeutic procedures in nuclear medicine were measured by thermoluminescence dosimetry. The doses were measured at the base of the ring finger and the index finger of both hands in 2 groups of workers. Group 1 (7 workers) handled 99mTc-labeled radiopharmaceuticals, and group 2 (6 workers) handled 131I for diagnosis and therapy. Radiation doses to the fingertips of 3 workers also were measured. Two were from group 1, and 1 was from group 2. The doses to the base of the fingers for the radiopharmacy staff and physicians from group 1 were observed to be 17+/-7.5 (mean+/-SD) and 13.4+/-6.5 microSv/GBq, respectively. Similarly, the dose to the base of the fingers for the 3 physicians in group 2 was estimated to be 82.0+/-13.8 microSv/GBq. Finger doses for the technologists in both groups could not be calculated per unit of activity because they did not handle the radiopharmaceuticals directly. Their doses were reported in millisieverts that accumulated in 1 wk. The doses to the fingertips of the radiopharmacy worker and the physician in group 1 were 74.3+/-19.8 and 53.5+/-21.9 microSv/GBq, respectively. The dose to the fingertips of the physician in group 2 was 469.9+/-267 microSv/GBq. The radiation doses to the fingers of nuclear medicine staff at our center were measured. The maximum expected annual dose to the extremities appeared to be less than the annual limit (500 mSv/y), except for a physician who handled large quantities of 131I for treatment. Because all of these workers are on rotation and do not constantly handle radioactivity throughout the year, the doses to the base of the fingers or the fingertips should not exceed the prescribed annual limit of 500 mSv.

  2. Constancy tests and quality assurance of the activimeters used in a radiopharmaceutical production unit

    Energy Technology Data Exchange (ETDEWEB)

    Gontijo, Rodrigo M.G.; Mamede, Marcelo [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Ferreira, Andréa V.; Nascimento, Leonardo T.C.; Costa, Flávia M.; Silva, Juliana B., E-mail: rodrigo.gontijo@cdtn.br, E-mail: mamede.mm@gmail.com [Universidade Federal de Minas Gerais (IMA/FM/UFMG), Belo Horizonte, MG (Brazil). Departamento de Anatomia e Imagem

    2017-07-01

    Activimeters (or dose calibrators) are essential instruments to verify activity of radiopharmaceutical after production and also before the dose administration in humans or animals for molecular imaging. The efficiency and safety measurements depend on, beside other factors, constancy tests and quality assurance. Thereby, the aim of this work was to perform constancy tests and quality assurance in the activimeters of the UPPR/CDTN, based on the CNEN-NN 3.05 Brazilian standard and the manufacturer's manual. Physical inspection, auto zero, background check, camera voltage, data check and constancy test were done. In addition, accuracy and precision tests were performed using a set of standard certified radioactive sources ({sup 57}Co, {sup 133}Ba and {sup 137}Cs), according to the CNEN NN 3.05 Brazilian standard. Linearity test was also performed to evaluate the response of the equipment in over the entire range of activities used in routine. The equipment are periodically submitted to the quality control tests and the results were compared. After performing the proposed tests it is possible to conclude that activimeters are in accordance with the requirements of the CNEN standard and manufacturer's manual. A quality control checklist was prepared to guide users and to record the results of quality assurance testing to monitor the equipment performance. This initiative is part of the quality assurance program implemented at UPPR. (author)

  3. Review on production of 89Zr in a medical cyclotron for PET radiopharmaceuticals.

    Science.gov (United States)

    Kasbollah, Azahari; Eu, Peter; Cowell, Simon; Deb, Pradip

    2013-03-01

    This article is intended to provide an overview of the production and application of (89)Zr for the professional development of nuclear medicine technologists. It outlines the cyclotron targeting, separation and labeling options, and techniques for the preparation of the radionuclide (89)Zr (half-life, 78.4 h [3.3 d]) used in PET. Unlike the commonly used (18)F-FDG, with a 109.7-min half-life, the longer half-life of (89)Zr makes it possible to use high-resolution PET/CT to localize and image tumors with monoclonal antibody radiopharmaceuticals and thus potentially expand the use of PET. This paper briefly reviews the cyclotron technique of (89)Zr production and outlines the range and preparation techniques available for making (89)Y targets as a starting material. It then discusses how cyclotron-produced (89)Zr can be separated, purified, and labeled to monoclonal antibodies for PET/CT of specific tumors. We argue that knowledge and understanding of this long-lived PET radionuclide should be part of the professional development of nuclear medicine technologists because it will lead to better patient outcomes and potentially increase the pool of collaborators in this field of research.

  4. AUTOMATION FOR THE SYNTHESIS AND APPLICATION OF PET RADIOPHARMACEUTICALS.

    Energy Technology Data Exchange (ETDEWEB)

    Alexoff, D.L.

    2001-09-21

    The development of automated systems supporting the production and application of PET radiopharmaceuticals has been an important focus of researchers since the first successes of using carbon-11 (Comar et al., 1979) and fluorine-18 (Reivich et al., 1979) labeled compounds to visualize functional activity of the human brain. These initial successes of imaging the human brain soon led to applications in the human heart (Schelbert et al., 1980), and quickly radiochemists began to see the importance of automation to support PET studies in humans (Lambrecht, 1982; Langstrom et al., 1983). Driven by the necessity of controlling processes emanating high fluxes of 511 KeV photons, and by the tedium of repetitive syntheses for carrying out these human PET investigations, academic and government scientists have designed, developed and tested many useful and novel automated systems in the past twenty years. These systems, originally designed primarily by radiochemists, not only carry out effectively the tasks they were designed for, but also demonstrate significant engineering innovation in the field of laboratory automation.

  5. Estimation of patient dose from radiopharmaceuticals using voxel models.

    Science.gov (United States)

    Petoussi-Henss, Nina; Zankl, Maria; Nosske, Dietmar

    2005-02-01

    The aim of this study was to demonstrate the advantages of patient dosimetry using voxel models and to present sets of dose estimates for patients of different gender and size. These models offer greater realism with respect to organ shape and topology than the well-established Medical Internal Radiation Dose (MIRD)-type mathematical models. At the National Research Centre for Environment and Health (GSF), specific absorbed fractions have been previously calculated for 4 male and 3 female voxel models, representing different age and stature, for a wide range of source organs. For this study, estimates both for established and new radiopharmaceuticals were performed using biokinetic data from International Commission on Radiological Protection (ICRP). The above calculations allowed for comparison to the MIRD technique in relation to the resulting absorbed organ and effective doses. Furthermore, data sets representing a range of voxel phantoms were investigated. It was found that dose differences among the voxel models can amount up to a factor of 3.

  6. In Vitro Assessment of the In Vivo Stability of Cu-64 Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packard, Alan B

    2011-12-15

    Research Plans: The successful development of Cu-64 radiopharmaceuticals depends upon retention of the Cu-64 atom in the radiopharmaceutical. To date, the focus has been on the development of chelators that better retain Cu-64, but there has been no effort to develop an effective method by which improved retention may be measured. In the absence of a suitable analytical method, the stability of Cu-64 radiopharmaceuticals is estimated indirectly, with decreased liver uptake suggesting higher in vivo complex stability. But this approach is inadequate for radiopharmaceuticals, such as radiolabeled antibodies, that are expected to accumulate in the liver even when there is no free Cu-64 present. The absence of such a method has also hampered efforts to systematically evaluate the chemical factors that may give rise to improved retention. The objective of this project is to develop and validate such a method. Accomplishments: The two primary accomplishments of this project will be 1) the development and validation of a method to measure the stability of Cu-64 radiopharmaceuticals and 2) the determination of the chemical factors that define the in vivo stability of Cu 64 radiopharmaceuticals. Because Cu(II) is extremely labile, the in vivo stability of Cu-64 radiopharmaceuticals is not primarily determined by the amount of free Cu that is present at any given time or by the thermodynamic stability constants, but rather by the rate at which Cu is lost from the complex, the dissociation rate constant, kd. The dissociation rate constants of the Cu-64 complexes from a series of bifunctional chelators (BFCs) will be measured using Free Ion Selective Radiotracer Extraction (FISRE), a technique originally developed to measure bioavailable Cu in environmental samples. FISRE will also be applied to the determination of the kd's of a series of reference Cu-64 complexes to determine the chemical factors that define the in vivo stability of Cu-64 radiopharmaceuticals. Potential

  7. Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals : a concise overview and practical guidance for a risk-based approach

    NARCIS (Netherlands)

    Lange, Rogier; ter Heine, Rob; Decristoforo, Clemens; Penuelas, Ivan; Elsinga, Philip H.; van der Westerlaken, Monique M. L.; Hendrikse, N. Harry

    Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations

  8. Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: a concise overview and practical guidance for a risk-based approach

    NARCIS (Netherlands)

    Lange, R.; Heine, R. ter; Decristoforo, C.; Penuelas, I.; Elsinga, P.H.; Westerlaken, M.M. van der; Hendrikse, N.H.

    2015-01-01

    Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations

  9. Alternative methods for radiochemical purity testing in radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Ideli M. de; Martins, Patricia de A.; Silva, Jose L. da; Ramos, Marcelo P.S.; Lima, Jose A.S.; Pujatti, Priscilla B.; Fukumori, Neuza T.O.; Matsuda, Margareth M.N. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The radiochemical purity (RCP) testing is as prerequisite for radiopharmaceuticals before the administration to the patient. Because time is critical in nuclear medicine, emphasis should be given to the radiochemical quality control procedures, in order to obtain the maximum amount of information in the minimum period of time. Radiochemical purity is defined as the proportion of the total radioactivity in the product that is present in the specified chemical form. Usually, the RCP is evaluated by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The most widely used technique for RCP determination in radiopharmaceutical preparations is TLC-aluminium (TLC-Al), instant thin layer chromatography-silica gel (ITLC-SG) and paper chromatography (PC). Indeed, many of the pharmacopeial methods use these techniques. The purpose of the present study was to evaluate different chromatographic systems for RCP in {sup 67}Ga-Citrate, {sup 111}In-Octreotide, {sup 177}Lu-DOTATATE and {sup 153}Sm-HA. PC was performed with 3MM/1MM Whatman plates, TCL-Al sheets from Merck and ITLC-SG sheets from Pall Corporation and Varian Inc. The mobile phases were 0.16 mol.L{sup -1} sodium acetate, 0.9% sodium chloride (p/v), 0.1 mol.L{sup -1} sodium citrate buffer, 0.2 mol.L{sup -1} EDTA, methanol:0.4 mol.L{sup -1} ammonium acetate (1:1) mixture, and pyridine:ethanol:water (1:2:4) mixture. The samples were placed on plates in triplicate and immediately put into pre-saturated chambers with the mobile phase. After the chromatographic separation, the plates were dried and cut into 7, 10 or 12 segments and each one was separately measured in a gamma counter during 0.20 minutes (set on the radioisotope window). The results in the gamma counter were expressed in counts per minute (cpm). The chromatographic systems for {sup 177}Lu-DOTATATE and {sup 153}Sm-HA gave the best performances in 0.1 mol L{sup -1} sodium citrate buffer/TLC-Al and 0.9% (p/v) sodium chloride

  10. Comparison of radiochemical purity control methods for 99Tcm radiopharmaceuticals used in hospital radiopharmacies.

    Science.gov (United States)

    Mallol, J; Bonino, C

    1997-05-01

    The free fraction of pertechnetate in 99Tcm radiopharmaceuticals has to be tested for quality control reasons in line with the European Pharmacopoeia. Such quality control is often performed by miniaturized chromatographic methods. There are several recommended methods in the literature for quality control of the same radiopharmaceuticals, though it is unlikely that all methods are equivalent. Some of these methods were compared, taking into account different parameters (spot size, time required, analytical artifacts, true separation and shape of the chromatographic peaks, ease of handling), to verify the best method for the control of each radiopharmaceutical. It would appear that instant thin layer chromatography silica gel is the best support for these miniaturized methods, using MEK as solvent to check DTPA, DMSA, gluconate, pyrophosphate, medronate and phytate; NaCl 20% solution is the best solvent for IDA derivatives, human albumin and albumin particles (microspheres, macroaggregates).

  11. Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Missailidis, Sotiris [The Open University, Milton Keynes (United Kingdom). Dept. of Chemistry and Analytical Sciences]. E-mail: s.missailidis@open.ac.uk; Perkins, Alan [University of Nottingham (United Kingdom). Dept. of Medical Physics; Santos-Filho, Sebastiao David; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria

    2008-12-15

    In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects. (author)

  12. [Radioisotopic imaging of neuroendocrine tumours. Which radiopharmaceutical and which diagnostic procedure?].

    Science.gov (United States)

    Bombardieri, E; Maccauro, M; Castellani, M R; Chiti, A; Procopio, G; Bajetta, E; Seregni, E

    2001-12-01

    Neuroendocrine tumours can be visualized by several nuclear medicine modalities based on different mechanisms of cellular uptake. The most widely used radiopharmaceutical are the metaiodobenzylguanidine (123I/131I MIBG) and pentetreotide (111In pentetreotide). The first tracer follows the metabolic pathway of norephinephrine while the second one binds to somatostatin receptors which are expressed with high intensity on the neuroendocrine tissue. Some radiopharmaceuticals (Anti-CEA, Anti-CgA, Anti-GD2 monoclonal antibodies) have today only an experimental value, others such as 99mTc(V)DMSA had in the past very limited indications (medullary thyroid cancer) but at present their production is going to be stopped. An interesting series of new peptides showing a great affinity for the receptors/structures expressed by the neuroendocrine tissue is under evaluation in order to obtain a better tumour specificity. Among the positron-emitting radiopharmaceuticals, the 18F-fluorodeoxyglucose (FDG), in spite it is considered the most widely used tracer for clinical PET in oncology, did not show a satisfactory uptake in the well differentiated neuroendocrine tissues. On the contrary 18F-FDG is the best radiopharmaceutical to visualize those rare poorly differentiated neurondocrine tumours with a high proliferative index. For this reason also in this area, new radiopharmaceuticals have been studies and developed. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. Another radiopharmaceutical in development for PET is 11C L-DOPA which seems to be useful in visualizing endocrine pancreatic tumours. 18F-DOPA whole body PET may be a more promising imaging approach. Aim of this review is to summarize the potential of nuclear medicine techniques in the diagnosis of neuroendocrine tumours and to stresses the renewed role of nuclear medicine in the management of this disease.

  13. Radiopharmaceuticals for diagnosis. [Final] report, 1 January 1991--31 December 1993

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, D.E.

    1993-06-01

    Since 1987, this grant has supported the development of new radiochemical methods for use with short-lived, positron-emitting radionuclides; new laboratory techniques for radiochemical syntheses; and development of new radiopharmaceuticals which will be of use in Positron Emission Tomography. For the period 1 January 1991 to 31 December 1993, the authors have continued their efforts in all of these areas, as they feel that an integrated approach to the synthesis and characterization of new PET Radiopharmaceuticals is crucial to the continued growth and application of this imaging technique in modern medicine. Progress in a number of these areas is described in this report.

  14. Mathematical Simulation of Transport Kinetics of Tumor-Imaging Radiopharmaceutical 99mTc-MIBI

    Directory of Open Access Journals (Sweden)

    O. N. Shevtsova

    2017-01-01

    Full Text Available The proposed model describes in a quality way the process of tumor-imaging radiopharmaceutical Tc99m-MIBI distribution with taking into account radiopharmaceutical accumulation, elimination, and radioactive decay. The dependencies of concentration versus the time are analyzed. The model can be easily tested by the concentration data of the radioactive pharmaceuticals in the blood measured at early time point and late time point of the scanning, and the obtained data can be used for determination of the washout rate coefficient which is one of the existing oncology diagnostics methods.

  15. Determination and reliability of dose coefficients for radiopharmaceuticals; Ermittlung der Zuverlaessigkeit von Dosiskoeffizienten fuer Radiopharmaka

    Energy Technology Data Exchange (ETDEWEB)

    Spielmann, V.; Li, W.B.; Zankl, M.; Oeh, U.

    2015-11-15

    The dose coefficients used in nuclear medicine for dose calculations of radiopharmaceuticals are based on recommendations by ICRP (International Commission on radiological protection) and the MIRD (Medical Internal Radiation Dose Committee) using mathematical models for the temporal activity distributions in organs and tissues (biokinetic models) and mathematical models of the human body. These models using an idealized human body do not include uncertainty estimations. The research project is aimed to determine the uncertainties and thus the reliability of the dose coefficients for radiopharmaceuticals and to identify the biokinetic and dosimetric parameters that contribute most of the uncertainties.

  16. A 3D high-resolution gamma camera for radiopharmaceutical studies with small animals

    CERN Document Server

    Loudos, G K; Giokaris, N D; Styliaris, E; Archimandritis, S C; Varvarigou, A D; Papanicolas, C N; Majewski, S; Weisenberger, D; Pani, R; Scopinaro, F; Uzunoglu, N K; Maintas, D; Stefanis, K

    2003-01-01

    The results of studies conducted with a small field of view tomographic gamma camera based on a Position Sensitive Photomultiplier Tube are reported. The system has been used for the evaluation of radiopharmaceuticals in small animals. Phantom studies have shown a spatial resolution of 2 mm in planar and 2-3 mm in tomographic imaging. Imaging studies in mice have been carried out both in 2D and 3D. Conventional radiopharmaceuticals have been used and the results have been compared with images from a clinically used system.

  17. New radiopharmaceuticals for receptor scintigraphy and radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Virgolini, I.; Traub, T.; Leimer, M.; Novotny, C.; Pangerl, T.; Ofluoglu, S.; Halvadjieva, E.; Smith-Jones, P.; Flores, J.; Li, S.R.; Angelberger, P.; Havlik, E.; Andreae, F.; Raderer, M.; Kurtaran, A.; Niederle, B.; Dudczak, R. [Vienna Univ., Vienna (Austria). Dept. of Nuclear Medicine

    2000-03-01

    In vitro data have demonstrated a high amount of receptors for various hormones and peptides on malignant cells of neuroendocrine origin. Among these, binding sites for member of the SST-family (hSSTR1-5) are frequently found, and their expression has led to therapeutic and diagnostic attempts to specifically target these receptors. Receptor scintigraphy using radiolabeled peptide ligands has proved its effectiveness in clinical practice. In addition, initial results have indicated a clinical potential for receptor-targeted radiotherapy. Based on somatostatin (SST) receptor (R) recognition, the novel radiopharmaceuticals {sup 111}In/{sup 9}0Y-DOTA-lanreotide developed at the University of Vienna as well as {sup 111}In/{sup 9}0Y-DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide (NOVARTIS) both have provided promising data for diagnosis and treatment of hSSTR-positive tumors. SSTR scintigraphy using {sup 111}In-DTPA-DPhe{sup 1}-octreotide has a high positive predictive value for the vast majority of neuroendocrine tumors and has gained its place in the diagnostic work-up as well as follow-up of patients. Here it was used {sup 111}In-DOTA-lanreotide scintigraphy in 166 patients since 1997 and have seen positive results in 93% of patients. In 42 patients with neuroendocrine tumors comparative data were obtained. As opposed to {sup 111}In-DTPA-DPhe{sup 1}-octreotide and {sup 111}In-DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide, discrepancies in the scintigraphic results were seen in about one third of patients concerning both the tumor uptake as well as tumor lesion detection. Initial results both with {sup 9}0Y-DOTA-lanreotide as well as {sup 9}0Y-DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide has pointed out the clinical potential of radionuclide receptor-targeted radiotherapy. This new therapy could offer palliation and disease control at a reduced cost. The final peptide therapy strategy is most probably cheaper than conventional radio therapies or prolonged chemo therapies. Overall

  18. Obligations, precautions and pending issues in regulatory development for radiopharmaceuticals in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Gamboa, Maryelle Moreira Lima; Roesch, Heveline Rayane Moura; Lemos, Vanessa Pinheiro Amaral, E-mail: maryellelg@hotmail.com [PPG BioSaude, Universidade Luterana do Brasil, Canoas, RS (Brazil); Rocha, Bruna Oliveira [Faculty of Biology, Universidade Luterana do Brasil, Canoas, RS (Brazil); Santos-Oliveira, Ralph [Institute of Radiopharmacy Research, Universidade Estadual da Zona Oeste, Rio de Janeiro, RJ (Brazil)

    2014-04-15

    Radiopharmaceuticals are compounds that have a radionuclide and may be gamma-radiation emitter (γ) or positrons emitter (β+), linked to a molecule with specific diagnostic and therapeutic purposes. The progress in the use of radiopharmaceuticals has culminated to a sector in common with other types of drugs: regulation and surveillance. >From 2006 on, production, marketing and use of these drugs were open to the Brazilian market granting much more freedom due to the Constitutional Amendment 49, resulting from the previous Constitutional Amendment 199/03 which removes the Union monopoly for this kind of manipulation and granted this production to other nuclear medicine. From this date on, the amount of this type of sold product have been greatly increased, and the nucleus of surveillance and regulation in Brazil have also advanced in the legislative processes, creating documents that are now more focused on radiopharmaceuticals in the national territory (Resolutions No. 63 and No. 64). In international overview, there is too much to be done in regulatory terms in Brazil, such as adding mainly issues of drugs surveillance to pharmacovigilance practice in radiopharmaceuticals drugs. (author)

  19. Studies on clinical standard. Studies on the standardization of clinical application of novel radiopharmaceuticals for circulation

    Energy Technology Data Exchange (ETDEWEB)

    Sugishita, Yasuro [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Kanbara, Hirofumi; Konishi, Junji [and others

    1998-08-01

    This paper is a summary guideline for the use of recent radiopharmaceuticals for circulation in various disease states, which is based on the studies to recognize the actual status of the use of radiopharmaceuticals by questionnaire, then to make the guideline for their use by authors and finally to evaluate its usefulness. The questionnaire to 339 facilities was performed in 1995 to obtained answers from 200 facilities, of which 96% had used at least one of the novel radiopharmaceuticals. Planar and SPECT imaging had been done under various conditions in those facilities. This guideline consists of three chapters. In the chapter for the tracer, use of radiopharmaceuticals, theory, apparatuses, technique, diagnostic criteria and notes for diagnosis were guided for {sup 123}I-BMIPP (myocardial imaging), {sup 123}I-MIBG (myocardial imaging) and {sup 99m}Tc-MIBI and -TF (blood flow imaging). In the chapter for disease states, pathophysiology of following diseases and significance of nuclear medicine in their diagnosis, therapy and prognosis were described: acute coronary diseases, myocardial infarction, angina pectoris, cardiomyopathy and others. In the additional chapter, {sup 111}In-labeled anti-myosin antibody was described for imaging of impaired myocardium. The present guideline was hoped to be useful. (K.H.). 315 refs.

  20. Harvard-MIT research program in short-lived radiopharmaceuticals. Technical progress report, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.

    1991-12-31

    This report presents research on radiopharmaceuticals. The following topics are discussed: antibody labeling with positron-emitting radionuclides; antibody modification for radioimmune imaging; labeling antibodies; evaluation of technetium acetlyacetonates as potential cerebral blood flow agents; and studies in technetium chemistry. (CBS)

  1. Fluorine-18 radiopharmaceuticals beyond [F-18]FDG for use in oncology and neurosciences

    NARCIS (Netherlands)

    Coenen, H. H.; Elsinga, P. H.; Iwata, R.; Kilbourn, M. R.; Pillai, M. R. A.; Rajan, M. G. R.; Wagner, H. N.; Zaknun, J. J.

    2010-01-01

    Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 (F-18) tracers that can be used for PET studies

  2. The added value of Good Manufacturing Practices (GMP) in the production of radiopharmaceuticals

    NARCIS (Netherlands)

    Gerrits, Edwin; Woerdenbag, Herman; Luurtsema, Geert; de Hooge, Marjolijn; Boersma, Hendrikus

    2017-01-01

    Manufacturers of medicinal products including radiopharmaceuticals have to follow regulations from their governmental organizations as well as professional societies to ensure built-in quality combined with patient safety issues. This chapter is a concise review of Good Manufacturing Practices (GMP)

  3. Tracers to monitor the response to chemotherapy: in vitro screening of four radiopharmaceuticals.

    NARCIS (Netherlands)

    Geus-Oei, L.F. de; Eerd-Vismale, J.E.M. van; Molthoff, C.F.M.; Corstens, F.H.M.; Oyen, W.J.G.; Boerman, O.C.

    2004-01-01

    OBJECTIVES: It has been postulated that radiopharmaceuticals can be used to predict the therapeutic response to (chemo)therapy, which could lead to individualized treatment regimens. In this study, 18F-deoxyglucose, 99mTc-tetrofosmin, 125I-deoxyuridineribose, and 125I-methyltyrosine were tested for

  4. European regulations for the introduction of novel radiopharmaceuticals in the clinical setting.

    Science.gov (United States)

    Decristoforo, Clemens; Penuelas, Ivan; Patt, Marianne; Todde, Sergio

    2017-06-01

    The development of novel radiopharmaceuticals is very rapid and highly innovative both for diagnostic and therapeutic applications. The translation into the clinic, however, is hampered by the high regulatory demands in Europe. This article describes the main rules, guidelines and guidance documents in the European Union in relation to the pharmaceutical regulatory framework. Until today a great number of radiopharmaceuticals are introduced clinically using specific national pathways outside the clinical trial regulation and examples are provided. In this context, the European Pharmacopoeia with a legal status plays an important role in defining quality standards. For clinical trials the application system and regulatory framework in Europe is currently considerably changing. Whereas the current clinical trial directive requires a lengthy and complicated national application process, the new regulation 536/2014 will introduce a streamlined and unified European application process. This new regulation also takes into account the specific properties of radioactive investigational medicinal products and has introduced exceptions for good manufacturing practices (GMP) and labelling for radiopharmaceuticals. Besides the main regulatory texts, several guidelines have been published, e.g. related to toxicity testing or first in man studies. In relation to radiopharmaceuticals professional organization, in particular the EANM, have published a number of documents in relation to GMP, documentation and toxicity studies, that support professionals in the application process. All these documents are summarized and discussed.

  5. Implementation of a metrology programme to provide traceability for radionuclides activity measurements in the CNEN Radiopharmaceuticals Producers Centers

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Erica A.L. de; Braghirolli, Ana M.S.; Tauhata, Luiz; Gomes, Regio S.; Silva, Carlos J., E-mail: erica@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Delgado, Jose U.; Oliveira, Antonio E.; Iwahara, Akira, E-mail: ealima@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    The commercialization and use of radiopharmaceuticals in Brazil are regulated by Agencia Nacional de Vigilancia Sanitaria (ANVISA) which require Good Manufacturing Practices (GMP) certification for Radiopharmaceuticals Producer Centers. Quality Assurance Program should implement the GMP standards to ensure radiopharmaceuticals have requirements quality to proving its efficiency. Several aspects should be controlled within the Quality Assurance Programs, and one of them is the traceability of the Radionuclides Activity Measurement in radiopharmaceuticals doses. The quality assurance of activity measurements is fundamental to maintain both the efficiency of the nuclear medicine procedures and patient and exposed occupationally individuals safety. The radiation doses received by patients, during the nuclear medicine procedures, is estimated according to administered radiopharmaceuticals quantity. Therefore it is very important either the activity measurements performed in radiopharmaceuticals producer centers (RPC) as the measurements performed in nuclear medicine services are traceable to national standards. This paper aims to present an implementation program to provide traceability to radionuclides activity measurements performed in the dose calibrators(well type ionization chambers) used in Radiopharmaceuticals Producer Center placed in different states in Brazil. The proposed program is based on the principles of GM Pand ISO 17025 standards. According to dose calibrator performance, the RPC will be able to provide consistent, safe and effective radioactivity measurement to the nuclear medicine services. (author)

  6. The radiopharmaceuticals labelled with technetium-99m and the radiopharmacy; Les radiopharmaceutiques marques au technetium-99m et la radiopharmacie

    Energy Technology Data Exchange (ETDEWEB)

    Bodenant, V

    1998-10-01

    In less than fifty years, the place of nuclear medicine is become primordial. Among all the radiopharmaceuticals used in nuclear medicine, the technetium-99m is the most used because of its physico-chemical properties and its great availability with the molybdenum-99m - technetium-99m generator. Since 1992, the radiopharmaceuticals, the packages, the generators are included in the pharmaceutic monopole. They are now under the reliability of the radio-pharmacist. This thesis has for object to introduce these different radiopharmaceuticals labelled with technetium-99m and to show the primordial place of the radio-pharmacist in a service of nuclear medicine. (N.C.)

  7. Understanding radioxenon isotopical ratios originating from radiopharmaceutical facilities

    Science.gov (United States)

    Saey, P. R. J.; Ringbom, A.; Bowyer, T. W.; Becker, A.; de Geer, L.-E.; Nikkinen, M.; Payne, R. F.

    2009-04-01

    It was recently shown that radiopharmaceutical facilities (RPF) are major contributors to the general background of 133Xe and other xenon isotopes both in the northern and southern hemisphere. To distinguish a nuclear explosion signal from releases from civil nuclear facilities, not only the activity concentrations but also the ratios of the four different CTBT relevant radioxenon isotopes (131mXe, 133mXe, 133Xe and 135Xe) have to be well understood. First measurements taken recently in and around two of the world's largest RPF's: NTP at Pelindaba, South Africa and IRE at Fleurus, Belgium have been presented. At both sites, also stack samples were taken in close cooperation with the facility operators. The radioxenon in Belgium could be classified in four classes: the normal European background (133Xe activity between 0 - 5 mBq/m3) on one hand and then the samples where all four isotopes were detected with 133mXe/131mXe > 1. In northern South Africa the Pelindaba RPF is in practice the sole source of radioxenon. It generated a background of 133Xe at the measurement site some 230 km to the west of the RPF of 0 - 5 mBq/m3. In the cases where the air from the Pelindaba facility reached the measurement site directly and in a short time period, the 133Xe was higher, also 135Xe was present and in some samples 133mXe as well. The ratios of the activity concentrations of 135Xe/133Xe vs. 133mXe/131mXe (Multiple Isotope Ratio Plot - MIRC) have been analysed. For both facilities, the possible theoretical ratio's for different scenarios were calculated with the information available and compared with the measurements. It was found that there is an excess of 131mXe present in the European samples compared to theoretical calculations. A similar excess has also been seen in samples measured in northern America. In South Africa, neither the environmental samples nor the stack ones contained 131mXe at measurable levels. This can probably be explained by different processes and

  8. A rapid and efficient preparation of [{sup 123}I]radiopharmaceuticals using a small HPLC Rocket[reg] column

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, Andrew [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia)]. E-mail: akx@ansto.gov.au; Papazian, Vahan [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia); Jackson, Timothy [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia); Loc' h, Christian [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia)

    2006-01-01

    A simplified method for the rapid and efficient preparation of [{sup 123}I]radiopharmaceuticals is described. Three radiopharmaceuticals, [{sup 123}I]{beta}-CIT, [{sup 123}I]MIBG and [{sup 123}I]clioquinol, were synthesised and purified as model compounds. The radiotracers were labelled with iodine-123 using electrophilic oxidative conditions and purified by a compact semi-preparative reverse phase column (C-18, 3 {mu}m, 7x53 mm, Alltima Rocket[reg, Alltech] using aqueous-ethanol as HPLC solvents that were directly used for radiopharmaceutical formulation. The radiochemical purity of the radioiodinated tracers as assessed by analytical HPLC was higher than 99% with specific activity higher than 3 GBq/nmol. The total preparation time of a radiotracer ranged from 40 to 60 min and, starting from 3.7 GBq of iodine-123, more than 2.5 GBq of formulated radiopharmaceuticals were available for clinical investigations.

  9. Sensitive determination of specific radioactivity of positron emission tomography radiopharmaceuticals by radio high-performance liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Nakao, Ryuji; Furutsuka, Kenji; Yamaguchi, Masatoshi; Suzuki, Kazutoshi

    2008-10-01

    A sensitive quality control method is often required in positron emission tomography (PET) radiopharmaceutical analysis due to the high specific radioactivity of synthetic products. The applicability of a radio high-performance liquid chromatography (HPLC) method with fluorescence detection was evaluated for a wide variety of PET radiopharmaceuticals. In 29 different radiopharmaceuticals studied, 20 compounds exhibited native fluorescence. These properties enabled sensitive determination of their chemical masses by direct fluorimetric detection after separation by HPLC. For some substances, detection limits were below nanograms per milliliter level, at least 40 times better than current UV absorbance detection. Sufficient reproducibility and linearity were obtained for the analysis of pharmaceutical fluid. Post-column fluorimetric derivatization was also established for the quantitative determination of FDG and ClDG in [(18)F]FDG samples. These methods could be applied successfully to the analysis of PET radiopharmaceuticals with ultra-high specific radioactivity.

  10. Preliminary study fo the interference of proteic compounds of radiopharmaceuticals in the test of lisadode amebocitos de limulus (LAL)

    CERN Document Server

    Aldana, C

    1997-01-01

    In this thesis the objective was evaluate the interference of proteic compounds of the radiopharmaceuticals in the test LAL (lisado of amebocitos de limulus) for this, macroagregates of albumina (MAA) was used with metilendifosfonato (MDP) as control that is the radiopharmaceutical more used in the nuclear medicine centers of the country. Initially preliminary test were carried out to assess if some of two radiopharmaceuticals would cause interference with LAL test, after the test was validated and finally routine tests were made. With the preliminary assays was concluded that proteic compounds did not cause interference (albumina with a concentration of 2 md/dl) with the MAA. However with the MDP cause interference with LAL test. The interference was eliminated with a dilution of 1:8 of the sample. Was concluded that the success of LAL test depends on conditions such as temperature, pH, constant incubation (no minimum variations) and that is a good test for quality control of the radiopharmaceuticals.

  11. Development of a modular system for the synthesis of PET [(11)C]labelled radiopharmaceuticals.

    Science.gov (United States)

    Boschi, Stefano; Lodi, Filippo; Cicoria, Gianfranco; Raul Ledesma, Jorge; Knopp, Roger; Rizzello, Anna; Di Pierro, Donato; Trespidi, Silvia; Marengo, Mario

    2009-10-01

    [((11))C]labelled radiopharmaceuticals as N-[(11)C]methyl-choline ([(11)C]choline), l-(S-methyl-[(11)C])methionine ([(11)C]methionine) and [(11)C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [(11)C]choline, [(11)C]methionine and [(11)C]acetate using components that account for straightforward scaling up and upgrades.

  12. Development of a modular system for the synthesis of PET [{sup 11}C]labelled radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Boschi, Stefano [PET Radiopharmacy, Nuclear Medicine, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna (Italy)], E-mail: stefano.boschi@aosp.bo.it; Lodi, Filippo [PET Radiopharmacy, Nuclear Medicine, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna (Italy); Cicoria, Gianfranco [Medical Physics, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi (Italy); Raul Ledesma, Jorge [Fundacion Escuela de Medicina Nuclear, Mendoza (Argentina); Knopp, Roger [Eckert Ziegler-Eurotope, Berlin (Germany); Rizzello, Anna; Di Pierro, Donato; Trespidi, Silvia [PET Radiopharmacy, Nuclear Medicine, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna (Italy); Marengo, Mario [Medical Physics, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi (Italy)

    2009-10-15

    [{sup 11}C]labelled radiopharmaceuticals as N-[{sup 11}C]methyl-choline ([{sup 11}C]choline), L-(S-methyl-[{sup 11}C])methionine ([{sup 11}C]methionine) and [{sup 11}C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [{sup 11}C]choline, [{sup 11}C]methionine and [{sup 11}C]acetate using components that account for straightforward scaling up and upgrades.

  13. Novel diagnostic and therapeutic radionuclides for the development of innovative radiopharmaceuticals

    CERN Multimedia

    We propose the exploration of novel radionuclides with diagnostic or therapeutic properties from ISOLDE. Access to such unique isotopes will enable the fundamental research in radiopharmaceutical science towards superior treatment, e.g. in nuclear oncology. The systematic investigation of the biological response to the different characteristics of the decay radiation will be performed for a better understanding of therapeutic effects. The development of alternative diagnostic tools will be applied for the management and optimization of radionuclide therapy.

  14. The foundations of the development of technologies of the synthesis of radiopharmaceuticals

    Science.gov (United States)

    Larkina, M.; Podrezova, E.; Bragina, O.; Stasyuk, E.; Yusubov, M.; Chernov, V.; Zelchan, R.; Skuridin, V.; Belousov, M.; Deyev, S.

    2017-09-01

    The selection of precursors (for example chelating agents) and development of a technique of chemical modification of the target molecules retaining its ability to bind to specific receptors are very important in the synthesis of radiopharmaceuticals. As some important precursors for target radiopharmaceuticals omega-iodo-aliphatic carboxylic acids and their esters can be used. We have developed an environmentally safe process for producing omega-iodo-aliphatic carboxylic acids and their esters of the available, inexpensive and low toxic aliphatic cyclic ketones. We proposed a new method for the synthesis of the chelating agents omega-thia- or (bis(2-hydroxyethyl)amino)- aliphatic carboxylic acids (chelate 1 and chelate 2), which was caused by the existing disadvantages in the existing methods. Thus, based on our method the precursors (chelates) with yield of over 70-90% on the final stage were synthesized, and then the high effectiveness in producing target radiopharmaceuticals using different biomolecules was showed. 99mTc-chelates complexes were prepared with radiochemical purity >91% and found to be stable at room temperature for six hours.

  15. Harvard-MIT research program in short-lived radiopharmaceuticals. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J. [Massachusetts Inst. of Tech., Cambridge, MA (United States). Office of Sponsored Programs

    1995-02-01

    The Harvard-MIT Research Program in Short-lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working in radiopharmaceutical chemistry at Harvard Medical School, the Massachusetts Institute of Technology, and the Massachusetts General Hospital. To this was added a group at The Childrens Hospital. From these collaborations and building upon the special strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, radiolabeled compounds. The original thrust of this proposal included: (a) examination of the coordination chemistry of technetium as a basis for rational radiopharmaceutical design, (b) development of an ultrashort-lived radionuclide generator for the diagnosis of congenital heart disease in newborns, (c) synthesis of receptor-site-directed halopharmaceuticals, (d) improved facile labeling of complex molecules with positron-emitting radionuclides. The authors` 1986 proposal was oriented toward organs and disease, emphasizing radiolabeled agents that delineate specific functions and the distribution of receptors in brain, heart, and tumors. In 1989, they further refined their purposes and focused on two major aims: (a) synthesis and utilization of neutral technetium and rhenium complexes of high specific activity, and (b) development of new approaches to the radiolabeling of proteins, peptides, immunoglobulins, and their fragments. In 1992, the authors amended this proposal to concentrate their efforts on biologically active peptides and proteins for targeted radiodiagnosis and therapy.

  16. Synthetic techniques of radiopharmaceuticals production labeled with C-11 for PET in cardiology

    Science.gov (United States)

    Dyubkov, V. S.; Ekaeva, I. V.; Katunina, T. A.; Rumyantsev, A. S.; Silchenkov, A. V.; Tuflina, T. V.

    2017-01-01

    Positron emission tomography (PET) and PET-Computerised Tomography (CT) are unique, non-invasive diagnostic techniques, in which the local, temporal and quantitative distributions of radioactive labelled substances are measured to investigate physiological processes. It is well known that PET centre of Bakulev Scientific Centre for Cardiovascular Surgery is the oldest one in Moscow. During more than fifteen years a large number of patients have received PET scans. Due to main stream of Scientific Centre, emphasis is placed on examining the heart functioning. For the diagnosis innervation of the heart muscle a number of radiopharmaceuticals are used, including PET radiopharmaceuticals such as 11C-CGP 12177, 11C-meta-hydroxyephedrine as well as its synthetic analogues labelled with other PET radionuclides (18F, 68Ga). 11C-meta-hydroxyephedrine is one of the most perspective radiopharmaceutical for an investigation of cardiac receptors function due to required materials availability for a radio synthesis in Russia. The main advantage of proposed 11C-meta-hydroxyephedrine synthesis technique is the use of a catalyst which allows one decrease reaction time from 5 minutes to 30 seconds. Obtained results allow one decrease reaction time of methylation and increase radiochemical and technological yields.

  17. Overview of internal dose evaluation in the radiopharmaceutical production plant at IPEN

    Energy Technology Data Exchange (ETDEWEB)

    Todo, Alberto S.; Gerulis, Eduardo; Cardoso, Joaquim C.S.; Rodrigues Junior, Orlando, E-mail: astodo@ipen.br, E-mail: rodrijr@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    The internal dosimetry program at the Instituto de Pesquisas Energeticas e Nucleares, IPEN, is accomplished in two steps: the activity measurements are performed at the In Vivo Monitoring Laboratory and subsequently the data analysis and the dose evaluation are carried out by the Dose Calculation Group according to the ICRP models. The objective of this study is to take the whole body and thyroid monitoring results recorded from 2005 to 2015 to see whether the internal contamination control procedure for workers were suitable even with the increase in the radiopharmaceutical production. The study were based in a research called “Search of Variables” for the operations carried out in the restricted areas of radiopharmaceutical production plant, taking into account the dose distribution data for all the tasks recorded by the radioprotection service. This methodology aims to identify and determine the principal variables that impact on the worker's dose. The results were presented for the following variables: individual occupationally exposed, operation variable, area/cell, type of task of operation, which depend on the variable dose. In spite of growth rate in the production of radiopharmaceutical, this study has shown that the improvements in the plant have contributed to the dose reduction of the workers. (author)

  18. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1977-October 31, 1980

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1980-06-01

    Although the germanium-68 ..-->.. gallium-68 generator is probably the only source of positron-emitting radionuclides that could enable the widespread application of positron tomography, the commercially available /sup 68/Ga//sup 68/Ge generator system suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, which forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than /sup 68/Ga-EDTA, it is first necessary to break the stable EDTA complex and remove all traces of EDTA. This procedure adds several steps and a significant amount of time to procedures for preparing /sup 68/Ga-radiopharmaceuticals. We have developed a new generator using a solvent extraction system which will produce /sup 68/Ga-oxine (8-hydroxyquinoline), a weak chelate. Using this agent we have synthesized several /sup 68/Ga-radiopharmaceuticals and tested them in vitro and in vivo. We have also carried out some preliminary studies to compare generator systems which produce /sup 68/Ga in an ionic form. Attempts have been made using polarographic and chromatographic techniques, and in vivo distribution data to investigate the stability of radiogallium complexes with a series of potentially lipophilic complexing agents.

  19. Bone-seeking radiopharmaceuticals as targeted agents of osteosarcoma: samarium-153-EDTMP and radium-223.

    Science.gov (United States)

    Anderson, Peter M; Subbiah, Vivek; Rohren, Eric

    2014-01-01

    Osteosarcoma is a cancer characterized by formation of bone by malignant cells. Routine bone scan imaging with Tc-99m-MDP is done at diagnosis to evaluate primary tumor uptake and check for bone metastases. At time of relapse the Tc-99m-MDP bone scan also provides a specific means to assess formation of bone by malignant osteosarcoma cells and the potential for bone-seeking radiopharmaceuticals to deliver radioactivity directly into osteoblastic osteosarcoma lesions. This chapter will review and compare a bone-seeking radiopharmaceutical that emits beta-particles, samarium-153-EDTMP, with an alpha-particle emitter, radium-223. The charged alpha particles from radium-223 have far more mass and energy than beta particles (electrons) from Sm-153-EDTMP. Because radium-223 has less marrow toxicity and more radiobiological effectiveness, especially if inside the bone forming cancer cell than samarium-153-EDTMP, radium-223 may have greater potential to become widely used against osteosarcoma as a targeted therapy. Radium-223 also has more potential to be used with chemotherapy against osteosarcoma and bone metastases. Because osteosarcoma makes bone and radium-223 acts like calcium, this radiopharmaceutical could possibly become a new targeted means to achieve safe and effective reduction of tumor burden as well as facilitate better surgery and/or radiotherapy for difficult to resect large, or metastatic tumors.

  20. Radiochemical quality control of 99mTc-labeled radiopharmaceuticals. Some daily practice guideliens.

    Science.gov (United States)

    Pauwels, E K; Feitsma, R I

    1977-06-30

    Recognizing the fact that each nuclear medicine facility should be able to perform simple radiochemical quality tests on currently used radiopharmaceuticals, this study was undertaken to evaluate a number of radiochromatographic methods. No single ideal method exists to assess the radiochemical composition of 99mTc-labeled antimony sulphur colloid, sulphur colloid, iron ascorbate, citrate, human serum albumin, EHDP, macroaggregates, and microspheres. It is advisable to include thin layer chromatography with both NaCl and methylethylethylketone for the determination of free pertechnetate in each day's program. More detailed radiochemical analysis can be performed by combining these methods with paper chromatography, paper electrophoresis, and gel filtration. It seems reasonable to regard a constant radiochromatographic pattern as a measure for constant radiochemical quality. The four chromatographic tests lead to consistent results regarding the percentage of free pertechnetate in the radiopharmaceutical preparations. Quantitative analysis shows that the radiochemical purity for each radiopharmaceutical is unique for the chromatographic method used and needs to be defined when stated.

  1. The fourteenth report on survey of adverse reaction to radiopharmaceuticals; The 17th survey in 1991

    Energy Technology Data Exchange (ETDEWEB)

    1993-05-01

    This report deals with adverse reactions to radiopharmaceuticals occurring during the period from April 1, 1991 through March 31, 1992. Questionnaires were sent to 1,150 facilities, and 906 (78.8%) responded. Twenty one cases of adverse reactions and 7 cases of drug defects were reported from a total of 19 facilities (2.1%), giving an annual incidence of 2.0 and 0.7 cases, respectively, for 100,000 administered cases. The ratio of the occurrence in the 17th survey to that in the 16th survey was 1.18 for adverse reactions and 0.39 for drug defects. The occurrence of drug defects in this survey was lowest compared with that in the previous five surveys. According to radiopharmaceuticals, the incidence of adverse reactions was as follows: I-131-6[beta]-iodomethyl-19-norcholesterol>I-123 orthoiodohippurate>I-131 orthoiodohippurate>Tc-99m DMSA>Tc-99m DTPA>Tc-99m MAA>Ga-67 citrate>Tc-99m MDP>Tc-99m HMDP. Adverse reactions included reactions to the vagus nerves (n=9), allergic reactions (n=3), and others (n=9). Radiopharmaceuticals reported as drug defects were as follows: Tc-99m pertechnetate, Tc-99m MDP, Tc-99m HMDP, Tc-99m phytate, and Tl-201 chloride. (N.K.).

  2. Adverse reactions to radiopharmaceuticals in France: analysis of the national pharmacovigilance database.

    Science.gov (United States)

    Laroche, Marie-Laure; Quelven, Isabelle; Mazère, Joachim; Merle, Louis

    2015-01-01

    Radiopharmaceuticals are regarded as safe by the nuclear medicine community, but up to now, no survey has been conducted with from the perspective of pharmacovigilance. To describe the adverse reactions to radiopharmaceuticals (ARRPs) reported to the French Pharmacovigilance Database (FPVD). We selected and described all reports encompassing at least one radiopharmaceutical in the FPVD. The annual incidence of reported ARRPs used in diagnosis was also estimated. From 1989 to 2013, 304 reports of ARRPs were identified (43.0% serious, 12 deaths) in 54.6% women and 45.4% men; the median age was 58 years. Five therapeutic radiopharmaceuticals ((131)I-sodium iodide, (131)I-lipiodol, (89)Sr-chloride, (153)Sm-lexidronam, and (90)Y-ibritumomab-tiuxetan) were involved in 48 reports (97 adverse reactions: 86.6% serious, 9 deaths). Pulmonary disorders represented 44.3% of ARRPs used for therapy, mainly related to (131)I-lipiodol. There were 34 diagnostic radiopharmaceuticals involved in 256 reports (451 adverse reactions: 38.1% serious, 3 deaths); 8 diagnostic products ((99m)Tc-oxidronate, (18)F-fluorodeoxyglucose, (99m)Tc-tin pyrophosphate, (99m)Tc-tetrofosmin, (99m)Tc-dimercaptosuccinic acid, (201)Tl-chloride, (99m)Tc-sestamibi, and (111)In-pentetate) accounted for two-thirds of ARRPs. The most frequent adverse reactions were skin (34.4%), general (18.2%), nervous (9.0%), and gastrointestinal disorders (7.0%). There were 25 cases of altered images and 10 medication errors. The annual incidence of reported adverse reactions ranged from 1.2 × 10(-5) to 3.4 × 10(-5) diagnostic administrations. Reported ARRPs occurred rarely and were more serious in the therapeutic than in the diagnostic field. The notification of ARRPs was able to provide new guidance for safe use, as was the case for (131)I-lipiodol. Therefore, it is important to report ARRPs to a pharmacovigilance system. © The Author(s) 2014.

  3. SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, F [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil); Silva, D da [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Rodrigues, L [Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil)

    2015-06-15

    Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: {sup 18}F (109,7 min, 249,8 keV), {sup 89}Zr (78,4 hs, 395,5 keV), {sup 11}C (20,4 min, 385,7 keV) and {sup 68}Ga (67,8 min, 836 keV). {sup 68}Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ({sup 18}F-FDG), lipogenesis ({sup 11}C-Choline and {sup 11}C-Acetate), amino acid transport (Anti-{sup 18}F-FACBC), bone matrix ({sup 18}F-NaF), prostatespecific membrane antigen ({sup 68}Ga-PSMA and {sup 89}Zr-J591), CXCR receptors ({sup 89}Ga-Pentixafor), adrenal receptors ({sup 18}F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-{sup 18}FFACBC (liver) and {sup 18}F-FBDC (stomach wall) are the exception. Higher effective dose was seen {sup 18}F-NaF (27 μSv/MBq) while the lowest was {sup 11}CAcetate (3,5 μSv/MBq). Conclusion: Even though {sup 18}F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when {sup 18}F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider {sup 11}C or {sup 18}F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for {sup 18}F labeling. Anti-{sup 18}F-FACBC, {sup 68}Ga-PSMA and {sup

  4. Introduction to the use of FRAM on the effectiveness assessment of a radiopharmaceutical dispatches process

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Ana G.A.A., E-mail: agaap@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    This article aims to make an introduction to the use of Functional Resonance Analysis Method (FRAM) on the effectiveness assessment of a specific radiopharmaceutical dispatching process. The main purpose was to provide a didactic view of the method application to further in-depth analysis. The investigation also provided a relevant body of knowledge of radiopharmaceuticals dispatches processes. This work uses the term 'effectiveness assessment' instead of 'risk assessment' due to the broader meaning the former provide. The radiopharmaceutical dispatching process is the final task of a dynamic system designed to attend several medical facilities. It is comprised by functions involving mostly human activities, such as checking and packaging the product and measuring the radiopharmaceutical nuclear activity. Although the dispatch process has well-known steps for its completion, the human factor is the fundamental mechanism of work and control, being susceptible of irregular and instable performance. As a socio-technical system, the risk assessment provided by FRAM may be of importance for safety and quality improvements, even more if considered the nuclear nature of the product, which makes risk assessment critical and mandatory. A system is safe if it is resistant and resilient to perturbations. Identification and assessment of possible risks is, therefore, an essential prerequisite for system safety. Although this seems obvious, most risk assessments are conducted under relative ignorance of the full behavior of the system. Such condition has lead to an approach to assess the risks of intractable systems (i.e., systems that are incompletely described or under specified), namely Resilience Engineering. Into this area, the Functional Resonance Analysis Method has been developed in order to provide concepts, terminology and a set of methods capable of dealing with such systems. The study was conducted following the Functional Resonance Analysis

  5. Efficiancy of hydrogen peroxide for cleaning production areas and equipments in the radiopharmaceutical production

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Tatyana S.; Batista, Vanessa; Gomes, Antonio; Matsuda, Margareth; Fukumori, Neuza; Araujo, Elaine B. de, E-mail: tsbaptista@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    A great challenge in the radiopharmaceuticals production is to fulfill the Good Manufacturing Practices (GMPs), involving the validation of process and of all supporting activities such as cleaning and sanitization. The increasingly strict requirements for quality assurance system, with several norms and normative resolutions has led to a constant concern with programs and cleaning validation in pharmaceutical production. The main goal of GMP is to reduce risks inherent to pharmaceutical production, that is to reduce product contamination with microorganisms and cross-contamination. The basic requirements to prevent contamination is the development and implementation of efficient cleaning programs. In the case of clean rooms for the production of injectable radiopharmaceuticals, the requirement for cleaning programs is evidently higher due to the characteristics of these areas with hot cells for radioactive materials, where sterile radiopharmaceuticals are manipulated and distributed before administration to patients just after minutes or hours of its preparation. In the Radiopharmacy Department at IPEN it was established a cleaning program for clean rooms and hot cells using a hydrogen peroxide solution (20% proxitane alfa). The objective of this work was to assess effectiveness of this cleaning agent in reducing and/or eliminating microbial load in the clean rooms and equipment to acceptable levels in accordance with the current legislation. The analysis was conducted using results of the environmental monitoring program with and settling contact plates in clean rooms after the cleaning procedures. Furthermore, it was possible to evaluate the action of the sanitizing agent on the microbial population on the surface of equipment and clean rooms. It was also evaluated the best way to accomplish the cleaning program considering the dosimetric factor in each production process, as the main concern of pharmaceutical companies is the microbiological contamination, in

  6. Nuclear cardiology, Part II: Scintigraphic evaluation of cardiac function.

    Science.gov (United States)

    Hambÿe, A S; Everaert, H; Maes, A; Mesotten, L; Vandevivere, J; Mortelmans, L; Franken, P R

    1998-06-01

    Different methods are currently available to assess cardiac function, especially left ventricular ejection fraction, using either planar or tomographic imaging, first-pass or equilibrium techniques, and blood-pool or myocardial perfusion agents. This is the second article of a four-part series on nuclear cardiology. In this article the authors review the most widely used radiopharmaceuticals and methodologies.

  7. Synthesis and Characterization of a Tetramethyl Furanone Functionalized Diiminedioxime, A Potential Ligand for Cu Radiopharmaceuticals, and its Copper(II) and Nickel(II) Complexes.

    Science.gov (United States)

    Kiani, Salma; Staples, Richard J; Treves, S Ted; Packard, Alan B

    2009-03-12

    As part of our on-going effort to develop (64)Cu-based radiopharmaceuticals for PET (positron emission tomography) imaging of multidrug resistance in cancer, we prepared a tetramethylfuranone-functionalized diiminedioxime ligand, TMFPreH (TMFPreH = 4-[3-(4-Hydroxyimino-2,2,5,5-dimethyl-dihydro-furan-3-ylideneamino)-propylimino]-2,2,5,5-tetramethyl-dihydro-furan-3-one oxime) and its Cu(II) and Ni(II) complexes. When the copper(II) complex was prepared from Cu(ClO(4))(2) in ethanol, it was isolated as a Cu(II)-bridged dimer, but when it was prepared from Cu(OAc)(2) and heated in acetone, an unusual example of an acetone adduct of the ligand is formed by reduction of one of the imine double bonds by the solvent. The Ni(II) complex is square pyramidal with the perchlorate counterion at the apex.

  8. Drug interaction with radiopharmaceuticals: effect on the labeling of red blood cells with technetium-99m and on the bioavailability of radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Maria Luisa Gomes

    2002-09-01

    Full Text Available The evidence that natural and synthetic drugs can affect radiolabeling or bioavailability of radiopharmaceuticals in setting of nuclear medicine clinic is already known. However, this drug interaction with radiopharmaceuticals (DIR is not completely understood. Several authors have described the effect of drugs on the labeling of blood elements with technetium-99m (99mTc and on the biodistribution of radiopharmaceuticals. When the DIR is known, if desirable or undesirable, the natural consequence is a correct diagnosis. However, when it is unknown, it is undesirable and the consequences are the possibility of misdiagnosis and/or the repetition of the examination with an increase of radiation dose to the patient. The possible explanation to the appearance of DIR are (a radiopharmaceutical modification, (b alteration of the labeling efficiency of the radiopharmaceutical, (c modification of the target, (d modification of no target and/or the (e alteration of the binding of the radiopharmaceutical on the blood proteins. The effect of drugs on the labeling of blood elements with 99mTc might be explained by (i a direct inhibition (chelating action of the stannous and pertechnetate ions, (ii damage induced in the plasma membrane, (iii competition of the cited ions for the same binding sites, (iv possible generation of reactive oxygen species that could oxidize the stannous ion and/or (v direct oxidation of the stannous ion. In conclusion, the development of biological models to study the DIR is highly relevant.A evidência de que drogas naturais ou sintéticas podem afetar a radiomarcação ou a biodisponibilidade de radiofármacos nos procedimentos de medicina nuclear já é bem conhecida. Entretanto, essa interação de droga com radiofármacos (IDR não está completamente compreendida. Vários autores têm descrito o efeito de drogas na marcação de elementos sanguíneos com tecnécio-99m (99mTce na biodistribuição de radiofármacos. Quando a

  9. Binding studies of the antitumoral radiopharmaceutical 125I-Crotoxin to Ehrlich ascites tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina B.; Santos, Raquel G. dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Dias, Consuelo L. Fortes [Fundacao Ezequiel Dias (FUNED), Belo Horizonte, MG (Brazil)], e-mail: consuelo@pq.cnpq.br; Cassali, Geovanni D. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada], e-mail: cassalig@icb.ufmg.br

    2009-07-01

    The development of tools for functional diagnostic imaging is mainly based on radiopharmaceuticals that specifically target membrane receptors. Crotoxin (Crtx), a polypeptide isolated from Crotalus durissus terrificus venom, has been shown to have an antitumoral activity and is a promising bioactive tracer for tumor detection. More specific radiopharmaceuticals are being studied to complement the techniques applied in the conventional medicine against breast cancer, the most frequent cause of death from malignant disease in women. Crtx's effect has been shown to be related with the overexpression of epidermal growth factor receptor (EGFR), present in high levels in 30 to 60% of breast tumor cells. Our objective was to evaluate Crtx as a tracer for cancer diagnosis, investigating its properties as an EGFR-targeting agent. Ehrlich ascites tumor cells (EAT cells) were used due to its origin and similar characteristics to breast tumor cells, specially the presence of EGFR. Crtx was labeled with 125I and binding experiments were performed. To evaluate the specific binding in vitro of Crtx, competition binding assay was carried out in the presence of increasing concentrations of non-labelled crotoxin and epidermal growth factor (EGF). Specific binding of 125I-Crtx to EAT cells was determined and the binding was considered saturable, with approximately 70% of specificity, high affinity (Kd = 19.7 nM) and IC50 = 1.6 x 10-11 M. Our results indicate that Crtx's interaction with EAT cells is partially related with EGFR and increases the biotechnological potential of Crtx as a template for radiopharmaceutical design for cancer diagnosis. (author)

  10. Eye lens dosimetry in workers of a PET radiopharmaceutical production facility

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes, M. C.; Lacerda, M. A. S.; Da Silva, T. A. [Development Center of Nuclear Technology, Posgraduate Course in Science and Technology of Radiations, Minerals and Materials, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil); Meireles, L. S.; Teles, L. L. D., E-mail: margaretecristinag@gmail.com [Development Center of Nuclear Technology / CNEN, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil)

    2015-10-15

    Full text: A new regulatory statement was issued concerning the eye lens radiation protection of persons in some planned exposures. A debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to establish the dosimetry procedure with the Eye-D{sup TM} holder with a MCP-N LiF:Mg,Cu,P thermoluminescent chip detector for measuring the personal dose equivalent Hp(3) in workers of the Development Center of Nuclear Technology (DCNT) Positron-Electron Tomography (PET) Radiopharmaceuticals Production Facility (RPF). The eye lens dosimeter was calibrated and its energy response was studied in terms Hp(3) on a ISO standard slab phantom and on a recent suggested cylindrical phantom. Irradiations were carried out at the DCNT Dosimeter Calibration Laboratory in ISO reference radiations of {sup 137}Cs gamma, narrow spectrum series X-ray beams, {sup 90}Sr/{sup 90}Y and {sup 85}Kr beta rays. Fifteen workers of the RPF/DCNT were monitored during radiopharmaceutical production activities (e.g. cyclotron operation, quality control tests, radiopharmaceutical production and radioprotection). Considering the predominant exposure to 511 keV photons, the energy dependence of the dosimeter of 30% in energies down to 33 keV should not be a concern. Calibration coefficient of the dosimeter in {sup 137}Cs beam showed that the use of the slab phantom will underestimate the Hp(3) in 8.8% related to the cylindrical phantom. The absorbed dose due to beta radiation exposure seems to be unfeasible to be assessed with the chosen dosimeter. Results showed that the workers responsible for quality control tests received the highest doses and that there is room for optimization. (Author)

  11. USCEA/NIST measurement assurance programs for the radiopharmaceutical and nuclear power industries

    Energy Technology Data Exchange (ETDEWEB)

    Golas, D.B. [Council for Energy Awareness, Washington, DC (United States)

    1993-12-31

    In cooperation with the U.S. Council for Energy Awareness (USCEA), the National Institute of Standards and Technology (NIST) supervises and administers two measurement assurance programs for radioactivity measurement traceability. One, in existence since the mid 1970s, provides traceability to suppliers of radiochemicals and radiopharmaceuticals, dose calibrators, and nuclear pharmacy services. The second program, begun in 1987, provides traceability to the nuclear power industry for utilities, source suppliers, and service laboratories. Each program is described, and the results of measurements of samples of known, but undisclosed activity, prepared at NIST and measured by the participants are presented.

  12. Calculating patient-specific doses in X-ray diagnostics and from radiopharmaceuticals

    Science.gov (United States)

    Lampinen, Juha Sakari

    2000-06-01

    The risk associated with exposure to ionising radiation is dependent on the characteristics of the exposed individual. The size and structure of the individual influences the absorbed dose distribution in the organs. Traditional methods used to calculate the patient organ doses are based on standardised calculation phantoms, which neglect the variance of the patient size or even sex. Methods for patient specific dosimetry in the fields of X-ray diagnostics and diagnostic and therapeutic use of radiopharmaceuticals were proposed in this thesis. A computer program, ODS-60, for calculating organ doses from diagnostic X-ray exposures was presented. The calculation is done in a patient specific phantom with depth dose and profile algorithms fitted to Monte Carlo simulation data from a previous study. Improvements to the version reported earlier were introduced, e.g. bone attenuation was implemented. The applicability of the program to determine patient doses from complex X-ray examinations (barium enema examination) was studied. The conversion equations derived for female and male patients as a function of patient weight gave the smallest deviation from the actual patient doses when compared to previous studies. Another computer program, Intdose, was presented for calculation of the dose distribution from radiopharmaceuticals. The calculation is based on convolution of an isotope specific point dose kernel with activity distribution, obtained from single photon emission computed tomography (SPECT) images. Anatomical information is taken from magnetic resonance (MR) or computed tomography (CT) images. According to a phantom study, Intdose agreed within 3% with measurements. For volunteers administered diagnostic radiopharmaceuticals, the results given by Intdose were found to agree with traditional methods in cases of medium sized patients. For patients undergoing systemic radiation therapy, the results by Intdose differed from measurements due to dynamic biodistribution

  13. Reliability of eye lens dosimetry in workers of a positron emission tomography radiopharmaceutical production facility.

    Science.gov (United States)

    da Silva, Teógenes A; Guimarães, Margarete C; Meireles, Leonardo S; Teles, Luciana L D; Lacerda, Marco Aurélio S

    2016-11-01

    A new regulatory statement was issued concerning the eye lens radiation protection of persons in planned exposures. A debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to establish the individual monitoring procedure with the EYE-D™ holder and a MCP-N LiF:Mg,Cu,P thermoluminescent chip detector for measuring the personal dose equivalent Hp(3) in workers of a Positron Emission Tomography Radiopharmaceutical Production Facility. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Development of Holmium 166-chitosan complex as a radiopharmaceutical agent for liver cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jei Man; Nam, Soon Chul; Park, Sun Joo; Moon, Eun Yi; Lee, Won Yong; Shin, Dong Hyuk; Cho, Eun Hee [Korea Atomic Energy Research Instisute, Taejon (Korea, Republic of)

    1997-09-01

    Effective therapeutic methods for cancer disease should be developed because the frequency of cancer disease is being increased rapidly. But there is no effective therapeutic method for treating these disease until now. The purpose of this research is to gain the clinical approval of Holmium{sup 166}-Chitosan complex as a radiopharmaceutical agent for liver cancer. We finished the preclinical test of Holmium{sup 166}-Chitosan complex and got the approval for clinical trial of this agent. 12 refs., 11 tabs., 9 figs. (author)

  15. Experimental Study of a Radiopharmaceutical Agent Based on Modified Fatty Acid Labeled with Technetium-99m.

    Science.gov (United States)

    Sazonova, S I; Il'yushenkova, Yu N; Lishmanov, Yu B; Tsibul'nikov, S V; Skuridin, V S; Nesterov, E A; Varlamova, N V; Il'ina, E A; Filimonov, V D; Belyanin, M V; Stepanova, E V; Minin, S M

    2017-04-01

    Using rat model of coronary occlusion, we studied pharmacokinetics and the efficiency of a new radiopharmaceutical agent (99m)Tc-PDA-DTPA intended for diagnostics of changes in myocardial metabolism and its analogue (123)I-PMPDA. (99m)Tc-PDA-DTPA was eliminated mostly by the kidneys and maximal concentration in the heart was attained within 60 min after intravenous injection; no accumulation in the area of myocardial infarction was observed. The studied substance was inferior to its analogue 123I-PMPDA by the quality of scintigraphic visualization of the heart.

  16. ACR-ASTRO practice guideline for the performance of therapy with unsealed radiopharmaceutical sources.

    Science.gov (United States)

    Henkin, Robert E; Del Rowe, John D; Grigsby, Perry W; Hartford, Alan C; Jadvar, Hossein; Macklis, Roger M; Parker, J Anthony; Wong, Jeffrey Y C; Rosenthal, Seth A

    2011-08-01

    This guideline is intended to guide appropriately trained and licensed physicians performing therapy with unsealed radiopharmaceutical sources. Adherence to this guideline should help to maximize the efficacious use of these procedures, maintain safe conditions, and ensure compliance with applicable regulations. The topics dealt with in this guideline include indications for the use of iodine-131, both for the treatment of hyperthyroidism and thyroid carcinoma. In addition, indications for other less common procedures include those for the use of phosphorous-32 in its liquid and colloidal forms, strontium-89, samarium-153, and the use of Y-90 antibodies.

  17. A generator-produced gallium-68 radiopharmaceutical for PET imaging of myocardial perfusion.

    Directory of Open Access Journals (Sweden)

    Vijay Sharma

    Full Text Available Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI. However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel 68Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI.

  18. Proliferation dangers associated with nuclear medicine: getting weapons-grade uranium out of radiopharmaceutical production.

    Science.gov (United States)

    Williams, Bill; Ruff, Tilman A

    2007-01-01

    Abolishing the threat of nuclear war requires the outlawing of nuclear weapons and dismantling current nuclear weapon stockpiles, but also depends on eliminating access to fissile material (nuclear weapon fuel). The near-universal use of weapons-grade, highly enriched uranium (HEU) to produce radiopharmaceuticals is a significant proliferation hazard. Health professionals have a strategic opportunity and obligation to progress the elimination of medically-related commerce in HEU, closing one of the most vulnerable pathways to the much-feared 'terrorist bomb'.

  19. Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

    Energy Technology Data Exchange (ETDEWEB)

    Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M. [Austin and Repatriation Medical Centre, Melbourne, VIC (Australia). Centre for Positron Emission Tomography

    1997-10-01

    Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient`s body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t,{sub 1/2}=2min), nitrogen-13 (t{sub 1/2}= 10 min), carbon-11 (t{sub 1/2}=20 min) and fluorine-18 (t{sub 1/2}= 110 min). These radiopharmaceuticals include [{sup 15}O]oxygen, [{sup 15}O]carbon monoxide, [{sup 15}O]carbon dioxide, [{sup 15}O]water, [{sup 13}N]ammonia, [{sup 11}C]flumazenil, [{sup 11}C]SCH23390, [{sup 18}F]fluoromisonidazole and [{sup 18}F]fluoro-deoxy-glucose ([{sup 18}F]FDG). In addition, since the half life of [{sup 18}F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [{sup 18}F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [{sup 18}F]thymidine analog to measure cell proliferation and a [{sup 11}C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors) 23 refs., 2 tabs.

  20. Post-target produced [{sup 18}F]F{sub 2} in the production of PET radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Forsback, Sarita; Solin, Olof [Turku PET Centre, Turku (Finland). Radiopharmaceutical Chemistry Lab. and Accelerator Lab.

    2015-06-01

    Electrophilic radiofluorination was successfully carried out in the early years of PET radiochemistry due to its ease and fast reaction speed. However, at the present, the use of electrophilic methods is limited due to low specific activity (SA). Post-target produced [{sup 18}F]F{sub 2} has significantly higher SA compared to other electrophilic approaches, and it has been used in the production of clinical PET radiopharmaceuticals at the Turku PET Centre for years. Here, we summarize the synthesis and use of these radiopharmaceuticals, namely [{sup 18}F]FDOPA, [{sup 18}F] CFT, [{sup 18}F]EF5 and [{sup 18}F]FBPA.

  1. Measurement and control of the air contamination generated in a medical cyclotron facility for PET radiopharmaceuticals.

    Science.gov (United States)

    Calandrino, R; del Vecchio, A; Todde, S; Fazio, F

    2007-05-01

    The aim of this paper is to report the data concerning the contamination of the exhausted air from the hot cells dedicated to the large-scale synthesis of positron emission tomography (PET) radiopharmaceuticals. Two cyclotrons are currently operating in Ospedale San Raffaele for the routine production of C and F. They are linked with four radiochemistry laboratories by means of shielded radioisotope delivery lines. The above labs are dedicated both to the large scale preparation and to the research and development of PET radiopharmaceuticals. The department hosts four CT-PET scanners, which operate with a mean patient workload of 40 per day. Radiosyntheses are performed using automated modules located in 10 hot cells. The air outlets are monitored online by a 2-inch NaI(Tl) counter in a Marinelli geometry counting volume. Contamination values up to 10(5) Bq L(-1) have been measured at the hot cell exit point during the synthesis. The corresponding concentrations at the point of release in atmosphere are largely above the threshold of 1.29 Bq L(-1), defined by national regulations as the limit for free environmental release. A shielded gas storage system controlled by a dedicated, customized software program has thus been installed to prevent the potentially hazardous release of gaseous radioactive contaminants. The system has allowed us to maintain the effective dose to neighboring population groups below the limit of 10 muSv y(-1).

  2. Direct Technetium radiopharmaceuticals production using a 30MeV Cyclotron

    Science.gov (United States)

    Jalilian, AR.; Targholizadeh, H.; Raisali, GR.; Zandi, H.; Kamali Dehgan, M.

    2011-01-01

    Background and the purpose of the study Technetium-99m is the major radionuclide used in the world and mainly is provided by fission product. However extensive research has been conducted on the use of accelerators for production of 99mTc. This investigation reports the production of 99mTc radioisotope using cyclotrons and the preparation, quality control and biodistribution studies of four major Tc-radiopharmaceuticals. Methods The high purity molybdenum natural target (130 mg/cm2) was irradiated in a Cyclone 30 accelerator using 160 µA of 25 MeV proton beam energy for 1000 µA-h. After dissolution, the technetium radionuclides were extracted using methyl ethyl ketone (MEK) followed by preparation of Tc-MIBI, Tc-DTPA, Tc-DMSA and Tc-phytate as radiopharmaceutical samples. Results The results of quality controls and animal biodistribution studies showed successful production of Tc radionuclides (including 99mTc) in the bombarded target and subsequent labelling of the kit with Tc. Conclusion The developed high power Mo target if constructed using enriched 100Mo, could be a practical method for large-scale production of 99mTc and promising as an alternative to fission product 99Mo-99mTc generators for local applications near cyclotron facilities. PMID:22615656

  3. Re-thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals.

    Science.gov (United States)

    Notni, Johannes; Wester, Hans-Jürgen

    2017-11-16

    The potential and future role of certain metal radionuclides, for example, 44 Sc, 89 Zr, 86 Y, 64 Cu, 68 Ga, 177 Lu, 225 Ac, and 213 Bi, and several terbium isotopes has been controversially discussed in the past decades. Furthermore, the possible benefits of "matched pairs" of isotopes for tandem applications of diagnostics and therapeutics (theranostics) have been emphasized, while such approaches still have not made their way into routine clinical practice. Analysis of bibliographical data illustrates how popularity of certain nuclides has been promoted by cycles of availability and applications. We furthermore discuss the different practical requirements for diagnostic and therapeutic radiopharmaceuticals and the resulting consequences for efficient development of clinically useful pairs of radionuclide theranostics, with particular emphasis on the underlying economical factors. Based on an exemplary assessment of overall production costs for 68 Ga and 18 F radiopharmaceuticals, we venture a look into the future of theranostics and predict that high-throughput PET applications, that is, diagnosis of frequent conditions, will ultimately rely on 18 F tracers. PET radiometals will occupy a niche in the clinical low-throughput sector (diagnosis of rare diseases), but above all, dominate preclinical research and clinical translation. Matched isotope pairs will be of lesser relevance for theranostics but may become important for future PET-based therapeutic dosimetry. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Direct Technetium radiopharmaceuticals production using a 30MeV Cyclotron

    Directory of Open Access Journals (Sweden)

    M Kamali Dehgan

    2011-07-01

    Full Text Available Background and purpose of the study: Technetium-99m is the major radionuclide used in the world and mainly is provided by fission product. However extensive research has been conducted on the use of accelerators for production of 99mTc. This investigation reports the production of 99mTc radioisotope using cyclotrons followed by the preparation, quality control and biodistribution studies of four major Tc-radiopharmaceuticals. Methods: The high purity molybdenum natural target (130mg/cm2 was irradiated in a Cyclone 30 accelerator using 160 µA of 25 MeV proton beam energy for 1000 µA-h. After dissolution, the technetium radionuclides were extracted using methyl ethyl ketone (MEK followed by preparation of Tc-MIBI, Tc-DTPA, Tc-DMSA and Tc-phytate as radiopharmaceutical samples. Results: The results of quality controls and animal biodistribution studies showed successful production of Tc radionuclides (including 99mTc in the bombarded target and subsequent labelling of the kit with Tc. Conclusion: The developed high power Mo target if constructed using enriched 100Mo, could be a practical method for large-scale production of 99mTc and promising as an alternative to fission product 99Mo-99mTc generators for local applications near cyclotron facilities.

  5. KAERI's challenge to steady production of radioisotopes and radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Park, J.H.; Han, H.S.; Park, K.B. [Korea Atomic Energy Research Institute, Taejon (Korea)

    2000-10-01

    The Korea Atomic Energy Research Institute (KAERI) is a national organization in Korea, and has been doing many research and development works in radioisotope production and applications for more than 30 years. Now KAERI regularly produces radioisotopes (I-131, Tc-99m, Ho-166) for medical use and Ir-192 for industrial use. Various I-131 labeled compounds and more than 10 kinds of Tc-99m cold kits are also produced. Our multi-purpose reactor, named HANARO, has been operative since April of 1995. HANAKO is an open tank type reactor with 30 MW thermal capacity. This reactor was designed not only for research on neutron utilization but for production of radioisotopes. KAERI intended to maximize the radioisotope production capability. For this purpose, radioisotope production facilities (RIPF) have been constructed adjacent to the HANARO reactor building. There are four banks of hot cells equipped with manipulators and some of the hot cells were installed according to the KGMP standards and with clean rooms. In reviewing our RI production plan intensively, emphasis was placed on the development of new radiopharmaceuticals, development of new radiation sources for industrial and therapeutic use, and steady production of selected radioisotopes and radiopharmaceuticals. The selected items are Ho-166 based pharmaceuticals, fission Mo-99/Tc-99m generators. solution and capsules of I-131, and Ir-192 and Co-60 for industrial use. The status and future plan of KAERI's research and development program will be introduced, and will highlight programs for steady production. (author)

  6. Radiolabeling of trastuzumab with 177Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer.

    Science.gov (United States)

    Rasaneh, Samira; Rajabi, Hossein; Babaei, Mohammad Hossein; Daha, Fariba Johari; Salouti, Mojtaba

    2009-05-01

    Trastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical. Trastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line. The radiochemical purity of the complex was 96+/-0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93+/-1.2% and 85+/-3.5%, respectively. The immunoreactivity of the complex was 89+/-1.4%. At a concentration of 1 nM, the complex killed 70+/-3% of MCF7 cells. At 1.9 nM, 90+/-5% of the cells were killed. The results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer.

  7. Evaluation of radiochemical purities of some radiopharmaceuticals in Shiraz Namazi teaching hospital

    Directory of Open Access Journals (Sweden)

    Hossein Sadeghpour

    2015-03-01

    Full Text Available Many radiopharmaceuticals, as a special group of drugs, are eventually prepared at the nuclear medicine departments of the hospitals. Therefore, their quality control procedures such as sterility tests, radionuclide, radiochemical and chemical purity should be carried out in the hospitals. In this study, radiochemical purity for more than 300 preparations of three different radiopharmaceutical formulations from commercial kits were tested using instant thin layer chromatography. The formulations 99mTc-DTPA, 99mTc-MDP and 99mTc-MIBI were obtained from Pars Isotope Co. Several paper chromatographic systems including standard and factory recommended thin layer chromatography systems were used in this study. In addition different equipments for detection of radioactivity in paper chromatography like gamma camera and dose calibrator were used. The results showed that the most observed impurities were hydrolyzed reduced technetium (HR-Tc. There were no significant differences between calculated 99mTc-MIBI radiochemical purities when the radioactive detection device was gamma camera instead of dose calibrator. In case of 99mTc-DTPA and 99mTc-MDP, there were significant differences in detection of HR-Tc. On the contrary, no significant differences in free pertechnetate were observed when package insert procedures for quality control were used instead of those recommended in the references. Finally, we observed that the package insert procedures for quality control can offer higher radiochemical purities.

  8. Eighth report on survey of the adverse reaction to radiopharmaceuticals. 11th survey in 1985

    Energy Technology Data Exchange (ETDEWEB)

    1987-04-01

    Adverse reactions to radiopharmaceuticals occurring in the past one year from April 1, 1985 through March 31, 1986 are reported. Questionnaires were sent to 1,003 facilities, and 72% (722) responded. Twenty-seven adverse reactions and 9 drug defects were reported from a total of 29 facilities, giving an annual incidence of 2.7/100,000 and 0.9/100,000, respectively. The incidence of adverse reactions to I-131-6..beta..-iodomethyl-19-norcholesterol was the highest (242/100,000), followed by I-131 sodium iodohippurate (16/100,000), Tc-99m diethylenetriamine-pentaacetic acid (10/100,000), Ga-67 citrate (2/100,000), and Tc-99m pyrophosphate (2/100,000). Common adverse reactions included (a) reactions to the vagus nerves (n = 17), such as nausea, palpitation, and hypotension; (b) allergic reactions (n = 5), such as redness, itching, and dyspnea; and (c) others (n = 5), including back pain and tongue numbness. There was no fever. Radiopharmaceuticals reported as poor quality (drug defects) were Tc-99m Sn colloid, Tc-99m methylene diphosphonate, Tc-99m phytate, and Tc-99m generator. (Namekawa, K.).

  9. Active and passive vectorization of technetium{sup 99m} and {sup 188}rhenium radiopharmaceuticals for medical imaging and radiotherapy; Vectorisations active et passive de radiopharmaceutiques du technetium-99m et du rhenium-188 pour l'imagerie medicale et la therapie

    Energy Technology Data Exchange (ETDEWEB)

    Lepareur, N

    2003-11-15

    Research for new molecules for nuclear medicine is a field in constant development. Over the past few years, development of new radiopharmaceuticals for radiotherapy has renewed interest for rhenium chemistry. Indeed, its two isotopes {sup 186}Re and {sup 188}Re, owing to their ideal properties and their similitude with {sup 99m}Tc, which is widely used as a radiotracer for diagnostic imaging, seem very promising for the preparation of radiopharmaceuticals. In the first part of this manuscript, the synthesis of rhenium and technetium-99 complexes, [M(RPhCS3)2(RPhCS2)] (M = Re, Tc), is described. The preparation of technetium{sup 99m} based radiopharmaceuticals, analogues to the pondered complexes, is also described. The stability/reactivity of these complexes has been studied by exchange reactions with potential ligands, specially dithiocarbamates, and also by UV-visible absorption spectroscopy and thermogravimetry. The reactivity of the complexes towards dithiocarbamates leads to the possibility to bind biomolecules to the metallic core, via the dithiocarbamate moiety. This method represents a potential alternative to current ones using the so-called bifunctional approach. In the second part of this manuscript, a new kit formulation for the {sup 188}Re labeling of lipiodol is described, using a complex analogous to those described in the previous part. The labeled oil is a potential cure for hepatocellular carcinoma. The in vitro and in vivo stability of this {sup 188}Re-SSS lipiodol and of its analogue {sup 99m}Tc-SSS lipiodol has been studied, and also their in vivo behavior in healthy pigs. This study has shown the quasi-exclusive hepatic fixation of the radiopharmaceutical, and has proven its good stability. Its selectivity for tumors remains to be shown before trying it on humans. (author)

  10. An in vitro approach to evaluate and develop potential Sn-117m based bone-seeking radiopharmaceuticals

    NARCIS (Netherlands)

    Jansen, D.R.

    2010-01-01

    It has become standard practice in the development of radiopharmaceuticals to evaluate/assess the efficacy of prospective therapeutic or diagnostic agents by animal models, which generally calls for subjecting a substantial number of animals to intensive test and retest measurements for obtaining

  11. The good laboratory practice and good clinical practice requirements for the production of radiopharmaceuticals in clinical research

    NARCIS (Netherlands)

    De Vos, FJ; De Decker, M; Dierckx, RA

    Radiopharmaceuticals account for more than 95% of the group of sterile pharmaceutical products and should therefore be handled and produced with care. Since the introduction of the European directive, all pharmaceuticals used in clinical studies must be prepared under good manufacturing practice

  12. Radiopharmaceuticals preparation following hygienic rule; Preparation des radiopharmaceutiques dans le respect des regles d'hygiene

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand-Barat, J.; Rogues, A.M. [Hopital Pellegrin, 33 - Bordeaux (France); Brunet-Desruet, M.D. [Centre Hospitalier Universitaire, 38 - Grenoble (France); Couret, I. [Centre Hospitalier Universitaire, 34 - Montpellier (France). Hopital Lapeyronnie; Fraysse, M. [Hopital-CHG, 03 - Montlucon (France); Saurat, S.; Tafani, M. [Centre Hospitalier Universitaire Purpan, 31 - Toulouse (France); Bounaud, M.P. [Centre Hospitalier Universitaire, Jean Bernard, 86 - Poitiers (France); Fialdes, P. [Centre Hospitalier Universitaire, 59 - Lille (France). Hopital Salengro

    1999-03-01

    The rules of radiation protection are essential in a service of nuclear medicine. A sensitization to hygiene in hospital in front of the fresh outbreak of nosocomial infections is useful in order to optimize the quality approach. In this context, the preparation of radiopharmaceuticals in the structure of nuclear medicine deserves a specific reflection. (N.C.)

  13. Quality control on radiochemical purity in Technetium-99m radiopharmaceuticals labelling: three years of experience on 2280 procedures.

    Science.gov (United States)

    Maioli, Claudio; Luciniani, Giovanni; Strinchini, Aldo; Tagliabue, Luca; Del Sole, Angelo

    2017-04-28

    the purpose of this study was to offer an example of evaluations of the ISO9001 certified internal quality assurance (QA) system of 99mTc-radiopharmaceutical preparations and quality control in vivo use, using industrial kits and generators in order to identify possible sources of errors in the procedures labeling and quality control procedures. The study was performed at a single institution over a period of three years (July 1st, 2011 - July 1st, 2014), and included a total of 2280 radiopharmaceutical preparations prepared by four different technologists. All the radiopharmaceutical preparations and quality controls were performed according to each SPC provided by the manufacturer. The radiopharmaceutical preparations were the following (trade names are reported in brackets): 99mTc-albumin colloid [Nanocoll] (n=349), 99mTc-oxidronate [Technescan®hdp] (n=701), 99mTc-exametazime [Ceretec] (n=169), 99mTc-sestamibi [Cardiolite] (n=92), 99mTc-albumin aggregated [Technescan®lyomaa] (n=140), 99mTc-tetrofosmin [Myoview]) (n=567), 99mTc-diethylene triamine pentacetic acid [Technescan®dtpa] (n=254), and 99mTc-dimercapto succinic acid [Renocis®] (n=8). Data were analyzed to determine the number and type of radiopharmaceutical labelling failure and to derive the sources of these failures to define corrective actions and optimize the quality assurance program. A total of 2280 procedures were performed and recorded. Following the quality control procedure six out of the 2280 preparations (0.26%) were non-conforming for clinical use with the RCP limits indicated in the SPC. Five of these were due to gross technical errors in measurements and manual procedures and were immediately repeated, returning within the limits of acceptability. The sixth failure was due to short incubation time, though compliant with the manufacturer's instructions. We concluded that the quality of the final product depends on a controlled production system based on the implementation of specific

  14. Quality assessment of radiopharmaceuticals in nuclear medicine services at Northeast states, Brazil; Avaliacao da qualidade de radiofarmacos em servicos de medicina nuclear de estados da regiao nordeste

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Wellington Gomes de

    2012-07-01

    The radiopharmaceuticals are used in the field nuclear medicine services (NMS) as tracer in the diagnoses and treatment of many diseases. Radiopharmaceuticals used in nuclear medicine and usually have a minimum of pharmacological effect. The procedures for labelling Radiopharmaceuticals should be observed in order to minimize risks to patients, employees and individuals from the public, and to be administered in humans, must be sterile and free of pyrogens and possess elements all measures of quality controls required a conventional drug. The 'Agencia Nacional de Vigilancia Sanitaria (ANVISA)' in its 'Resolucao de Diretoria Colegiada' (RDC) No. 38 of June 4{sup th} 2008, decided that the NMS must perform quality control in the generators eluate and radiopharmaceuticals according to recommendations of manufacturers and scientific evidence accepted by ANVISA. Thus, this study proposes to evaluate the quality of the generator {sup 99M}o-{sup 99m}Tc eluate and radiopharmaceuticals labeled with {sup 99m}Tc used in most NMS of some states in the Northeast, in relation to radionuclide, chemical, radiochemical purity and pH and promote the inclusion of procedure for quality control of radiopharmaceuticals in routine NMS. The results show that 90% radionuclidic purity, 98.2% purity chemical and radiochemical purity of 46% and 100% of the eluates are in agreement with international pharmacopoeias; already radiopharmaceuticals showed 82.6% purity and all radiochemical pH values are also in accordance with international pharmacopoeias. Even with so many positive results, staff the majority of MNS was not able to perform the quality control of the eluates and radiopharmaceuticals. Showing the importance of implementing of quality control programs of the eluates and radiopharmaceuticals in nuclear medicine. (author)

  15. In vitro study of tumor seeking radiopharmaceutical uptake by human breast cancer cell line MCF-7 after paclitaxel treatment

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Joon Young; Choi, Yong; Choe, Yearn Seong; Lee, Kyung Han; Kim, Byung Tae [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2007-10-15

    This study was designed to investigate the cellular uptake of various tumor imaging radiopharmaceuticals in human breast cancer cells before and after paclitaxel exposure considering viable cell number. F-18-fluorodeoxyglucose, C-11-methionine. TI-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin were used to evaluate the cellular uptake in MCF-7 cells. MCF-7 cells were cultured in multi-well plates. Wells were divided into DMSO exposure control group, and paclitaxel exposure group. The exposure durations of paclitaxel with 10 nM or 100 nM were 2 h, 6 h, 12 h, 24 h, and 48 h. Viable cell fraction was reduced as the concentration and exposure time of paclitaxel increased. After 10 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was not reduced significantly, irrespective of exposure time and viable cell fraction. After 100 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was enhanced significantly irrespective of viable cell fraction. The peak uptake was observed in experimental groups with paclitaxel exposure for 6 to 48 h according the type of radiopharmaceutical. When the cellular uptake was adjusted for the viable cell fraction and cell count, the peak cellular uptake was observed in experimental groups with paclitaxel exposure for 48 h, irrespective of the type of radiopharmaceutical. The cellular uptake of F-18-fluorodeoxyglucose, C-11-methionine, TI-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin did not reflect viable cell number in MCF-7 cells after paclitaxel exposure for up to 48 h.

  16. Determination of radiochemical yield of {sup 99m}Tc radiopharmaceutical preparations using gamma counter and linear radiochromatography scanner

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Patricia de A.; Moura, Rebeca G.; Shiki, Andressa M.; Fukumori, Neuza T.O.; Matsuda, Margareth M.N., E-mail: patyosborne@yahoo.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    The radiochemical purity (RCP) evaluation is a prerequisite for radiopharmaceuticals before the administration in patients. RCP is defined as the proportion of the total radioactivity in the product that is present in the specified chemical form. The most widely used techniques for RCP determination in radiopharmaceutical preparations are thin layer chromatography (TLC-Al), instant thin layer chromatography (ITLC-SG) and paper chromatography (PC). These techniques combined with radioactivity detection are one of the most important tools in the RCP of the radiopharmaceutical compounds. Several methods are used for the determination of the spatial distribution of radioactivity on the strips. The aim of this study was to compare two methods for radioactivity measurement in the determination of RCP in {sup 99m}Tc radiopharmaceuticals using gamma counter and linear radiochromatography scanner. Lyophilized radiopharmaceuticals were labeled with {sup 99m}Tc. The analysis was carried out using TLC-Al and high performance thin layer chromatography (HPTLC-Cellulose) sheets, ITLC-SG and 3MM Whatman PC. The radioactivity distribution was determined by counting each strip during 1 minute in a radiochromatography TLC scanner. For comparison, the strips were cut into small pieces and each one was separately measured in a gamma-counter during 0.20 minutes in 70-210 KeV {sup 99m}Tc window. USP 36 and FDA specify that not less than 90% of the total radioactivity must be in the spot corresponding to {sup 99m}Tc labeled compound. In conclusion, the procedure for RCP determination of ALBUMINA-TEC, DEX500-TEC, ECD-TEC, MACRO-TEC and MIBI-TEC can be faster using radiochromatography. (author)

  17. Residual activities of 99mTc-labelled radiopharmaceuticals in routine nuclear medicine practice.

    Science.gov (United States)

    Stavrou, Petros Z; Papachristou, Maria; Persakis, Evangelos; Kouvelis, Konstantinos; Datseris, Ioannis E

    2016-06-01

    In this study, we present a series of common Tc-labelled radiopharmaceuticals administrations performed in a busy nuclear medicine department within a 1-year timeframe in routine practice. The main objective is to identify the true activity administered to the patient and whether that is in compliance with the EANM guidelines, where applicable, and/or with the department's protocols. As a secondary objective, we aimed to assess whether the volume of the injected dose correlates to the percentage of residual activity measured after injection for each studied radiotracer. A number of commonly used Tc-labelled radiopharmaceuticals including Tc-pertechnetate, Tc-methylenediphosphonic acid, Tc-hydroxymethylenediphosphonic acid, Tc-3,3-diphosphono-1,2-propanedicarboxylic acid, Tc-dimercaptosuccinic acid (DMSA), Tc-mercaptoacetyltriglycine, Tc-2-methoxyisobutylisonitrile (sestamibi), Tc-1,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) and Tc-HYNIC-Tyr-octreotide (Tektrotyd) were assessed. All data were collected prospectively within a 1-year period under routine medical practice and included (a) injected activity, (b) residual activity, (c) percentage of residual activity (residual activity/injected activity×100), (d) effective activity (injected activity minus the residual activity), (e) injected volume, (f) time of injection and (g) type of procedure. In the 1837 collected measurements, the average percentage of residual activity was 13% (95% confidence interval: 12.75-13.39%). The mean effective activities were within the recommended range by the EANM guidelines, where applicable, or did not exceed the recommended doses from the department's protocols. In cases where actual injected activity was lower than the minimum suggested by the department's protocols, the imaging quality was not compromised. There was a negative correlation and thus an inverse relationship between the percentage of residual activity and administered volume for Tc-pertechnetate, Teceos

  18. Generators and automated generator systems for production and on-line injections of pet radiopharmaceuticals

    Science.gov (United States)

    Shimchuk, G.; Shimchuk, Gr; Pakhomov, G.; Avalishvili, G.; Zavrazhnov, G.; Polonsky-Byslaev, I.; Fedotov, A.; Polozov, P.

    2017-01-01

    One of the prospective directions of PET development is using generator positron radiating nuclides [1,2]. Introduction of this technology is financially promising, since it does not require expensive special accelerator and radiochemical laboratory in the medical institution, which considerably reduces costs of PET diagnostics and makes it available to more patients. POZITOM-PRO RPC LLC developed and produced an 82Sr-82Rb generator, an automated injection system, designed for automatic and fully-controlled injections of 82RbCl produced by this generator, automated radiopharmaceutical synthesis units based on generated 68Ga produced using a domestically-manufactured 68Ge-68Ga generator for preparing two pharmaceuticals: Ga-68-DOTA-TATE and Vascular Ga-68.

  19. Overview and perspectives on automation strategies in (68)Ga radiopharmaceutical preparations.

    Science.gov (United States)

    Boschi, Stefano; Malizia, Claudio; Lodi, Filippo

    2013-01-01

    The renaissance of (68)Ga radiopharmacy has led to great advances in automation technology. The availability of a highly efficient, reliable, long-lived (68)Ge/(68)Ga generator system along with a well-established coordination chemistry based on bifunctional chelating agents have been the bases of this development in (68)Ga radiopharmacy. Syntheses of (68)Ga peptides were originally performed by manual or semiautomated systems, but increasing clinical demand, radioprotection, and regulatory issues have driven extensive automation of their production process. Several automated systems, based on different post-processing of the (68)Ga generator eluate, on different engineering, and on fixed tubing or disposable cassette approaches, have been developed and are discussed in this chapter. Since automatic systems for preparation of radiopharmaceuticals should comply with qualification and validation protocols established by regulations such as current Good Manufacturing Practices (cGMP) and local regulations, some regulatory issues and the more relevant qualification protocols are also discussed.

  20. Pixelated scintillator-based compact radio thin layer chromatography scanner for radiopharmaceuticals quality control

    Science.gov (United States)

    Jeon, S. J.; Kim, K. M.; Lim, I.; Song, K.; Kim, J. G.

    2017-11-01

    We evaluated a compact and cost-effective radio thin-layer chromatography (radio-TLC) scanner for the quality control (QC) of radiopharmaceuticals. We adapted a scintillation detector, which is a Gd3Al2Ga3O12 (GAGG:Ce) scintillation crystal array coupled with a photodiode array. The performance of the scintillator array-based radio-TLC was compared with that of a commercial device. We scanned 1 μCi/μL of Tc-99m and F-18 with each device. The difference between the ROI count ratios of the developed and commercial scanners was less than 1.2%. Our scanner is sensitive enough to take measurements for a radiochemical purity test.

  1. External radiation doses from patients administered with radiopharmaceuticals measurements and Monte Carlo simulation

    Directory of Open Access Journals (Sweden)

    Kinsara Abdul Raheem

    2014-01-01

    Full Text Available Monte Carlo simulations and dose measurements were performed for radionuclides in the whole body and trunks of different sizes in order to estimate external radiation whole body doses from patients administered with radiopharmaceuticals. Calculations were performed on cylindrical water phantoms whose height was 176 cm and for three body diameters: of 24 cm, 30 cm, and 36 cm. The investigated radionuclides were: 99mTc, 131I, 23I, 67Ga, 201Tl, and 111In. Measured and MCNP-calculated values were 2-6 times lower than the values calculated by the point source method. Additionaly, the total dose received by the public until a radionuclide is completely disintegrated was calculated. The other purpose of this work is to provide data on whole body and finger occupational doses received by technologists working in nuclear medicine. Data showed a wide variation in doses that depended on the individual technologist and the position of the dosimeter.

  2. Scaling animal to human biodistribution of the radiopharmaceutical [68Ga]Ga-PSMA-HBED-CC

    Energy Technology Data Exchange (ETDEWEB)

    Parra, Pamela Ochoa, E-mail: lapochoap@unal.edu.co; Veloza, Stella [Grupo de Física Nuclear, Departamento de Física, Universidad Nacional de Colombia, Bogota, D.C. (Colombia)

    2016-07-07

    The radiotracer called {sup 68}Ga-labelled Glu-urea-Lys(Ahx)-HBED-CC ([68Ga]Ga-PSMA-HBED-CC) is a novel radiophar-maceutical for the detection of prostate cancer lesions by positron emission tomography (PET) imaging. Setting up a cost-effective manual synthesis of this radiotracer and making its clinical translation in Colombia will require two important elements: the evaluation of the procedure to yield a consistent product, meeting standards of radio-chemical purity and low toxicity and then, the evaluation of the radiation dosimetry. In this paper a protocol to extrapolate the biokinetic model made in normal mice to humans by using the computer software for internal dose assessment OLINDA/EXM® is presented as an accurate and standardized method for the calculation of radiation dosimetry estimates.

  3. Effect of altered thyroid status on the transport of hepatobiliary radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Pahuja, D.N.; Noronha, O.P.

    1985-10-01

    The effect of induced hypothyroidism (by feeding an antithyroid drug-propylthiouracil) on the transport and clearance of the routinely used hepatobiliary radiopharmaceuticals--radioiodinated iodine- T (131I) rose bengal and technetium-99m-N-(4-n-butylphenylcarbamoylmethyl) iminodiacetate, was studied in the rats. Hypothyroidism was associated with depressed growth and retarded clearance of these radiotracers from the in vivo system. Treatment of the hypothyroid rats with thyroxine (2-5 micrograms/100 g b.w. day) for 6 wk, restored these parameters towards normal values. These data suggest that delayed clearance of these hepatobiliary tracers could be related to reduced metabolic rate accompanied with the hypotonia and hypomotility of intestine normally observed in the hypothyroid state.

  4. Influence of radiation on endotoxin test using the PTSTM for 18-FDG radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Santos-Oliveira, Ralph, E-mail: roliveira@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Radiofarmacia

    2010-07-15

    F-18 FDG (2-[18-F] fluoro-2-deoxy-D-glucose) is the most frequently used radiopharmaceutical for PET and PET CT imaging exams. The FDA recently approved the use of the PTS{sup TM} (Portable Test System) as an alternative to the standard test proposed by the United States Pharmacopeia using the LAL (Limulus Amebocyte Lysates), that takes longer to perform (about 1h) than the PTS{sup TM} (15 min). Recent studies have demonstrated that radiation could interfere with the PTS{sup TM} test. In order to study the effects of radiation on the PTS{sup TM} test and/or equipment, 27 batches of F-18 FDG produced in the Nuclear Engineering Institute were analyzed. The results showed that no direct correlation with radiation was found in any of the cases. (author)

  5. High--valent technetium chemistry-new opportunities for radiopharmaceutical developments.

    Science.gov (United States)

    Braband, Henrik

    2014-04-01

    The rich coordination chemistry of (99m) Tc distinguishes this radiometal from other radiolabels applied for single-photon emission computed tomography (SPECT) or positron emission tomography (PET). This potential should be used to create novel opportunities for the development of effective imaging probes. In this context, the field of high-valent technetium chemistry has received much interest. It has been shown that fac-{(99m) TcO3 }(+) complexes are potential new synthons for radiopharmaceutical developments, due to their unique physicochemical properties and unprecedented reactivity. In this article, recent developments and the 'state of the art' in this field of technetium chemistry will be reviewed comprehensively. Copyright © 2013 John Wiley & Sons, Ltd.

  6. PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments

    Directory of Open Access Journals (Sweden)

    Roland Haubner

    2014-01-01

    Full Text Available Noninvasive determination of integrin expression has become an interesting approach in nuclear medicine. Since the discovery of the first 18F-labeled cyclic RGD peptide as radiotracer for imaging integrin αvβ3 expression in vivo, there have been carried out enormous efforts to develop RGD peptides for PET imaging. Moreover, in recent years, additional integrins, including α5β1 and αvβ6, came into the focus of pharmaceutical radiochemistry. This review will discuss the tracers already evaluated in clinical trials and summarize the preliminary outcome. It will also give an overview on recent developments to further optimize the first-generation compounds such as [18F]Galacto-RGD. This includes recently developed 18F-labeling strategies and also new approaches in 68Ga-complex chemistry. Furthermore, the approaches to develop radiopharmaceuticals targeting integrin α5β1 and αvβ6 will be summarized and discussed.

  7. Evaluation of alternative rapid thin layer chromatography systems for quality control of technetium-99m radiopharmaceuticals.

    Science.gov (United States)

    Mang'era, Kennedy; Wong, Derek; Douglas, David; Franz, Kellie; Biru, Taddese

    2014-04-01

    Whatman 3MM™ and Tec-Control™ systems were evaluated as ITLC-SG alternatives for 99mTc-radiopharmaceuticals. They compare well in accuracy and reproducibility, and are faster and more convenient than ITLC-SG. Tec-Control™ radiochemical purity values for 99mTc-sestamibi were more conservative than ITLC-SG. Full solvent migration was not reproduced for 99mTc-tetrofosmin in Tec-Control™, and for this Whatman 3MM™ is preferred. Developing times were 10-15 min, 7-9 min and ~1min for ITLC-SG, Whatman 3MM™ and Tec-Control™, respectively. Overall, Tec-Control™ strips are preferred due to speed and ease of use. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Cage-like bifunctional chelators, copper-64 radiopharmaceuticals and PET imaging using the same

    Energy Technology Data Exchange (ETDEWEB)

    Conti, Peter S.; Cai, Hancheng; Li, Zibo; Liu, Shuanglong

    2016-08-02

    Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.

  9. Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Thomas L. Mindt

    2013-03-01

    Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

  10. Deficiencies in product labelling instructions and quality control directions for 99mTc radiopharmaceuticals.

    Science.gov (United States)

    Buroni, Federica E; Lodola, Lorenzo; Persico, Marco G; Aprile, Carlo

    2014-02-01

    The aim of the study was to identify deficiencies in product labelling instructions for reconstitution and in the quality control directions detailed in the technical leaflets (TLs) or summary product characteristic (SPC) sheets of commonly used technetium labelling cold kits. The reconstitution and quality control directions in 25 TLs/SPCs were evaluated to identify deficiencies, incompleteness, restrictions, errors, impracticability, and vagueness. In addition, their congruence with the statements given in the relative European Pharmacopoeia (Ph. Eur. VII ed.) monography and diagnostic reference levels of Directive 97/43/EURATOM was evaluated. Deficiencies in information were scored and classified into five categories: 1, absent or incomplete; 2, restrictive; 3, inconsistent or wrong; 4, impractical; and 5, vague. In the 25 documents analyzed a total of 141 deficiencies were found (corresponding to 40.2% of the total scores assigned), and more frequently they pertained to quality control procedures (70.9%), followed by those related to quantitative composition (14.9%), preparation (8.5%), and particle size (5.7%). Nearly 80% of these deficiencies were classified as type 1 - that is, absent or incomplete information. The indications in TLs and SPCs should provide useful information for maintaining the quality and purity of the radiopharmaceutical preparation and ensure the safety level and effectiveness required by law. However, the instructions are often suboptimal or even erroneous, and consequently there are countless failures or difficulties, which represent an impediment to good laboratory practice. We believe that a 'smart' review of radiopharmaceutical documentation would be beneficial in order to align these indications to the real needs of the operators involved in routine in-house nuclear medicine practice.

  11. Advances in the production of isotopes and radiopharmaceuticals at the Atomic Energy Corporation of South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Louw, P.A.; De Villiers, W.Y.Z.; Jarvis, N.V. [Atomic Energy Corporation of South Africa Ltd, Pretoria (South Africa)

    1997-10-01

    The Atomic Energy Corporation of South Africa Ltd (AEC) owns and operates the 20 MW research reactor, SAFARI-1. Utilisation of the reactor has in recent years changed from research and materials testing to the production of isotopes. The most important breakthrough achieved in recent years is the production of high quality fission 99Mo. This has been produced routinely since April 1993 and supplied to clients across the world. A capability for the reliable production of 1000 Ci of 99Mo per week (calibrated for six days after production) has been proven. The AEC has also established facilities to produce its own 99mTc generators together with a most of radiopharmaceutical kits for diagnostic nuclear medicine purposes. The production of {sup 153}Sm and {sup 131}I (tellurium oxide route) has been operational for many years. Applications include therapeutic radiopharmaceuticals such as {sup 153}Sm-EDTMP for bone cancer pain palliation, {sup 13`}I-Lipiodol for liver cancer and {sup 131}I capsules for thyroid treatment. Facilities for the production of other isotopes such as {sup 131}I (from fission), {sup 32}P and {sup 35}S are in various stages of completion. Extensive analytical methods and equipment have been developed and are routinely used to certify the quality of exported isotopes. Irradiation and encapsulation of {sup 192}Ir is also performed routinely at the AEC. Modern facilities allow for the production of isotopes such as {sup 131}Ba and {sup 140}La on an ad hoc basis. Quality assurance procedures based on ISO9000 were developed for all aspects of the production of the various isotopes. Documentation, such as Drug Master Files, required by authorities in various countries has also been submitted and accepted 15 refs., 1 tab., 2 figs.

  12. Effect of probenecid on renal excretion of three renal radiopharmaceuticals at 15 and 30 minutes

    Energy Technology Data Exchange (ETDEWEB)

    Antar, M.A.; Jones, A.N.

    1985-05-01

    The authors have developed and reported new renal TC-99m labeled agents (e.g. Tc-R-VII, a complex of Tc-99m and cystine) as potential replacements for I-131-orthoiodohippuran (OIH), which is the only radiopharmaceutical in routine use for evaluation of renal tubular function, but which has distinct limitations. The new agents have better renal uptake and faster excretion than the Tc-99m-DTPA in current use. To test whether Tc-R-VII is tubularly secreted, they studied the effect of the tubular inhibitor probenecid (P) on it, Tc-99m-DTPA, and OIH in male rabbits at 15 and 30 minutes. After i/v administration of buffered probenecid (100 mg/kg) over 20 minutes , or the buffer for control (C) animals, the radiotracer was intravenously injected. Mean urinary excretion as % dose was assayed. At 15 minutes, P showed no inhibition of DTPA excretion (P: 30.42 +- 8.00 and C: 27.5 +- 2.90). However, P inhibited Tc-R-VII excretion by 37%, which was similar to the inhibition demonstrated for OIH (33%). The inhibition for both compounds was significant at P<0.01. At 30 minutes, probenecid affected neither OIH nor DTPA excretion, while TC-R-VII was inhibited by 30%. These findings indicate that while the newly developed Tc-99m compound is secreted by renal tubules is a manner similar to I-131-OIH and has a promise as a renal radiopharmaceutical, the two compounds have some differences in their renal characteristics and require further study to elucidate the transport mechanisms involved.

  13. Implementation and validation of collapsed cone superposition for radiopharmaceutical dosimetry of photon emitters.

    Science.gov (United States)

    Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

    2015-10-21

    Two collapsed cone (CC) superposition algorithms have been implemented for radiopharmaceutical dosimetry of photon emitters. The straight CC (SCC) superposition method uses a water energy deposition kernel (EDKw) for each electron, positron and photon components, while the primary and scatter CC (PSCC) superposition method uses different EDKw for primary and once-scattered photons. PSCC was implemented only for photons originating from the nucleus, precluding its application to positron emitters. EDKw are linearly scaled by radiological distance, taking into account tissue density heterogeneities. The implementation was tested on 100, 300 and 600 keV mono-energetic photons and (18)F, (99m)Tc, (131)I and (177)Lu. The kernels were generated using the Monte Carlo codes MCNP and EGSnrc. The validation was performed on 6 phantoms representing interfaces between soft-tissues, lung and bone. The figures of merit were γ (3%, 3 mm) and γ (5%, 5 mm) criterions corresponding to the computation comparison on 80 absorbed doses (AD) points per phantom between Monte Carlo simulations and CC algorithms. PSCC gave better results than SCC for the lowest photon energy (100 keV). For the 3 isotopes computed with PSCC, the percentage of AD points satisfying the γ (5%, 5 mm) criterion was always over 99%. A still good but worse result was found with SCC, since at least 97% of AD-values verified the γ (5%, 5 mm) criterion, except a value of 57% for the (99m)Tc with the lung/bone interface. The CC superposition method for radiopharmaceutical dosimetry is a good alternative to Monte Carlo simulations while reducing computation complexity.

  14. Report on survey of the adverse reaction to radiopharmaceuticals. 16. The 19th survey in 1993

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-06-01

    This report deals with adverse reactions to radiopharmaceuticals occurring during the period from April 1, 1993 through March 31, 1994. Questionnaires were sent to 1,176 facilities, and 904 (76.9%) responded. A total of 8 cases of adverse reactions and 16 cases of drug defect were reported from 22 (2.4%) of the 904 facilities, giving an annual occurrence of 0.7 and 1.4 cases, respectively, for 100,000 examinations. The present data provided the lowest incidence of adverse reactions, compared with the previous data for 5 years. The incidence of drug defect also tended to be decreased. The incidence of adverse reactions for a total of 904 facilities was the highest for I-131-6{beta}-iodomethyl-19-norcholesterol (n=34), followed by {sup 99m}Tc-MIBI (n=16), {sup 99m}Tc-DTPA (n=4), {sup 99m}Tc-HM-PAO (n=4), {sup 99m}Tc-MAA (n=3), and {sup 201}Tl-chloride (n=1). Adverse reactions included reactions to the vagus nerves (n=4), allergic reactions (n=3), and others (n=1). Radiopharmaceutical reported as drug defect were as follows: {sup 99}Mo-{sup 99m}Tc-generator, {sup 99m}Tc-phytate, {sup 99m}Tc-HMDP, {sup 99m}DMSA, {sup 99m}Tc-HM-PAO, {sup 67}Ga citrate, {sup 123}I-BMIPP, {sup 131}I-sodium iodide capsule for treatment, {sup 111}In-iridium chloride, and {sup 133}Xe-xenogas. (N.K.).

  15. Report on survey of the adverse reaction to radiopharmaceuticals, 12; The 15th survey in 1989

    Energy Technology Data Exchange (ETDEWEB)

    1991-04-01

    This is the 12th report concerning adverse reactions to radiopharmaceuticals occurring during the period from April 1, 1989 through March 31, 1990. Questionnaires were sent to 1,111 facilities, and 827 (74.4%) responded. Twenty two cases of adverse reactions and 10 cases of drug defect were reported from a total of 29 facilities (3.5%), giving an annual occurrence of 2.4 cases and 1.1 cases, respectively, for 100, 000 examinations. The incidence of adverse reactions was the highest for I-131-6B-iodomethyl-19-norcholesterol (184 cases/100,000 examinations), followed by I-131 sodium hippurate (22), Tc-99m HSA-DTPA (20), Tc-99m HM-PAO (13), Tc-99m pyrophosphate and Tc-99m DTPA (8), and Tl-201 thallium chloride and I-123 IMP (2). Adverse reactions included reactions to the vagus nerves (n=10), allergic reactions (n=6), and others (n=6); they were characterized by face or skin redness and nausea or vomiting induced by Tc-99m pyrophosphate, eruptions 5 hr after Tl-201 thallium chloride injection, and symptoms following the injection of Tc-99m HM-PAO, I-123 IMP, and Tc-99m HSA-DTPA. Radiopharmaceuticals reported as drug defects were as follows: Tc-99m MDP, Tc-99m tin colloid, Tl-201 thallium chloride, Tc-99m MAA, Tc-99m HMDP, Tc-99m HM-PAO, Xe-133 gas, and Tc-99m generator. (N.K.).

  16. 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.

  17. Considerations of radiation protection by the use of a new radiopharmaceutical in metabolic therapy; Consideraciones de proteccion radiologica por la utilizacion de un nuevo radiofarmaco en terapia metabolica

    Energy Technology Data Exchange (ETDEWEB)

    Esteve, S.; Sanchez, K.; Prieto, D.; Rodriguez, P.; Diaz, E.; Barquero, R.; Ferrer, N.; Arranz, L.

    2013-07-01

    The use of high doses of radiopharmaceutical requires special measures for radiation protection and establishing protocols to minimize the dose of professionally exposed workers and family members who have to care for, or living with the patient treated. (Author)

  18. An in vitro approach to evaluate and develop potential Sn-117m based bone-seeking radiopharmaceuticals

    OpenAIRE

    Jansen, D.R.

    2010-01-01

    It has become standard practice in the development of radiopharmaceuticals to evaluate/assess the efficacy of prospective therapeutic or diagnostic agents by animal models, which generally calls for subjecting a substantial number of animals to intensive test and retest measurements for obtaining representative and conclusive results/data. This work communicates the advantage of combining various analytical modalities with mathematical and computational modeling as a multifaceted tool, for pr...

  19. Caution to HPLC analysis of tricarbonyl technetium radiopharmaceuticals: an example of changing constitution of complexes in column.

    Science.gov (United States)

    Chen, Xiangji; Guo, Yunhang; Liu, Boli

    2007-03-12

    Radio-HPLC is a powerful tool for analyzing radioactive species in radiopharmaceutical chemistry. In this paper, we found an example that the commonly used eluting solvent, acetonitrile, could coordinate with the popular radiopharmaceutical nuclides, technetium-99m, during chromatography. [(99m)Tc(CO)(3)(H(2)O)(3)](+) and [Re(CO)(3)(H(2)O)(3)](+) showed quite different retention time when they were eluted using acetonitrile/water as mobile phase. However, they almost demonstrated the same retention time when they were eluted using methanol/water as mobile phase. Further analysis showed that both [(99m)Tc(CO)(3)(H(2)O)(3)](+) and [Re(CO)(3)(H(2)O)(3)](+) could be changed into [(99m)Tc(CO)(3)(CH(3)CN)(3)](+) and [Re(CO)(3)(CH(3)CN)(x)(H(2)O)(3-x)](+) during the separation, respectively. Some former works mistook the [(99m)Tc(CO)(3)(CH(3)CN)(3)](+) for [(99m)Tc(CO)(3)(H(2)O)(3)](+) when using acetonitrile and water in analysis. Quality control of the radiopharmaceuticals containing metal complex should be careful since HPLC solvent could replace some liable ligand molecules.

  20. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Zeltchan, R., E-mail: r.zelchan@yandex.ru; Medvedeva, A.; Sinilkin, I.; Chernov, V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Stasyuk, E.; Rogov, A.; Il’ina, E.; Larionova, L.; Skuridin, V. [Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with {sup 99m}Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of {sup 99m}Tc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with {sup 99m}Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of {sup 99m}Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with {sup 99m}Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of {sup 99m}Tc-1-thio-D-glucose at the tumor site. The accumulation of {sup 99m}Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that {sup 99m}Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of {sup 99m}Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  1. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    Science.gov (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

    2016-08-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  2. Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis

    Science.gov (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.

    2016-06-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  3. Noninvasive measurement of radiopharmaceutical time-activity data using external thermoluminescent dosimeters (TLDs)

    Science.gov (United States)

    Lu, Cheng-Chang; Dong, Shang-Lung; Lin, Hsin-Hon; Ni, Yu-Ching; Jan, Meei-Ling; Chuang, Keh-Shih

    2017-02-01

    In this study, we present a new method for estimating the time-activity data using serial timely measurements of thermoluminescent dosimeters (TLDs). The approach is based on the combination of the measurement of surface dose using TLD and Monte Carlo (MC) simulation to estimate the radiopharmaceutical time-activity data. It involves four steps: (1) identify the source organs and outline their contours in computed tomography images; (2) compute the S values on the body surface for each source organ using a MC code; (3) obtain a serial measurement of the dose with numerous TLDs placed on the body surface; (4) solve the dose-activity equation to generate organ cumulative activity for each period of measurement. The activity of each organ at the time of measurement is simply the cumulative activity divided by the timespan between measurements. The usefulness of this method was studied using a MC simulation based on an Oak Ridge National Laboratory mathematical phantom with 18F-FDG filled in six source organs. Numerous TLDs were placed on different locations of the surface and were repeatedly read and replaced. The time-activity curves (TACs) of all organs were successfully reconstructed. Experiments on a physical phantom were also performed. Preliminary results indicate that it is an effective, robust, and simple method for assessing the TAC. The proposed method holds great potential for a range of applications in areas such as targeted radionuclide therapy, pharmaceutical research, and patient-specific dose estimation.

  4. Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters.

    Science.gov (United States)

    Wieder, Hinrich A; Lassmann, Michael; Allen-Auerbach, Martin S; Czernin, Johannes; Herrmann, Ken

    2014-07-28

    Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer. Different radionuclides that emit β-rays such as (153)Samarium and (89)Strontium and achieve palliation are commercially available. In contrast to β-emitters, (223)Radium as a α-emitter has a short path-length. The advantage of the α-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms. Due to the limited range of the α-particles the bone surface to red bone marrow dose ratio is also lower for (223)Radium which is expressed in a lower myelotoxicity. The α emitter (223)Radium dichloride is the first radiopharmaceutical that significantly prolongs life in castrate resistant prostate cancer patients with wide-spread bone metastatic disease. In a phase III, randomized, double-blind, placebo-controlled study 921 patients with castration-resistant prostate cancer and bone metastases were randomly assigned. The analysis confirmed the (223)Radium survival benefit compared to the placebo (median, 14.9 mo vs 11.3 mo; P US Food and Drug Administration.

  5. Patient dose reduction by changing the amount of {sup 18}F-FDG radiopharmaceutical injected

    Energy Technology Data Exchange (ETDEWEB)

    Paiva, Fernanda G. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear. Programa de Pós Graduação em Ciências e Técnicas Nucleares; Santana, Priscila C. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Anatomia e Imagem; Mourão Filho, Arnaldo P., E-mail: fgpaiva92@gmail.com, E-mail: pridili@gmail.com, E-mail: apratabhz@gmail.com [Centro Federal de Educação Tecnológica de Minas Gerais (CEFET-MG), Belo Horizonte, MG (Brazil). Centro de Engenharia Biomédica

    2017-07-01

    Images of Positron Emission Tomography (PET) associated with Computed Tomography (CT) have important diagnostic applications, mainly for oncology. These compound tomographic devices allow the overlapping of functional images obtained from the administration of radiopharmaceuticals and anatomical images generated by X-ray beam attenuation. This work evaluated the impact of reducing the effective dose by reducing the activity injected into the patient using the ICRP 106 biokinetic model. The activity to be injected may vary according to the patient mass and the detector sensitivity. In this work was used the fixed mass of Alderson phantoms, as a standard adult, this mass is 73.5 kg for the male, and 50 kg for the female. Different values of activity to be injected were simulated, from 0.07 mCi to 0.15 mCi, and with 10 mCi, protocol used in some services. Thus, for the acquisition of PET scans, any reduction of the administered activity implies a proportional reduction of the effective dose in patient. The effective dose may vary up to 114% altering the injected activity between 0.07 and 0.15 mCi. Comparing the results found for the effective dose range using 10 mCi the effective dose may vary by up to approximately 14000%. It is expected that the PET/CT scans protocols are changed at the end of the study, so that the absorbed and effective dose received by the patient decreases. (author)

  6. Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats.

    Science.gov (United States)

    Holanda, Cecília Maria de Carvalho Xavier; Barbosa, Delianne Azevedo; Demeda, Vanessa Fávero; Bandeira, Flora Tamires Moura; Medeiros, Hilkéa Carla Souza de; Pereira, Kércia Regina Santos Gomes; Barbosa, Vanessa Santos de Arruda; Medeiros, Aldo Cunha

    2014-03-01

    To evaluate the effect of hydroalcoholic extract of A. muricata on biodistribution of two radiopharmaceuticals: sodium phytate and dimercaptosuccinic acid (DMSA), both labeled with 99mtechnetium. Twenty four Wistar rats were divided into two treated groups and two controls groups. The controls received water and the treated received 25mg/kg/day of A. muricata by gavage for ten days. One hour after the last dose, the first treated group received 99mTc-DMSA and the second sodium 99mTc-phytate (0.66MBq each group), both via orbital plexus. Controls followed the same protocol. Forty min later, all groups were sacrificed and the blood, kidney and bladder were isolated from the first treated group and the blood, spleen and liver isolated from the second treated group. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated using a gamma counter. The statistical analysis showed that there was a statistically significant decrease (pmuricata hydroalcoholic extract negatively influenced the uptake of 99mTc-DMSA in bladder, kidney and blood of rats.

  7. Present status of research on Re-186 radiopharmaceuticals at Radioisotope Production Center

    Energy Technology Data Exchange (ETDEWEB)

    Mutalib, A. [Radioisotope Production Center, National Atomic Energy Agency Kawasan PUSPIPTEK, Serpong (Indonesia)

    1998-10-01

    Rhenium shows a close chemical similarity to technetium and is suitable for radiotherapy because the {beta}-emitting radionuclides {sup 186}Re (t{sub 1/2} 90 h, E{sub {beta}} = 1.1 MeV, E{sub {gamma}} = 137 keV) and {sup 188}Re (t{sub 1/2} = 17 h, E{sub {beta}} = 2.1 MeV). The {gamma}-emission associated with decay of {sup 186}Re is also useful in scintigraphy. The research on {sup 186}Re radiopharmaceuticals at Radioisotope Production Center has been carried out since April 1997. Interest in radioimmunotherapy (RIT) led us to the development of labeling antibodies with rhenium isotopes. Although there are several methods for coupling radiometal to antibody, we prefer an indirect labeling method in which a bifunctional chelating agent is used for coupling of {sup 186}Re to monoclonal antibodies. In this report we outline the study on the preparation of {sup 186}Re DMSA-TFP as precursor for labeling with monoclonal antibody. (author)

  8. Development of a radiopharmaceutical dose calculator for pediatric patients undergoing diagnostic nuclear medicine studies.

    Science.gov (United States)

    Pandey, Anil Kumar; Sharma, Sanjay Kumar; Sharma, Punit; Gupta, Priyanka; Kumar, Rakesh

    2013-04-01

    It is important to ensure that as low as reasonably achievable (ALARA) concept during the radiopharmaceutical (RPH) dose administration in pediatric patients. Several methods have been suggested over the years for the calculation of individualized RPH dose, sometimes requiring complex calculations and large variability exists for administered dose in children. The aim of the present study was to develop a software application that can calculate and store RPH dose along with patient record. We reviewed the literature to select the dose formula and used Microsoft Access (a software package) to develop this application. We used the Microsoft Excel to verify the accurate execution of the dose formula. The manual and computer time using this program required for calculating the RPH dose were compared. The developed application calculates RPH dose for pediatric patients based on European Association of Nuclear Medicine dose card, weight based, body surface area based, Clark, Solomon Fried, Young and Webster's formula. It is password protected to prevent the accidental damage and stores the complete record of patients that can be exported to Excel sheet for further analysis. It reduces the burden of calculation and saves considerable time i.e., 2 min computer time as compared with 102 min (manual calculation with the calculator for all seven formulas for 25 patients). The software detailed above appears to be an easy and useful method for calculation of pediatric RPH dose in routine clinical practice. This software application will help in helping the user to routinely applied ALARA principle while pediatric dose administration.

  9. Development of dopamine receptor radiopharmaceuticals for the study of neurological and psychiatric disorders

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Jogeshwar Mukherjee

    2009-01-02

    Our goals in this grant application are directed towards the development of radiotracers that may allow the study of the high-affinity state (functional state) of the dopamine receptors. There have been numerous reports on the presence of two inter-convertible states of these (G-protein coupled) receptors in vitro. However, there is no report that establishes the presence of these separate affinity states in vivo. We have made efforts in this direction in order to provide such direct in vivo evidence about the presence of the high affinity state. This understanding of the functional state of the receptors is of critical significance in our overall diagnosis and treatment of diseases that implicate the G-protein coupled receptors. Four specific aims have been listed in the grant application: (1). Design and syntheses of agonists (2). Radiosyntheses of agonists (3). In vitro pharmacology of agonists (4). In vivo distribution and pharmacology of labeled derivatives. We have accomplished the syntheses and radiosyntheses of three agonist radiotracers labeled with carbon-11. In vitro and in vivo pharmacological experiments have been accomplished in rats and preliminary PET studies in non-human primates have been carried out. Various accomplishments during the funded years, briefly outlined in this document, have been disseminated by several publications in various journals and presentations in national and international meetings (Society of Nuclear Medicine, Society for Neuroscience and International Symposium on Radiopharmaceutical Chemistry).

  10. Technetium-99m based small molecule radiopharmaceuticals and radiotracers targeting inflammation and infection.

    Science.gov (United States)

    Kniess, Torsten; Laube, Markus; Wüst, Frank; Pietzsch, Jens

    2017-10-31

    In nuclear medicine, the detection of inflamed and infected lesions is of growing interest. Extensive efforts have been made to develop radiopharmaceuticals specific for inflammation or for discriminating sterile inflammation from infection. (99m)Tc is the worldwide most widely used radioisotope for SPECT imaging. The scope of this review article is to give an overview on the development of (99m)Tc-labelled small molecule radiotracers targeting inflammatory lesions and infections, ranging from their radiopharmacological evaluation to examples of their clinical applications. A systematic overview of (99m)Tc-citrate, (99m)Tc-antibiotics and antifungal agents as well as (99m)Tc-labelled antimicrobial peptides is provided. Additionally, the class of (99m)Tc-labelled cyclooxygenase-2 inhibitors is discussed, since cyclooxygenases are known to play a key role in inflammatory diseases and also in malignant neoplastic diseases. In a short perspective, newer developments in the field of inflammation imaging covering (99m)Tc-labelled bacteriophages and chemotactic peptides are highlighted.

  11. In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals.

    Science.gov (United States)

    Pinto, Suyene Rocha; Sarcinelle, Michelle Alvares; de Souza Albernaz, Marta; da Silva, Franciana Maria Rosa; Seabra, Sergio Henrique; Almeida do Nascimento, Patricia; Carvalho, Cosme Leonardo Gomes; Santos-Oliveira, Ralph

    2014-10-01

    The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Technetium-99m complex of N-(2-pyridylmethyl)iminodiacetic acid as a new renal radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Karube, Yoshiharu; Iwamoto, Koji; Takata, Jiro [Fukuoka Univ. (Japan). Faculty of Pharmaceutical Sciences

    1999-04-01

    A tetradentate chelating agent constituting of an iminodiacetic acid group and a nitrogen atom of pyridine, N-(2-pyridylmethyl)iminodiacetic acid (PMIDA), was coordinated with {sup 99m}Tc and evaluated as a renal functional agent. The complex of PMIDA with {sup 99m}Tc was prepared by using a stannous chloride solution as a reducing agent. The chelating efficiency was analyzed by thin layer chromatography and electrophoresis. Chelation with {sup 99m}Tc resulted in a single radiochemical product. Biological studies were performed in mice and rats. {sup 99m}Tc-PMIDA was removed from the circulation solely by the kidneys. Clearance of {sup 99m}Tc-PMIDA from the blood and the kidneys was as rapid as that of {sup 99m}Tc-diethylenetriaminepentaacetic acid. The rate of blood clearance was unaffected by the administration of probenecid (a test for tubular secretion by the weak-acid mechanism), so that the glomerular filtration rate could be estimated by measuring its clearance from the blood. The results in animals with myohemoglobinuric acute renal failure suggested that {sup 99m}Tc-PMIDA might be a useful renal function radiopharmaceutical. (author)

  13. Biodistribution of the radiopharmaceutical technetium-99m-sodium phytate in rats after splenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Kercia Regina Santos Gomes; Acucena, Maria Kadja Meneses Torres; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Cirurgia]. E-mail: aldo@ufrnet.br

    2008-12-15

    Drugs and surgery can interfere with the biodistribution of radiopharmaceuticals and data about the effect of splenectomy on the metabolism of phytate-Tc-99m are scarce. This study aimed at evaluating the interference of splenectomy on phytate-Tc-99m biodistribution and liver function in rats. The SP group rats (n=6) underwent splenectomy. In group C (control) the animals were not operated on. After 15 days, all rats were injected with 0.1 mL of Tc-99m-phytate via orbital plexus (0.66 MBq). After 30 minutes, liver samples were harvested, weighed and the percentage of radioactivity per gram (%ATI/g) was determined by a Wizard Perkin-Elme gamma counter. The ATI%/g in splenectomized rats (0.99{+-}0.02) was significantly higher than in controls (0.4{+-}0.02), (p=0.034). ALT, AST and HDL were significantly lower in SP rats (p= 0.001) and leucocytosis was observed in SP rats. In conclusion, splenectomy in rats changed the hepatic biodistribution of Tc-99m-phytate and liver enzymatic activity. (author)

  14. New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents.

    Science.gov (United States)

    Brink, Alice; Helliwell, John R

    2017-05-01

    Multiple possibilities for the coordination of fac -[Re(CO) 3 (H 2 O) 3 ] + to a protein have been determined and include binding to Asp, Glu, Arg and His amino-acid residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro. The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals. The core experimental concept involved the use of state-of-art tuneable synchrotron radiation at the Diamond Light Source to optimize the rhenium anomalous dispersion signal to a large value ( f '' of 12.1 electrons) at its L I absorption edge with a selected X-ray wavelength of 0.9763 Å. At the Cu  K α X-ray wavelength (1.5418 Å) the f '' for rhenium is 5.9 electrons. The expected peak-height increase owing to the optimization of the Re f '' was therefore 2.1. This X-ray wavelength tuning methodology thereby showed the lower occupancy rhenium binding sites as well as the occupancies of the higher occupancy rhenium binding sites.

  15. New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents

    Directory of Open Access Journals (Sweden)

    Alice Brink

    2017-05-01

    Full Text Available Multiple possibilities for the coordination of fac-[Re(CO3(H2O3]+ to a protein have been determined and include binding to Asp, Glu, Arg and His amino-acid residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro. The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals. The core experimental concept involved the use of state-of-art tuneable synchrotron radiation at the Diamond Light Source to optimize the rhenium anomalous dispersion signal to a large value (f′′ of 12.1 electrons at its LI absorption edge with a selected X-ray wavelength of 0.9763 Å. At the Cu Kα X-ray wavelength (1.5418 Å the f′′ for rhenium is 5.9 electrons. The expected peak-height increase owing to the optimization of the Re f′′ was therefore 2.1. This X-ray wavelength tuning methodology thereby showed the lower occupancy rhenium binding sites as well as the occupancies of the higher occupancy rhenium binding sites.

  16. Development of anti β glucan aptamers for use as radiopharmaceutical in the identification of fungal Infections

    Energy Technology Data Exchange (ETDEWEB)

    Lacerda, Camila Maria de Sousa; Reis, Mariana Flister; Correa, Cristiane Rodrigues; Andrade, Antero S.R., E-mail: cmsl@cdtn.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEM-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    Invasive fungal infections caused by Candida albicans, are recognized as a major cause of morbidity and mortality in immuno compromised individuals. Patients may not show obvious clinical signs or symptoms, making it difficult to detect its origin or new focus that developed through hematogenous spread. Nuclear medicine could contribute to an early diagnosis of fungal infections, since specific markers are available. The aim of this study was to develop, through SELEX technique (Systematic Evolution of Ligands by Exponential Enrichment), aptamers for beta glucan for subsequent labeling with {sup 99}mTc and evaluation of this radiopharmaceutical in the diagnosis of invasive fungal infections, scintigraphy. To obtain aptamers were performed 15 cycles of SELEX technique, using centrifugation as separation method of oligonuclotideos linked to the beta-glucan is not connected. The DNA bands were observed in all 15 cycles. The oligonucleotides obtained after cycles were cloned using the standard protocol kit-Topo TA vector (Invitrogen), and subjected to sequencing Megabase. Three aptamers for yeast cells were selected for this study. Further, other studies should be performed to assess the specificity and affinity thereof for later use in the diagnosis of fungal infections. (author)

  17. PET/CT WITH 68Ga-PSMA IN PROSTATE CANCER: RADIOPHARMACEUTICAL BACKGROUND AND CLINICAL IMPLICATIONS.

    Science.gov (United States)

    Giovacchini, Giampiero; Giovannini, Elisabetta; Riondato, Mattia; Ciarmiello, Andrea

    2017-11-01

    In the last twenty years, positron emission tomography / computed tomography (PET/CT) with radiolabeled choline, represented the most powerful imaging modality for prostate cancer (PCa). However, the low positive detection rate of the technique for PSA PET/CT predicts PCa-specific survival, have not yet been investigated. Numerous clinical studies have been published, some of them with histopathological verification so that despite the recent introduction in the clinical field reliable estimation of sensitivity and specificity of 68Ga-PSMA PET/CT have been obtained through meta-analyses. Most clinical studies with PET/CT with 68Ga-PSMA are retrospective, single-institutional studies and in many cases include heterogeneous patient cohorts. Thus, multidisciplinary, well-throughout prospective trials are needed to better define the clinical implications of 68Ga-PSMA PET/CT in PCa patients. The increasing availability of positron emission tomography / magnetic resonance (PET/MR) hybrid devices promotes the use of this radiopharmaceutical especially at initial staging when identification of tumor localization and of extra-prostatic disease represent clinically relevant questions. PSMA cold ligands can also be labeled with beta emitters with good chemical stability so that 68Ga-PSMA PET/CT can be used to guide radiometabolic therapy of advanced metastatic PCa patients through 177Lu-labeled PSMA ligands. `. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Evaluation of sup 3 H-paroxetine as a radiopharmaceutical for lung function

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kenji; Goromaru, Tsuyoshi (Fukuyama Univ., Hiroshima (Japan). Faculty of Pharmacy and Pharmaceutical Sciences)

    1989-07-01

    The potential of {sup 3}H-paroxetine as a radiotracer for in vivo study of the function in mouse lung was examined. The high accumulation of radioactivity in the mouse lung was observed after intravenous administration of {sup 3}H-paroxetine. However, the distributions of radioactivity in the mouse lung were not significantly decreased by treatment with paroxetine or other monoamine uptake inhibitors (6-nitroquipazine, desipramine and GBR 12909). It was found that the radioactivity in the mouse lung at 1 hr after intravenous administration of {sup 3}H-paroxetine was due to unmetabolized {sup 3}H-paroxetine from TLC and HPLC analyses. Furthermore, {sup 3}H-paroxetine exhibits both saturable and high affinity binding sites in mouse lung with a maximal number of binding sites (B{sub max}) of 303 fmoles/mg protein and a dissociation constant (K{sub d}) of 92.2 pM. These results suggest that {sup 3}H-paroxetine would be a suitable radiopharmaceutical for in vivo study of the function of lung as a metabolic organ of serotonin.

  19. Calculation of the Dose of Samarium-153-Ethylene Diamine Tetramethylene Phosphonate (153Sm-EDTMP as a Radiopharmaceutical for Pain Relief of bone Metastasis

    Directory of Open Access Journals (Sweden)

    Fatemeh Razghandi

    2016-04-01

    Full Text Available Introduction One of the important applications of nuclear physics in medicine is the use of radioactive elements as radiopharmaceuticals. Metastatic bone disease is the most common form of malignant bone tumors. Samarium-153-ethylene diamine tetramethylene phosphonate (153Sm-EDTMP as a radiopharmaceutical is used for pain palliation. This radiopharmaceutical usually emits beta particles, which have a high uptake in bone tissues. The purpose of this study was to calculate the radiation dose distribution of 153Sm-EDTMP in bone and other tissues, using MCNPX Monte Carlo code in the particle transport model. Materials and Methods Dose delivery to the bone was simulated by seeking radiopharmaceuticals on the bone surface. The phantom model had a simple cylindrical geometry and included bone, bone marrow, and soft tissue. Results The simulation results showed that a significant amount of radiation dose was delivered to the bone by the use of this radiopharmaceutical. Conclusion Thebone acted as a fine protective shield against rays for the bone marrow. Therefore, the trivial absorbed dose by the bone marrow caused less damage to bone-making cells. Also, the high absorbed dose of the bone could destroy cancer cells and relieve the pain in the bone.

  20. Influence of radiation on endotoxin test using the PTS TM for 18-FDG radiopharmaceutical

    Directory of Open Access Journals (Sweden)

    Ralph Santos-Oliveira

    2010-09-01

    Full Text Available F-18 FDG (2-[18-F] fluoro-2-deoxy-D-glucose is the most frequently used radiopharmaceutical for PET and PET CT imaging exams. The FDA recently approved the use of the PTS TM (Portable Test System as an alternative to the standard test proposed by the United States Pharmacopeia using the LAL (Limulus Amebocyte Lysates, that takes longer to perform (about 1h than the PTS TM (15 min. Recent studies have demonstrated that radiation could interfere with the PTS TM test. In order to study the effects of radiation on the PTS TM test and/or equipment, 27 batches of F-18 FDG produced in the Nuclear Engineering Institute were analyzed. The results showed that no direct correlation with radiation was found in any of the cases.O FDG-18 é o radiofármaco mais utilizado nos exames de PET e PET CT. O FDA recentemente aprovou o uso do PTS TM (Portable Test System como método alternativo ao teste padrão de endotoxina, proposto pela Farmacopéia Americana, considerando que no primeiro há um tempo de espera de 1 hora frente a somente 15 minutos do segundo. Estudo recentes demonstram que a radiação poderia interferir no teste do PTS TM. De modo a avaliar os efeitos da radiação no teste PTS TM foram analisados 27 lotes de F-18 FDG produzidos no Instituto de Engenharia Nuclear. Os resultados demonstraram que em todos os casos nenhuma correlação direta com a radiação foi observada.

  1. Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons.

    Science.gov (United States)

    Boschi, Alessandra; Martini, Petra; Pasquali, Micol; Uccelli, Licia

    2017-09-01

    99mTc is the most commonly used radionuclide in the field of diagnostic imaging, a noninvasive method intended to diagnose a disease, assess the disease state and monitor the effects of treatments. Annually, the use of 99mTc, covers about 85% of nuclear medicine applications. This isotope releases gamma rays at about the same wavelength as conventional X-ray diagnostic equipment, and owing to its short half-life (t½ = 6 h) is ideal for diagnostic nuclear imaging. A patient can be injected with a small amount of 99mTc and within 24 h almost 94% of the injected radionuclide would have decayed and left the body, limiting the patient's radiation exposure. 99mTc is usually supplied to hospitals through a 99Mo/99mTc radionuclide generator system where it is produced from the β decay of the parent nuclide 99Mo (t½ = 66 h), which is produced in nuclear reactors via neutron fission. Recently, the interruption of the global supply chain of reactor-produced 99Mo, has forced the scientific community to investigate alternative production routes for 99mTc. One solution was to consider cyclotron-based methods as potential replacement of reactor-based technology and the nuclear reaction 100Mo(p,2n)99mTc emerged as the most worthwhile approach. This review reports some achievements about 99mTc produced by medical cyclotrons. In particular, the available technologies for target design, the most efficient extraction and separation procedure developed for the purification of 99mTc from the irradiated targets, the preparation of high purity 99mTc radiopharmaceuticals and the first clinical studies carried out with cyclotron produced 99mTc are described.

  2. Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats

    Energy Technology Data Exchange (ETDEWEB)

    Holanda, Cecilia Maria de Carvalho Xavier [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Lab. de Radiobiologia Experimental e Ensaios Antiparasitarios; Barbosa, Delianne Azevedo; Demeda, Vanessa Favero; Bandeira, Flora Tamires Moura [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Escola de Medicina; Medeiros, Hilkea Carla Souza de; Pereira, Kercia Regina Santos Gomes [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Programa de Pos-Graduacao em Bioquimica; Barbosa, Vanessa Santos de Arruda [Universidade Federal de Campina Grande (UFCG), PB (Brazil); Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Nucleo de Cirurgia Experimental

    2014-03-01

    Purpose: to evaluate the effect of hydroalcoholic extract of A. muricata on biodistribution of two radiopharmaceuticals: sodium phytate and dimercaptosuccinic acid (DMSA), both labeled with {sup 99m}technetium. Methods: twenty four Wistar rats were divided into two treated groups and two controls groups. The controls received water and the treated received 25mg/kg/day of A. muricata by gavage for ten days. One hour after the last dose, the first treated group received {sup 99m}Tc-DMSA and the second sodium {sup 99m}Tc-phytate (0.66MBq each group), both via orbital plexus. Controls followed the same protocol. Forty min later, all groups were sacrificed and the blood, kidney and bladder were isolated from the first treated group and the blood, spleen and liver isolated from the second treated group. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated using a gamma counter. Results: the statistical analysis showed that there was a statistically significant decrease (p<0.05) in the uptake of %ATI/g in bladder (0.11±0.01and1.60±0.08), kidney (3.52±0.51and11.84±1.57) and blood (0.15±0.01and 0.54±0.05) between the treated group and control group, respectively. Conclusion: the A. muricata hydroalcoholic extract negatively influenced the uptake of {sup 99m}Tc-DMSA in bladder, kidney and blood of rats (author)

  3. [11C] Methionine as PET radiopharmaceutical produced at CDTN/CNEN

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina B.; Ferreira, Soraya Z.; Carvalho, Tiago F.; Silva, Juliana B. da, E-mail: mbs@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos

    2013-07-01

    Carbon-11 ({sup 11}C) is an attractive radionuclide used in positron emission tomography (PET) since carbon is a ubiquitous element in biomolecules. Positron emitter-labeled amino acids are being widely used as indicators of tumor activity due to enhanced expression of amino acid transporter systems in cancer cells. L-[Methyl-({sup 11}C)] Methionine or [{sup 11}C]Methionine is being used in neuro-oncology and, unlike 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ({sup 18}FDG), gives more contrast images and improves brain tumor diagnosis. The aim of this work was to develop the synthesis and quality control of [{sup 11}C]Methionine at the Radiopharmaceuticals Research and Production Facility (UPPR) of CDTN/CNEN. The synthesis of [{sup 11}C] Methionine was performed using two Sep-Pak tC18 plus cartridges one as solid support for the {sup 11}C-methylation of the precursor L-homocysteine thiolactone hydrochloride and another for purification. The pH, radionuclidic identity and purity, residual solvents, radiochemical and chemical purity of the final product were evaluated as described on the European Pharmacopoeia 7.0 monograph. Total synthesis time was 18 minutes, the radiochemical yield was approximately 15% (non-decay corrected) and radiochemical purity was greater than 95%. [{sup 11}C]Methionine was successfully synthesized at CDTN using the described procedures and complied with quality requirements. Due to the rapid growth of oncologic PET scans in last decade, {sup 11}C labelling holds great promises in the next few years with the application of other tracers beyond {sup 18}FDG. This pioneering work of UPPR/CDTN represents a response to the demands of a growing nuclear medicine in the country focused on achieving better diagnostic imaging. (author)

  4. Tenth report on survey of the adverse reaction to radiopharmaceuticals. The 13th survey in 1987

    Energy Technology Data Exchange (ETDEWEB)

    1989-04-01

    The 13th questionnaire survey was performed for adverse reaction to radiopharmaceuticals occuring during one year from April 1987 through March 1988. A questionnaire was sent to 1,063 facilities. Seven hundred and sixty-nine replies (72%) were received. Twenty-one cases of adverse reaction and 11 cases of drug defect were reported from 23 facilities (3.0%), giving annual incidences of 2.4 and 1.3, respectively, per 100,000 administrations. The ratio of the 1987's incidence to the 1986's incidence was 0.78 for adverse reaction and 0.96 for drug defect. The incidence of adverse reaction decreased from 0.0060-0.0061% during the period between 1983 and 1984 to 0.0037-0.0045% during the period between 1985 and 1987. The incidence of adverse reaction was highest for I-131 Adosterol (191/100,000), followed by Tc-99m DTPA (14/100,000), I-131 Hippuran (13/100,000), Tc-99m DMSA (7/100,000), pyrophosphate for labeling red blood cells (6/100,000), Tc-99m MAA (4/100,000), Tc-99m HMDP (1/100,000), and Ga-67 citrate (0.8/100,000). Adverse reactions included: reactions to the vagus nerves (n=9), allergic reaction (n=8), and others, including dyspnea and vomiting (n=4). Drug defects occurred in 6 cases of Tc-99m MDP, 2 cases of Tc-99m HMDP, one case of Tc-99m MAA, one case of Tc-99m DTPA, and one case of I-131 sodium iodinate capsule. (Namekawa, K).

  5. Cu(II) bis(thiosemicarbazone) radiopharmaceutical binding to serum albumin: further definition of species dependence and associated substituent effects

    Energy Technology Data Exchange (ETDEWEB)

    Basken, Nathan E. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States); Green, Mark A. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: magreen@purdue.edu

    2009-07-15

    Introduction: The pyruvaldehyde bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and diacetyl bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-ATSM) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) radiopharmaceutical appears to exhibit only nonspecific binding to HSA and animal serum albumins. Methods: To further probe the structural basis for the species dependence of this albumin binding interaction, we examined protein binding of these three radiopharmaceuticals in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat and elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Results: Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. Conclusions: The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate.

  6. Garantia da qualidade aplicada à produção de radiofármacos Quality assurance in radiopharmaceutical production

    Directory of Open Access Journals (Sweden)

    Elaine Bortoleti de Araújo

    2008-03-01

    Full Text Available Radiofármacos são produzidos e distribuídos no Brasil há mais de 40 anos pelos Institutos da Comissão Nacional de Energia Nuclear (CNEN, particularmente o Instituto de Pesquisas Energéticas e Nucleares (IPEN, para uso em procedimentos diagnósticos e terapêuticos em Medicina Nuclear. Alguns aspectos da produção, distribuição e utilização dos radiofármacos são bastante particulares, diferenciando-se dos fármacos convencionais, tornando necessário estabelecer regulamentação específica para tais produtos. Neste sentido, existem orientações da Organização Mundial de Saúde (OMS bem como regulamentações de órgãos sanitários de diversos países que já fazem distinção aos radiofármacos nas legislações específicas.Radiopharmaceuticals have been produced and distributed in Brazil for almost 40 years, by the Institutes of the Comissão Nacional de Energia Nuclear (CNEN particularly the Instituto de Pesquisas Energéticas e Nucleares (IPEN, and applied in Nuclear Medicine in diagnostic and therapeutic procedures. Some aspects related to the production, distribution and use of radiopharmaceuticals are very uncommon and different from the conventional drugs, making necessary the introduction of an specific regulation for these radioactive drugs. In this way, the World Health Organization (WHO and health regulatory agencies from different countries have specific legislations to radiopharmaceuticals production and use.

  7. 177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

    Directory of Open Access Journals (Sweden)

    Héctor Mendoza-Nava

    2016-01-01

    Full Text Available 177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4-folate-bombesin with gold nanoparticles (AuNPs in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs and gastrin-releasing peptide receptors (GRPRs overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys1Lys3(DOTA-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS, particle size distribution (DLS, TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%. Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%. 177Lu-dendrimer(AuNP-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

  8. Radiolabeling of Ceftriaxone with 99mTc as a Targeting Radiopharmaceutical for Staphylococcus Aureus Detection in Mouse Model

    Directory of Open Access Journals (Sweden)

    Akram Fazli

    2012-03-01

    Full Text Available Introduction Bacterial infection is one of the major causes of morbidity and mortality especially in developing countries. Nuclear medicine has an important role in helping the diagnosis of deep-seated infections by developing more specific radiopharmaceuticals. The aim of this study was to evaluate 99mTc-labeling ceftriaxone as a new radiopharmaceutical for Staphylococcus aureus infection imaging in nuclear medicine. Materials and Methods Radiolabeling of ceftriaxone was carried out by adding 370 MBq of 99mTc to 10 mg of ceftriaxone in the presence of 50 µg of SnCl2.2H2O at pH=5. The radiochemical purity and stability tests at room temperature and human blood serum were evaluated with ITLC. Intramuscular infection was induced by injection of Staphylococcus aureus into the left thigh muscle of the mice. The biodistribution of 99mTc-ceftriaxone was studied in normal and infected mice at various times post-injection. Results Radiochemical purity of the product was 94.5±5.4% with a good stability at room temperature and human serum, 80.6% and 71.2% after 24 h, respectively. The biodistribution studies showed the localization of 99mTc-ceftriaxone at the site of infection with high sensitivity without any significant accumulation in vital organs. Conclusion Due to the ease of 99mTc-ceftriaxone conjugation method, high labeling efficiency, and high uptake in the infected muscle, it may provide a promising candidate as a targeting radiopharmaceutical for imaging infectious foci due to Staphylococcus aureus in nuclear medicine.

  9. Quality control of PET radiopharmaceuticals by high-performance liquid chromatography with tris(2,2'-bipyridyl)ruthenium(II) electrogenerated chemiluminescence detection.

    Science.gov (United States)

    Nakao, Ryuji; Furutsuka, Kenji; Fukumura, Toshimitsu; Yamaguchi, Masatoshi; Suzuki, Kazutoshi

    2010-02-01

    A highly sensitive reversed-phase liquid chromatographic (HPLC) method was investigated to analyze a range of positron emission tomography (PET) radiopharmaceuticals using electrogenerated chemiluminescence (ECL) detection. ECL is based on the reaction of PET molecules with tris(2,2'-bipyridyl)ruthenium(III) [Ru(bpy)(3)(3+)], which is generated through the on-line electro-oxidation of Ru(bpy)(3)(2+). In 21 different radiopharmaceuticals studied, 18 compounds could be detected with detection limits (signal-to-noise ratio = 3) of 0.12-72 ng/mL per 20 microL injection. Sufficient reproducibility and linearity were obtained for the quantitative determination of PET molecules in pharmaceutical fluid. This method could be successfully applied to quality control tests of PET radiopharmaceuticals with ultra-high specific radioactivity. (c) 2009 John Wiley & Sons, Ltd.

  10. Preclinical assessment of dopaminergic system in rats by MicroPET using three positron-emitting radiopharmaceuticals

    Science.gov (United States)

    Lara-Camacho, V. M.; Ávila-García, M. C.; Ávila-Rodríguez, M. A.

    2014-11-01

    Different diseases associated with dysfunction of dopaminergic system such as Parkinson, Alzheimer, and Schizophrenia are being widely studied with positron emission tomography (PET) which is a noninvasive method useful to assess the stage of these illnesses. In our facility we have recently implemented the production of [11C ]-DTBZ, [11C ]-RAC, and [18F ]-FDOPA, which are among the most common PET radiopharmaceuticals used in neurology applications to get information about the dopamine pathways. In this study two healthy rats were imaged with each of those radiotracers in order to confirm selective striatum uptake as a proof of principle before to release them for human use.

  11. The effect of giving detailed information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information.

    Science.gov (United States)

    Kaya, Eser; Ciftci, Ismail; Demirel, Reha; Cigerci, Yeliz; Gecici, Omer

    2010-02-01

    Nuclear medicine procedures use radiopharmaceuticals, which produce radiation and potential adverse reactions, albeit at a low rate. It is the patient's ethical, legal, and medical right to be informed of the potential side effects of procedures applied to them. Our purpose was to determine the effect of providing information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information. This study was completed in two separate Nuclear Medicine Departments. The study included 620 (247 M, 373 F) patients who had been referred for myocardial perfusion, bone, dynamic renal, and thyroid scintigraphic examinations. The patients were divided into two groups according to whether they requested more information or not. Group 1 consisted of 388 patients who wanted to receive more information about the procedure, while Group 2 consisted of 232 patients who did not request additional information. The State-Trait Anxiety Inventory (STAI-S and STAI-T) was used to determine a patient's anxiety level. After simple information was given, state and trait anxiety levels were measured in both groups. We gave detailed information to the patients in Group 1 and then measured state anxiety again. Detailed information included an explanation of the radiopharmaceutical risk and probable side effects due to the scan procedure. There was no statistical difference between Groups 1 and 2 in STAI-T or STAI-S scores after simple information was given (p = 0.741 and p = 0.945, respectively). The mean value of STAI-S score was increased after the provision of detailed information and there was a statistically significant difference between after simple information SATI-S and after detailed information STAI-S (p information, while there was no change in 32 patients. After detailed information, the greatest increase in STAI-S score was seen in the myocardial perfusion scan patients, when evaluating according to scan procedure (p Informed consent

  12. Preclinical assessment of dopaminergic system in rats by MicroPET using three positron-emitting radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Lara-Camacho, V. M., E-mail: victormlc13@hotmail.com; Ávila-García, M. C., E-mail: victormlc13@hotmail.com; Ávila-Rodríguez, M. A., E-mail: victormlc13@hotmail.com [Unidad PET, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510, México, D.F. (Mexico)

    2014-11-07

    Different diseases associated with dysfunction of dopaminergic system such as Parkinson, Alzheimer, and Schizophrenia are being widely studied with positron emission tomography (PET) which is a noninvasive method useful to assess the stage of these illnesses. In our facility we have recently implemented the production of [{sup 11}C]-DTBZ, [{sup 11}C]-RAC, and [{sup 18}F]-FDOPA, which are among the most common PET radiopharmaceuticals used in neurology applications to get information about the dopamine pathways. In this study two healthy rats were imaged with each of those radiotracers in order to confirm selective striatum uptake as a proof of principle before to release them for human use.

  13. A restricted access material for rapid analysis of [(11)C]-labeled radiopharmaceuticals and their metabolites in plasma

    DEFF Research Database (Denmark)

    Gillings, N.

    2009-01-01

    INTRODUCTION: Analysis of the radioactive components in plasma taken during positron emission tomography (PET) measurements is often vital for the correct quantification of the PET data. The described high-performance liquid chromatography (HPLC) method has been developed to provide a fast......, sensitive and robust method for the measurement of plasma samples from PET studies using [(11)C]-labeled radiopharmaceuticals. METHODS: Unadulterated plasma samples were analyzed directly, following a simple filtration, by the use of a small extraction column, containing a restricted access material...

  14. Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: a concise overview and practical guidance for a risk-based approach.

    Science.gov (United States)

    Lange, Rogier; ter Heine, Rob; Decristoforo, Clemens; Peñuelas, Iván; Elsinga, Philip H; van der Westerlaken, Monique M L; Hendrikse, N Harry

    2015-05-01

    Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations are not always adequate for their production. Strict compliance may have a huge resource impact, without further improving product quality. In this paper we give an overview of the applicable legislation and guidelines and propose a risk-based approach for their implementation. We focus on a few controversial Good Manufacturing Practice topics: cleanroom classification, air pressure regime, cleanroom qualification and microbiological monitoring. We have developed an algorithm to assess the combined risk of microbiological contamination of a radiopharmaceutical preparation process and propose corresponding Good Manufacturing Practice classification levels. In our opinion, the risk of carry-over of radiopharmaceuticals by individuals cannot be contained by pressure differences, and complicated regimes with underpressured rooms are not necessary in most situations. We propose a sterility assurance level of 10 for radiopharmaceuticals that are administered within a working day, irrespective of their use. We suggest the adoption of limits for environmental monitoring of microbial contamination, as proposed by Bruel and colleagues, on behalf of the French Society of Radiopharmacy. Recently launched regulatory documents seem to breathe a more liberal spirit than current legislation and recognize the need for the use of risk assessment. We argue that future legislation be further harmonized and state risk assessment as the gold standard for implementation of drug quality regulations for the preparation of unlicensed radiopharmaceuticals.

  15. Harvard--MIT research program in short-lived radiopharmaceuticals. Progress report, September 1, 1977--April 30, 1978. [/sup 99m/Tc, positron-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.; Brownell, G.L.

    1978-05-01

    Progress is reported on the following studies: chemistry studies designed to achieve a more complete understanding of the fundamental chemistry of technetium in order to facilitate the design of future radiopharmaceuticals incorporating the radionuclide /sup 99m/Tc; the development of new radiopharmaceuticals intended to improve image quality and lower radiation doses by the use of short-lived radionuclides and disease-specific agents; the development of short-lived positron-emitting radionuclides which offer advantages in transverse section imaging of regional physiological processes; and studies of the toxic effects of particulate radiation.

  16. Limulus amebocyte lysate testing: adapting it for determination of bacterial endotoxin in 99mTc-labeled radiopharmaceuticals at a hospital radiopharmacy.

    Science.gov (United States)

    Mitra, Arpit; Joshi, Sangeeta; Arjun, Chanda; Kulkarni, Savita; Rajan, Ramakrishna

    2014-12-01

    A bacterial endotoxin test (BET) is required to detect or quantify bacterial endotoxin that may be present in radiopharmaceutical preparations. The test uses Limulus amebocyte lysate, which, in the presence of bacterial endotoxin and divalent calcium ions, causes the formation of a coagulin gel. (99m)Tc-labeled radiopharmaceuticals have chelating ligands such as diethylene triamine pentaacetic acid (DTPA), ethylene dicysteine (EC), L,L-ethyl cysteinate dimer (ECD), N-[2,4,6-trimethyl-3 bromoacetanilid] iminodiacetic acid (mebrofenin), dimercapto succinic acid-III (DMSA-III), dimercapto succinic acid-V (DMSA-V), and several others, which form a coordination complex with Na-(99m)Tc-O4 in the presence of reducing agents. During BET by the gel-clot method, the free sulfhydryl (-SH) and carboxyl (-COOH) in some of the chelating agents in the final (99m)Tc-labeled radiopharmaceuticals decrease the free divalent calcium ion concentration, which in turn inhibits coagulin gel formation. This study was designed using the premise that addition of calcium chloride solution to the reaction mixture would nullify this effect. We present here the data obtained from BET assay analysis of (99m)Tc-labeled radiopharmaceuticals and the cold kits from which they are made (EC, ECD, methoxyisobutylisonitrile, DTPA, mebrofenin, methylene diphosphonic acid [MDP], DMSA-III, and DMSA-V) using 2 different dilutions, maximum valid dilution (MVD) and half maximum valid dilution (MVD/2), with and without the addition of calcium chloride at a final concentration of 300 μM. It was observed that at MVD and MVD/2 all of the (99m)Tc-labeled kits exhibited interference in coagulin gel formation with the exception of (99m)Tc-methoxyisobutylisonitrile, (99m)Tc-MDP, (99m)Tc-mebrofenin, and (99m)Tc-ECD. However, only the cold kits of methoxyisobutylisonitrile and MDP did not show inhibition. An addition of calcium chloride solution nullified this interference at both MVD and MVD/2 in all of the (99m

  17. Radiolabeling of trastuzumab with {sup 177}Lu via DOTA, a new radiopharmaceutical for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)], E-mail: hrajabi@modares.ac.ir; Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Salouti, Mojtaba [Department of Biology, School of Sciences, Islamic Azad University - Zanjan Branch, Zanjan (Iran, Islamic Republic of)

    2009-05-15

    Aim: Trastuzumab is a monoclonal antibody that is used in treating breast cancer. We labeled this monoclonal antibody with lutetium-177 and performed in vitro quality control tests as a first step in the production of a new radiopharmaceutical. Material and Methods: Trastuzumab was labeled with lutetium-177 using DOTA as chelator. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Immunoreactivity and toxicity of the complex were tested on MCF7 breast cancer cell line. Results: The radiochemical purity of the complex was 96{+-}0.9%. The stabilities in phosphate buffer and in human blood serum at 96 h postpreparation were 93{+-}1.2% and 85{+-}3.5%, respectively. The immunoreactivity of the complex was 89{+-}1.4%. At a concentration of 1 nM, the complex killed 70{+-}3% of MCF7 cells. At 1.9 nM, 90{+-}5% of the cells were killed. Conclusions: The results showed that the new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy against breast cancer.

  18. Radiopharmaceutical management in Brazil: the case of fluorodeoxyglucose production; Gestao de radiofarmacos no Brasil: o caso da producao de fluordesoxiglicose

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Vitor da Silva

    2016-07-01

    Nowadays, the combination of fluorodeoxyglucose tracer (FDG) and PET/CT equipment is the best technological condition for medical diagnosis, allowing the generation of images that associate anatomy and metabolic functions of tissues or organs. Constitutional Amendment (CA) No 49 of 2006, relaxed the state monopoly on the production of radioactive substances, allowing private investment in radioisotope area with half-life of less than or equal to two hours, as a way to increase the supply of these materials to national health sector. In order to reflect on the Brazilian production of radiopharmaceuticals, especially FDG was performed a theoretical study with a qualitative approach, substantiated by documentary research and data collection through a questionnaire sent to the producing private companies of this radiopharmaceutical. Initially, it sought to identify in the federal level the legal and regulatory parameters for the activity; then the existing competitive environment was observed, and, finally, were prospected the business perspectives on the behavior of domestic demand of this product. The results showed the growth of production and its largest geographical distribution in the country, beyond what would be possible only considering public investment; but short of expectations surrounding the enactment of Constitutional Amendment. Private entrepreneurs believe in market growth; since, most of the population has no access to the benefits that the medical imaging diagnostic with the use of FDG may allow. It was also noted that there is a need to improve the regulatory framework in relation to licensing procedures; as well as implementation of common marketing parameters. (author)

  19. The nineteenth report on survey of the adverse reaction to radiopharmaceuticals. The 22nd survey in 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    The report included cases of adverse reaction to radiopharmaceuticals and of drug defect which had occurred from April 1, 1996 to March 31, 1997. The survey was done by the questionnaire to 1,182 nuclear medicine facilities in Japan and 961 answers (81.3%) were obtained. Thirty one cases of adverse reactions were reported from 31 facilities in 1,264,865 cases to that radiopharmaceuticals had been administered and 7 cases of drug defect were reported from 7 facilities. Adverse reactions involved 8 vasovagal reactions, 14 allergic reactions and 9 others for {sup 99m}Tc-MAA (adverse reaction rate in %: 0.0025), -PYP (0.0352), -HM-PAO (0.0025), -MDP{center_dot}HMDP (0.0008), -DTPA (0.0189), -HSA (0.0086), -MIBI (0.0066), -tetrofosmin (0.0032), -MAG{sub 3} (0.0147), {sup 201}Tl-TlCl2 (0.0014), {sup 123}I-NaI capsule (0.0068), -IMP (0.0016), {sup 131}I-NaI capsule (0.0128) and -iodomethyl-norcholesterol (0.2752). Drug defects involved 1 incomplete radio-labeling, 3 broken or contaminated vials and 3 others. Relative to those hitherto, adverse reaction cases tended to be decreasing and drug defect cases clearly decreased. (K.H.)

  20. Effects of the variation of samples geometry on radionuclide calibrator response for radiopharmaceuticals used in nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Albuquerque, Antonio Morais de Sa; Fragoso, Maria Conceicao de Farias; Oliveira, Mercia L. [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    In the nuclear medicine practice, the accurate knowledge of the activity of radiopharmaceuticals which will be administered to the subjects is an important factor to ensure the success of diagnosis or therapy. The instrument used for this purpose is the radionuclide calibrator. The radiopharmaceuticals are usually contained on glass vials or syringes. However, the radionuclide calibrators response is sensitive to the measurement geometry. In addition, the calibration factors supplied by manufactures are valid only for single sample geometry. To minimize the uncertainty associated with the activity measurements, it is important to use the appropriate corrections factors for the each radionuclide in the specific geometry in which the measurement is to be made. The aims of this work were to evaluate the behavior of radionuclide calibrators varying the geometry of radioactive sources and to determine experimentally the correction factors for different volumes and containers types commonly used in nuclear medicine practice. The measurements were made in two ionization chambers of different manufacturers (Capintec and Biodex), using four radionuclides with different photon energies: {sup 18}F, {sup 99m}Tc, {sup 131}I and {sup 201}Tl. The results confirm the significant dependence of radionuclide calibrators reading on the sample geometry, showing the need of use correction factors in order to minimize the errors which affect the activity measurements. (author)

  1. Manufacturing and test of a low cost polypropylene bag to reduce the radioactive gas released by a radiopharmaceutical production facility

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, Jose Carlos Freitas; Lacerda, Marco Aurelio de Sousa, E-mail: jcft@cdtn.b, E-mail: masl@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (SEPRA/ CDTN/CNEN-MG) Belo Horizonte, MG (Brazil). Servico de Protecao Radiologica; Nascimento, Leonardo Tafas Constantino do; Silva, Juliana Batista da, E-mail: ltcn@cdtn.b, E-mail: silvajb@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (SECPRA/ CDTN/CNEN-MG) Belo Horizonte, MG (Brazil). Secao de Producao de Radiofarmacos

    2011-07-01

    The main objective of this work was to evaluate the efficiency of a plastic gas storage bag to reduce the radioactive gas released by the chimney of a radiopharmaceutical production facility during the 2-[{sup 18}F]fluoro-2- deoxy-D-glucose ({sup 18}FDG) synthesis. The studied facility was the Development Centre of Nuclear Technology (CDTN/CNEN) in Belo Horizonte, Brazil. The bag was manufactured utilizing foils of polypropylene of 360 x 550 x 0.16 mm and disposable components of the cassette of the synthesizer. Two synthesis of {sup 18}FDG were done using the same hot cell and synthesizer to evaluate the efficiency of the bag. The manufactured bag was put in the gas exit of the synthesizer and the activity reported by the online radiation monitoring system in the first synthesis. These results were compared to the activity released in a synthesis performed without the bag. We observed when the bag was used the amount released was about 0.2% in 270 minutes. The second synthesis was performed without the bag, about 7,1% of the input activity was released by the exhaust of the facility in the same time interval. The bag presented a very good efficiency in the reducing of the radioactive gas released by the chimney of the radiopharmaceutical production facility. (author)

  2. The eleventh report on survey of the adverse reaction to radiopharmaceuticals; The 14th survey in 1988

    Energy Technology Data Exchange (ETDEWEB)

    1991-03-01

    This report deals with adverse reactions to radiopharmaceuticals occurring during the period from April 1, 1988 through March 31, 1989. Qestionnaires were sent to 1,110 facilities, and 748 (67.4%) responded. Twenty one cases of adverse reactions and 13 cases of drug defect were reported from a total of 24 facilities (3.2%), giving an annual occurrence of 2.6 cases and 1.6 cases, respectively, for 100,000 examinations. The incidence of adverse reactions was the highest for I-131-6{beta}-iodomethyl-19-norcholesterol (n=254), followed by I-131 sodium iodide capsule (n=29), Tc-99m PMT injection (n=16), Tc-99m DTPA (n=12), I-131 sodium iodohippurate (n=12), Tc-99m pertechnetate (n=3), Tc-99m MDP injection (n=2), Tc-99m phytate (n=2), and Ga-67 citrate injection(n=one). Adverse reactions included reactions to the vagus nerves (n=7), allergic reactions (n=3), and others (n=11). Radiopharmaceuticals reported as drug defects were as follows: Tc-99m HMDP, Tc-99m MDP, Tc-99m PMT, Tc-99m pyrophosphate, and Tc-99m generator. (N.K.).

  3. The fifteenth report on survey of the adverse reaction to radiopharmaceuticals; The 18th survey in 1992

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    This report deals with adverse reactions to radiopharmaceuticals occurring during the period from April 1, 1992 through March 31, 1993. Questionnaires were sent to 1,160 facilities, and 894 (77.1%) responded. Fifteen cases of adverse reactions and 8 cases of drug defects were reported from a total of 19 facilities (2.1%), giving an annual occurrence of 1.4 cases of adverse reactions and 0.8 cases of drug defects for 100,000 examinations. The incidence of adverse reactions was the highest for sodium iodohippurate injection (I-123 or I-131)(n=5), followed by Tc-99m DTPA injection (n=3), Ga-67 citrate injection (n=2), Tc-99m RBC pyrophosphate (n=2), I-131 iodomethyl norcholesterol (n=one), Tc-99m macroaggregated albumin(MAA) (n=one), and Tc-99m Sn colloid (n=one). Adverse reactions included reactions to vagus nerves (n=5), allergic reactions (n=5) and others (n=5). Radiopharmaceuticals reported as drug defects were as follows: Tc-99m generator, Tc-99m MAA, Tc-99m pyrophosphorie acid, Tc-99m hydroxymethylene diphosphonate(HMDP), Tc-99m methylene diphosphonate(MDP), Tc-99m hexamethylpropyleneamine oxime(HMPAO), and Ga-67 citrate. (N.K.).

  4. The thirteenth report on survey of the adverse reaction to radiopharmaceuticals; The 16th survey in 1990

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    This report deals with adverse reactions to radiopharmaceuticals occurring during the period from April 1, 1990 through March 31, 1991. Questionnaires were sent to 1,141 facilities, and 857 (75.1%) responded. Thirteen cases of adverse reactions and 15 cases of drug defects were reported from a total of 23 facilities (2.7%), giving an annual occurrence of 1.3 cases and 1.5 cases, respectively, for 100,000 examinations. Among the reported 13 adverse reactions, the highest incidence was seen for both I-131 sodium iodohippurate (n=4) injection and Tc-99m DTPA injection (n=4), followed by I-131 iodomethyl norcholesterol (n=2). Each one of the other adverse reactions was seen for Tc-99m RBC injection, Tc-99m HMDP injection, and I-123 IMP injection. Adverse reactions included reactions to the vagus nerves (n=8), allergic reactions (n=2), and others (n=3). Drug defects consisted of unfavorable distribution (n=8), destroyed or contaminated containers (n=4), unfavorable elution (n=2), and mixed foreign bodies (n=one). Radiopharmaceuticals reported as drug defects were as follows: Ga-67 citrate, Tc-99m generator, Tc-99m MAA, Tc-99m RBC, Tc-99m DMSA, Tc-99m MDP, Tc-99m HMDP, Xe-133 injection, and Tl-201 chloride. (N.K.).

  5. Selection of aptamers for use as radiopharmaceuticals in bacterial infection diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Ieda Mendes; Faria, Ligia Santana de; Correa, Cristiane Rodrigues; Andrade, Antero Silva Ribeiro de, E-mail: imendesf@yahoo.com.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    The difficulty in early detection of specific foci in the bacterial infection caused by bacteria has raised the need to search for new techniques for this purpose, since these foci require prolonged treatment with antibiotics and in some cases even drainage or, if applicable, removal of prostheses or grafts. Detection of bacterial infections by scintigraphy has the advantage that an image of the whole body could be obtained. This study aims to obtain aptamers specific bacteria for future use as radiopharmaceutical. The SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology can generate oligonucleotides (aptamers) that are able to bind with high affinity and specificity to a specific target, from small molecules to complex proteins, by using rounds of enrichment and amplification. Aptamers can be labeled with different radionucleotides such as {sup 99m}Tc, {sup 18}F and {sup 32}P. In this study aptamers anti-peptidoglycan, the main component of the outer cell wall of bacteria, were obtained through SELEX. The SELEX started with a pool of ssDNA that had 10{sup 15}different sequences (library), each oligo has two fixed regions merging a portion of 25 random nucleotides. Initially, the library of ssDNA was incubated with peptidoglycan, for 1h at 37 dec C with stirring. Subsequently, amplification of oligonucleotides that were able to bind to peptidoglycan was performed by PCR (Polymerase Chain Reaction). The amplified oligonucleotides were again incubated with peptidoglycan, amplified and purified. At the end of 15 rounds of selection the oligonucleotides were cloned using TOPO plasmid and Escherichia coli strain Top10F'. The plasmid DNA from 40 colonies were extracted and quantified. The plasmids were sequenced using the sequencing MegaBase, and two different aptamers sequences were obtained from all clones. The aptamers obtained were synthesized and subsequently labeled with {sup 32}P in the 5' end. The labeled aptamers were incubated

  6. Macrocyclic chelator-coupled gastrin-based radiopharmaceuticals for targeting of gastrin receptor-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Good, Stephan; Wang, Xuejuan; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Walter, Martin A.; Mueller-Brand, Jan [University Hospital, Institute of Nuclear Medicine, Basel (Switzerland); Waser, Beatrice; Reubi, Jean-Claude [University of Berne, Department of Pathology, Bern (Switzerland); Behe, Martin P. [Philipps-University of Marburg, Department of Nuclear Medicine, Marburg (Germany)

    2008-10-15

    Diethylenetriamine-pentaacetic acid (DTPA)-coupled minigastrins are unsuitable for therapeutic application with the available {beta}-emitting radiometals due to low complex stability. Low tumour-to-kidney ratio of the known radiopharmaceuticals is further limiting their potency. We used macrocyclic chelators for coupling to increase complex stability, modified the peptide sequence to enhance radiolytic stability and studied tumour-to-kidney ratio and metabolic stability using {sup 111}In-labelled derivatives. Gastrin derivatives with decreasing numbers of glutamic acids were synthesised using {sup 111}In as surrogate for therapeutic radiometals for in vitro and in vivo studies. Gastrin receptor affinities of the {sup nat}In-metallated compounds were determined by receptor autoradiography using {sup 125}I-CCK as radioligand. Internalisation was evaluated in AR4-2J cells. Enzymatic stability was determined by incubating the {sup 111}In-labelled peptides in human serum. Biodistribution was performed in AR4-2J-bearing Lewis rats. IC{sub 50} values of the {sup nat}In-metallated gastrin derivatives vary between 1.2 and 4.8 nmol/L for all methionine-containing derivatives. Replacement of methionine by norleucine, isoleucine, methionine-sulfoxide and methionine-sulfone resulted in significant decrease of receptor affinity (IC{sub 50} between 9.9 and 1,195 nmol/L). All cholecystokinin receptor affinities were >100 nmol/L. All {sup 111}In-labelled radiopeptides showed receptor-specific internalisation. Serum mean-life times varied between 2.0 and 72.6 h, positively correlating with the number of Glu residues. All {sup 111}In-labelled macrocyclic chelator conjugates showed higher tumour-to-kidney ratios after 24 h (0.37-0.99) compared to {sup 111}In-DTPA-minigastrin 0(0.05). Tumour wash out between 4 and 24 h was low. Imaging studies confirmed receptor-specific blocking of the tumour uptake. Reducing the number of glutamates increased tumour-to-kidney ratio but resulted in

  7. SU-C-204-03: DFT Calculations of the Stability of DOTA-Based-Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Khabibullin, A.R.; Woods, L.M. [University of South Florida, Tampa, Florida (United States); Karolak, A.; Budzevich, M.M.; Martinez, M.V. [H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); McLaughlin, M.L.; Morse, D.L. [University of South Florida, Tampa, Florida (United States); H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)

    2016-06-15

    Purpose: Application of the density function theory (DFT) to investigate the structural stability of complexes applied in cancer therapy consisting of the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated to Ac225, Fr221, At217, Bi213, and Gd68 radio-nuclei. Methods: The possibility to deliver a toxic payload directly to tumor cells is a highly desirable aim in targeted alpha particle therapy. The estimation of bond stability between radioactive atoms and the DOTA chelating agent is the key element in understanding the foundations of this delivery process. Thus, we adapted the Vienna Ab-initio Simulation Package (VASP) with the projector-augmented wave method and a plane-wave basis set in order to study the stability and electronic properties of DOTA ligand chelated to radioactive isotopes. In order to count for the relativistic effect of radioactive isotopes we included Spin-Orbit Coupling (SOC) in the DFT calculations. Five DOTA complex structures were represented as unit cells, each containing 58 atoms. The energy optimization was performed for all structures prior to calculations of electronic properties. Binding energies, electron localization functions as well as bond lengths between atoms were estimated. Results: Calculated binding energies for DOTA-radioactive atom systems were −17.792, −5.784, −8.872, −13.305, −18.467 eV for Ac, Fr, At, Bi and Gd complexes respectively. The displacements of isotopes in DOTA cages were estimated from the variations in bond lengths, which were within 2.32–3.75 angstroms. The detailed representation of chemical bonding in all complexes was obtained with the Electron Localization Function (ELF). Conclusion: DOTA-Gd, DOTA-Ac and DOTA-Bi were the most stable structures in the group. Inclusion of SOC had a significant role in the improvement of DFT calculation accuracy for heavy radioactive atoms. Our approach is found to be proper for the investigation of structures with DOTA-based-radiopharmaceuticals

  8. In vitro kinetic studies on the mechanism of oxygen-dependent cellular uptake of copper radiopharmaceuticals

    Science.gov (United States)

    Holland, Jason P.; Giansiracusa, Jeffrey H.; Bell, Stephen G.; Wong, Luet-Lok; Dilworth, Jonathan R.

    2009-04-01

    The development of hypoxia-selective radiopharmaceuticals for use as therapeutic and/or imaging agents is of vital importance for both early identification and treatment of cancer and in the design of new drugs. Radiotracers based on copper for use in positron emission tomography have received great attention due to the successful application of copper(II) bis(thiosemicarbazonato) complexes, such as [60/62/64Cu(II)ATSM] and [60/62/64Cu(II)PTSM], as markers for tumour hypoxia and blood perfusion, respectively. Recent work has led to the proposal of a revised mechanism of hypoxia-selective cellular uptake and retention of [Cu(II)ATSM]. The work presented here describes non-steady-state kinetic simulations in which the reported pO2-dependent in vitro cellular uptake and retention of [64Cu(II)ATSM] in EMT6 murine carcinoma cells has been modelled by using the revised mechanistic scheme. Non-steady-state (NSS) kinetic analysis reveals that the model is in very good agreement with the reported experimental data with a root-mean-squared error of less than 6% between the simulated and experimental cellular uptake profiles. Estimated rate constants are derived for the cellular uptake and washout (k1 = 9.8 ± 0.59 × 10-4 s-1 and k2 = 2.9 ± 0.17 × 10-3 s-1), intracellular reduction (k3 = 5.2 ± 0.31 × 10-2 s-1), reoxidation (k4 = 2.2 ± 0.13 mol-1 dm3 s-1) and proton-mediated ligand dissociation (k5 = 9.0 ± 0.54 × 10-5 s-1). Previous mechanisms focused on the reduction and reoxidation steps. However, the data suggest that the origins of hypoxia-selective retention may reside with the stability of the copper(I) anion with respect to protonation and ligand dissociation. In vitro kinetic studies using the nicotimamide adenine dinucleotide (NADH)-dependent ferredoxin reductase enzyme PuR isolated from the bacterium Rhodopseudomonas palustris have also been conducted. NADH turnover frequencies are found to be dependent on the structure of the ligand and the results confirm

  9. In vitro radio autographic studies of the biodistribution of radiopharmaceuticals on blood elements

    Energy Technology Data Exchange (ETDEWEB)

    Eipoll-Hamer, E.; De Paula, E.F. [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil). Centro de Pesquisa Basica; Freitas, L.C. [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil). Servico de Quimioterapia; Pereira, M.J.S.; Carvalho, J.J.; Porto, L.C.M.S. [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Dept. de Histologia e Embriologi; Fonseca, L.M. [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear; Gutfilen, B.; Bernardo Filho, M. [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biofisica e Biometria

    1998-02-01

    In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na{sup 99m} Tc O{sub 4}), methylene-diphosphonic acid ({sup 99m} Tc-M D P) and glucoheptonate acid ({sup 99m} Tc-G H A) to blood elements using centrifugation and radio autographic techniques. Heparinized blood was incubated with the labelled compounds for 0,1,2,3,4, 6 and 24 h. Plasma (P) and blood cells (B C) were isolated and precipitated with 5% trichloroacetic acid (TCA), and soluble (S F) and insoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with Lm-1 radio autographic emulsions and percent radioactivity (%rad) in P and B C was determined. The binding of Na{sup 99m} Tc O{sub 4} (5 rad) to P was 61.2 (0 h) and 46.0% (24 h), and radioautography showed 63.7% (0 h) and 43.3% (24 h). The binding to B C was 38.8% (0 h) and 54.0% (24 h), and radioautography showed 36.3% (0 h) and 56.7% (24 h). {sup 99m} Tc-M D P study presented 91.1% (0 h) to P and 87.2%(24 h), and radioautography showed presented 91.1% (0 h) to P and 87.2% (24 h), and radioautography showed 67.9% (0 h) and 67.4% (24 h). The binding to B C was 8.9% (0 h) and 12.8% (24 h), and radioautography showed 32.1% (0 h) and 32.6% (24 h). {sup 99m} Tc-G H A study was 90.1% (0 h) to P and 79.9% (24 h), and radioautography showed 67.2% (0 h) and 60.1% (24 h). The binding to B C was 9.9% (0 h) and 20.1% (24 h), and radioautography showed 32.8% (0 h) and 39.9% (24 h). The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) is qualitatively in accordance. (author) 20 refs., 2 tabs.

  10. Biokinetics and dosimetry of target-specific radiopharmaceuticals for molecular imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Torres G, E. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Gonzalez V, A. [UAEM, Facultad de Medicina, Toluca (Mexico); Murphy, C.A. de [INCMNSZ, Mexico D.F. (Mexico)

    2006-07-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. {sup 99m}Tc-HYNlC-TOC has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. Therapies using radiolabeled anti-CD20 have demonstrated their efficacy in patients with B-cell non Hodgkin's Iymphoma (NHL). The aim of this study was to establish biokinetic models for {sup 99m}Tc-HYNlC-TOC and {sup 188}Re-anti-CD20 prepared from Iyophilized kits, and to evaluate their dosimetry as target-specific radiopharmaceuticals. Whole-body images were acquired at different times after {sup 99m}Tc-HYNlC-TOC or {sup 188}Re-anti-CD20 administration obtained from instant freeze-dried kit formulations with radiochemical purities > 95 %. Regions of interest (ROls) were drawn around source organs on each time frame. The cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate time-activity curves in each organ, to adjust the biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. {sup 99m}Tc-HYNlC-TOC images showed an average tumor/blood (heart) ratio of 4.3 {+-} 0.7 in receptor-positive tumors at 1 h and the mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv. Results showed that after administration of 7 GBq of {sup 188}Re-anti-CD20 the absorbed dose to whole body would be 0.7 Gy (0.1 mGy/MBq) which is the indicated dose for non Hodgkin's Iymphome therapies. (Author)

  11. In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements

    Directory of Open Access Journals (Sweden)

    Ripoll-Hamer E.

    1998-01-01

    Full Text Available In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99mTcO4, methylenediphosphonic acid (99mTc-MDP and glucoheptonate acid (99mTc-GHA to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P and blood cells (BC were isolated and precipitated with 5% trichloroacetic acid (TCA, and soluble (SF and insoluble fractions (IF were separated. Blood samples were prepared (0 and 24 h and coated with LM-1 radioautographic emulsions and percent radioactivity (%rad in P and BC was determined. The binding of Na 99mTcO4 (%rad to P was 61.2% (0 h and 46.0% (24 h, and radioautography showed 63.7% (0 h and 43.3% (24 h. The binding to BC was 38.8% (0 h and 54.0% (24 h, and radioautography showed 36.3% (0 h and 56.7% (24 h. 99mTc-MDP study presented 91.1% (0 h to P and 87.2% (24 h, and radioautography showed 67.9% (0 h and 67.4% (24 h. The binding to BC was 8.9% (0 h and 12.8% (24 h, and radioautography showed 32.1% (0 h and 32.6% (24 h. 99mTc-GHA study was 90.1% (0 h to P and 79.9% (24 h, and radioautography showed 67.2% (0 h and 60.1% (24 h. The binding to BC was 9.9% (0 h and 20.1% (24 h, and radioautography showed 32.8% (0 h and 39.9% (24 h. The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation is qualitatively in accordance

  12. Positron emitting nuclides and their synthetic incorporation in radiopharmaceuticals. [Labeled with /sup 11/C, /sup 13/N, and /sup 18/F

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.

    1976-01-01

    /sup 11/C, /sup 13/N, and /sup 15/O has potential applicability to the study of metabolism in humans. Problems in the synthesis of radiopharmaceuticals labeled with /sup 11/C, /sup 13/N, and /sup 18/F are described: quality control, radiation exposure, carboxylic acids, glucose, amines, amino acids, nitrosources, fluoroethanol. 54 references. (DLC)

  13. Drug composition matters : The influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP

    NARCIS (Netherlands)

    Lange, R.; de Klerk, J. M H; Bloemendal, H. J.|info:eu-repo/dai/nl/269266178; Ramakers, R. M.; Beekman, F. J.|info:eu-repo/dai/nl/107730200; van der Westerlaken, M. M L; Hendrikse, N. H.; ter Heine, R.

    2015-01-01

    Introduction: 188Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for

  14. Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP

    NARCIS (Netherlands)

    Lange, R.; Klerk, J.M. de; Bloemendal, H.J.; Ramakers, R.M.; Beekman, F.J.; Westerlaken, M.M. van der; Hendrikse, N.H.; Heine, R. ter

    2015-01-01

    INTRODUCTION: (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for

  15. Determination of Sn in 99{sup m}Tc Radiopharmaceutical Kits by Polarographic Methods; Determinacion de Estano en Radiofarmacos de 99{sup m}Tc mediante Metodos Polarograficos

    Energy Technology Data Exchange (ETDEWEB)

    Castro, M.; Cruz, J.; Sanchez, M.

    2009-07-01

    Kits of 99{sup m}Tc radiopharmaceuticals are used in nuclear medicine for diagnosis of different diseases. Sn (II) is one of the essential components in their formulations, which is used for reduction 99{sup m}Tc-pertechnetate in cold kits for on-site preparation 99{sup m}Tc-pertechnetate radiopharmaceuticals. Usually, these cold kits contain different additives (complexing agents, antioxidants, buffers, etc.) and the amount of Sn (II) varies from kit to kit. The determination of Sn in these products is essential in assessing their quality. We report here the development of a new polarographic method for the determination of Sn (II) and total Sn in representative radiopharmaceuticals kits (for the content of Sn and chemical composition) produced at the Center of Isotopes of Cuba (CENTIS). These methods were validated by analysis of variance and recovery techniques. From the results of the validation, the characteristic functions of uncertainties and fits are considered for the established methods, which give the necessary evidences to demonstrate the usefulness of these methods according to the current trends in Analytical Chemistry. This work provides practical results of great importance for CENTIS. After the speciation of Sn in the MAG3 radiopharmaceuticals kit is inferred that the production process is affected by uncontrolled factors that influence in the product stability, which demonstrates the necessity for analytical tools for the characterization of products and processes. (Author) 57 refs.

  16. Metal-ion Speciation in Blood Plasma as a Tool in Predicting the "in vivo" Behaviour of Potential Bone-Seeking Radiopharmaceuticals

    NARCIS (Netherlands)

    Zeevaart, J.R.

    2001-01-01

    In a quest for more effective radiopharmaceuticals for palliation of pain experienced by metastatic bone cancer patients, results obtained with the therapeutic radionuclides 153 SM, 166 Ho and 117mSn complexed to bone-seeking phopsphate ligands are related. As phosphonates are known to enhance the

  17. Dosimetric aspects of the treatment of metastatic bone pain with radiopharmaceuticals; Aspectos dosimetricos de los tratamientos del dolor oseo metastasico con radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, T.; Marti, J. F.; Olivas, C.; Vercher, J. L.; Repetto, R.; Bello, P.

    2014-02-01

    Within the context of treatment of metastatic bone pain with bone seeking radiopharmaceuticals, this paper expounds the results of an analysis of available molecules (both approved for clinical use or still under study) intended to obtain a detailed comparison of their dosimetric characteristics. These can be used to supplement the list of already know differences between them, such as efficacy, appearance and length of the palliative effect, eventual tumoricidal effect, myelotoxicity, sale price and availability. Seven radiopharmaceuticals have been analysed, five of them are based on beta emission radionuclides: {sup 3}2P, {sup 1}53Sm, {sup 1}86Re and {sup 1}88Re and the other two ones are based on high Linear energy Transference emission radionuclides: {sup 1}17mSn and {sup 2}23Ra a series of estimates of the main dosimetric parameters for each radiopharmaceutical analysed have been obtained. The values obtained might be worth being incorporated to the risk/benefit analysis that precedes every choice of the specific radiopharmaceutical to be used with an individual patient. In this way, we hope these results will be of some help for those Nuclear Medicine specialists interested in the treatment of oncological bone pathologies. (Author)

  18. Focal accumulation of a radiopharmaceutical in the liver on technetium-99m gated blood pool and Apcitide scintigraphy leading to the diagnosis of superior vena cava obstruction.

    Science.gov (United States)

    Sherman, Paul M; Bridwell, Robert S

    2002-01-01

    Focal increased enhancement or radiopharmaceutical uptake in the liver has been associated with superior vena cava syndrome. This report describes the finding in a patient imaged with a relatively new agent, Tc-99m Apcitide. The collateral pathways responsible for the liver "hot spot" are reviewed, as is the role of Tc-99m Apcitide in deep venous thrombosis imaging.

  19. APPLICATION OF LIQUID-CHROMATOGRAPHY COMBINED WITH MASS-SPECTROMETRY (LC-MS) TO ESTABLISH IDENTITY AND PURITY OF PET-RADIOPHARMACEUTICALS

    NARCIS (Netherlands)

    FRANSSEN, EJF; LUURTSEMA, G; MEDEMA, J; VISSER, GM; JERONISMUSSHALINGH, CM; BRUINS, AP; VAALBURG, W

    This article describes the application of liquid chromatography combined with mass-spectrometry (LC-MS) as a new quality control tool for PET-radiopharmaceuticals. The final step in the production of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18-FDG) is a purification by HPLC. This procedure was validated

  20. Studies of technetium-99m nitridobisdithiocarboxylate leucocyte specific radiopharmaceutical: [{sup 99m}TcN(DTCX){sub 2}], DTCX=CH{sub 3}(CH{sub 2}){sub 8}CS{sub 2}. the cellular and subcellular distribution in human blood cells, and chemical behaviour. synthesis of the analogous rhenium-188 radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Demaimay, Florian; Roucoux, Alain E-mail: Alain.Roucoux@ensc-rennes.fr; Dazord, Leontine; Noiret, Nicolas; Moisan, Annick; Patin, Henri

    1999-02-01

    The distribution of the radiopharmaceutical ([{sup 99m}TcN(DTCX){sub 2}], DTCX=CH{sub 3}(CH{sub 2}){sub 8}CS{sub 2}) in the leucocyte population determinated by a density separation with double gradient Polymorphprep{sup TM} was studied. Microautoradiographic analysis showed a subcellular distribution of the radiomarker in human blood cells. This technique confirmed the observed lymphocyte selectivity (69%) and revealed that the uptake was predominantly cytoplasmic around the nucleus. A labeling mechanism by passive endocytosis could be proposed involving a required lipophilicity of the radiopharmaceutical for lymphocyte targeting. Finally, we describe the new synthesis with an efficient yield and radiochemical purity of the analogous radiopharmaceutical [{sup 188}ReN(DTCX){sub 2}].

  1. Biodistribution of the radiopharmaceutical technetium-99m-sodium phytate in rats after splenectomy

    Directory of Open Access Journals (Sweden)

    Kércia Regina Santos Gomes Pereira

    2008-12-01

    Full Text Available Drugs and surgery can interfere with the biodistribution of radiopharmaceuticals and data about the effect of splenectomy on the metabolism of phytate-Tc-99m are scarce. This study aimed at evaluating the interference of splenectomy on phytate-Tc-99m biodistribution and liver function in rats. The SP group rats (n=6 underwent splenectomy. In group C (control the animals were not operated on. After 15 days, all rats were injected with 0.1mL of Tc-99m-phytate via orbital plexus (0.66MBq. After 30 minutes, liver samples were harvested, weighed and the percentage of radioactivity per gram (%ATI/g was determined by a Wizard Perkin-Elme gama counter. The ATI%/g in splenectomized rats (0.99±0.02 was significantly higher than in controls (0.4±0.02, (p=0.034. ALT, AST and HDL were significantly lower in SP rats (p= 0.001 and leukocytosis was observed in SP rats. In conclusion, splenectomy in rats changed the hepatic biodistribution of Tc-99m-phytate and liver enzimatic activity.O radiofármaco fitato-Tc-99m é usado no diagnóstico através de exames de imagem, na dependência de sua biodistribuição. O objetivo do trabalho foi avaliar efeito da esplenectomia na biodistribuição do fitato-Tc-99m e função hepática em ratos Wistar. Sob anestesia e técnica asséptica, os animais do grupo SP (n=6 foram esplenectomizados. Grupo C(controle; n=6 não operado. Após 15 dias, injeção de 0,1ml de fitato-Tc-99m via plexo orbital (0,66MBq. Após 30 minutos, retiradas biópsias hepáticas para determinação do percentual de radioatividade/grama (% ATI/g, usando-se contador gama WizardPerkin-Elmer®. Realizada dosagem de ALT, AST e HDL, e leucometria. Estatística pelo teste t, significância 0,05. O %ATI/g nos ratos esplenectomizados foi 0,99 ± 0,2 e nos controles 0,40 ± 0,2 (p=0,034. ALT, AST e HDL tiveram dosagens significativamente menores nos esplenectomizados (p=0,01, com leucocitose, comparando com controles. Em conclusão, em ratos a esplenectomia

  2. Evaluation of different detection systems to determine the radiochemical purity of the technetium eluate and the radiopharmaceutical sestamibi

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Poliane Angelo de L.; Andrade, Wellington G., E-mail: polianeangelo@gmail.com, E-mail: wandrade@cnen.gov.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Santos, Luiz Antonio P.; Lima, Fabiana Farias de, E-mail: luanps@uol.com.br, E-mail: fflima@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN/CNEN-PE), Recife, PE (Brazil)

    2013-07-01

    Since 2008 the Brazilian Health Surveillance Agency (ANVISA) has imposed some rules requiring that Nuclear Medicine Services (NMS) perform a minimum of tests with the radiopharmaceuticals before they are administered to their patients according to the Resolution n. 38 (RDC 38). Among the tests, the radiochemical purity is very important because the effectiveness for the use in vivo, and the fact radiochemical impurities may increase the radiation dose beyond to cause some damage in the diagnostic images. Radiochemical Purity is determined by ascendant chromatography technique and when it is used by NMS, the strips are analyzed in dose calibrator. Furthermore, the low activity on the strips can produce errors due to the low detection of this equipment type. Therefore, the aim of this paper is to compare different methods for determining the radiochemical purity of {sup 99m}Tc eluate and {sup 99m}Tc-MIBI radiopharmaceutical; gamma camera, and dose calibrator. The study was developed in three clinics in Recife-PE, and 15 analyses were performed to determine radiochemical purity of technetium eluate and {sup 99m}Tc-MIBI. For evaluating technetium eluate it was used Whatman® 3MM paper in 1cmx8cm strips. On the other hand, for analyzing MIBI radiopharmaceutical it was used 3 Whatman® 3MM paper strips and 3 with silica gel in 1cmx6.5cm format. According to the manufactures, an 1cm point from the base of the strip was labeled. It was dropped 50μ1 of sodium pertechnetate and {sup 99m}Tc-MIBI and, then, the strips were put in the glass tank, with solvent, according to the pharmacopoeia and inserts of the drug manufacturers. After the solvent front reached the end point, the strips were removed and allowed to dry. Firstly, the radioactivity count was made with a gamma camera. After that, the strips were cut in half (eluate) and in 2.5 cm from the base (MIBI) and measured with a dose calibrator. The results of the average radiochemical purity of the eluate in clinics A, B

  3. Evaluation of kidney function in dogs suffering from canine encephalitozoonosis by standard clinical pathological and radiopharmaceutical techniques.

    Science.gov (United States)

    Botha, W S; Dormehl, I C; Goosen, D J

    1986-06-01

    Canine encephalitozoonosis can be responsible for a severe renal disease in dogs which may develop into progressive, irreversible kidney failure. Three pure-bred Boxer littermates with confirmed encephalitozoonosis were subjected to sequential clinical pathological tests and renal biopsies. The endogenous serum creatinine and urea levels showed an initial temporary reduction but later increased steadily. The phenolsulphonphthalein retention test confirmed this end-stage renal disease. Initial hyper-gamma globulinaemia showed a rapid decline. Urinalysis was an indicator of chronic renal disease and the kidney biopsies confirmed progressive irreversible kidney lesions. Evaluation of sequential tests are advocated for the setting of a prognosis. The radiopharmaceutical techniques employed proved to be sensitive indicators of renal dysfunction and a means of evaluating the function of the left and right kidney separately.

  4. Interactive radiopharmaceutical facility between Yale Medical Center and Brookhaven National Laboratory. Progress report, October 1976-June 1979

    Energy Technology Data Exchange (ETDEWEB)

    Gottschalk, A.

    1979-01-01

    DOE Contract No. EY-76-S-02-4078 was started in October 1976 to set up an investigative radiochemical facility at the Yale Medical Center which would bridge the gap between current investigation with radionuclides at the Yale School of Medicine and the facilities in the Chemistry Department at the Brookhaven National Laboratory. To facilitate these goals, Dr. Mathew L. Thakur was recruited who joined the Yale University faculty in March of 1977. This report briefly summarizes our research accomplishments through the end of June 1979. These can be broadly classified into three categories: (1) research using indium-111 labelled cellular blood components; (2) development of new radiopharmaceuticals; and (3) interaction with Dr. Alfred Wolf and colleagues in the Chemistry Department of Brookhaven National Laboratory.

  5. Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats.

    Science.gov (United States)

    Rocha, G S; Pereira, M O; Benarroz, M O; Frydman, J N G; Rocha, V C; Pereira, M J; Fonseca, A S; Medeiros, A C; Bernardo-Filho, M

    2011-01-01

    Effects of sucralose sweetener on blood constituents labelled with technetium-99m ((99m)Tc) on red blood cell (RBC) morphology, sodium pertechnetate (Na(99m)TcO(4)) and diethylenetriaminepentaacetic acid labeled with (99m)Tc ((99m)Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood constituents from Wistar rats was undertaken for determining the activity percentage (%ATI) on blood constituents. RBC morphology was also evaluated. Na(99m)TcO(4) and (99m)Tc-DTPA biodistribution was used to determine %ATI/g in organs. There was no alteration on RBC blood constituents and morphology %ATI. Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in different organs. These findings are associated to the sucralose sweetener in specific organs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, G.S.; Pereira, M.O. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Universidade Federal do Rio Grande do Norte, Programa de Pos-Graduacao em Ciencias da Saude, Avenida General Gustavo Cordeiro de Farias, s/n, 59010180 Natal, Rio Grande do Norte (Brazil); Benarroz, M.O.; Frydman, J.N.G.; Rocha, V.C. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Pereira, M.J. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Fisiologia, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Fonseca, A.S., E-mail: adnfonseca@ig.com.b [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Universidade Federal do Estado do Rio de Janeiro, Instituto Biomedico, Departamento de Ciencias Fisiologicas, Rua Frei Caneca, 94, Rio de Janeiro 20211040 (Brazil); Medeiros, A.C. [Universidade Federal do Rio Grande do Norte, Programa de Pos-Graduacao em Ciencias da Saude, Avenida General Gustavo Cordeiro de Farias, s/n, 59010180 Natal, Rio Grande do Norte (Brazil); Bernardo-Filho, M. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Instituto Nacional do Cancer, Coordenadoria de Pesquisa Basica, Praca Cruz Vermelha, 23, 20230130 Rio de Janeiro (Brazil)

    2011-01-15

    Effects of sucralose sweetener on blood constituents labelled with technetium-99m ({sup 99m}Tc) on red blood cell (RBC) morphology, sodium pertechnetate (Na{sup 99m}TcO{sub 4}) and diethylenetriaminepentaacetic acid labeled with {sup 99m}Tc ({sup 99m}Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood constituents from Wistar rats was undertaken for determining the activity percentage (%ATI) on blood constituents. RBC morphology was also evaluated. Na{sup 99m}TcO{sub 4} and {sup 99m}Tc-DTPA biodistribution was used to determine %ATI/g in organs. There was no alteration on RBC blood constituents and morphology %ATI. Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in different organs. These findings are associated to the sucralose sweetener in specific organs.

  7. Evaluation of different counting methods for use in radiochemical purity testing procedures for 99mTc-labelled radiopharmaceuticals.

    Science.gov (United States)

    Maioli, Claudio; Bestetti, Alberto; Milani, Franco; Cornalba, Gian Paolo; Tagliabue, Luca; Di Benedetto, Domenica; Rognoni, Ilaria; Luigi Tarolo, Gian; Paroni, Rita

    2008-04-01

    The efficiency and accuracy of different methods for quality control of radiopharmaceutical preparations for diagnostic purpose were studied. The radiochemical purity of (99m)Tc Tetrafosmin, (99m)Tc Exametazime, (99m)Tc Sestamibi and (99m)Tc Oxidronate was evaluated by different thin layer chromatography systems, followed by cutting of the strips into two or three sections and by the measurement of radioactivity distribution by dose calibrator or gamma counter. In addition, to confirm the accuracy of these routine procedures, the strips were cut into a number of micro-sections (14-25) and each of them evaluated by the gamma counter. The three tested procedures gave similar results and revealed a good and comparable accuracy. The radioactivity measurement with the dose calibrator remains the most practicable because of the rapidity of execution.

  8. The 24th report on survey of the adverse reaction to radiopharmaceuticals (The 27th survey in 2001)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-02-01

    The survey in the title involves occasions of adverse reactions and drug defects of radiopharmaceuticals and its twenty seventh one in 2001 (April 1, 2001-March 31, 2002) is reported herein. The survey was conducted by questionnaire to 1,210 facilities, of which 1,048 (86.6%) answered. Adverse reaction (32 cases/1,390,843=0.0019% occasion) and drug defect (5, 0.0004%) were reported from 27 facilities: They were 0.0017-0.0025% and 0.0001-0.0005%, respectively, after 1997. Frequent occasion of adverse reaction was seen in {sup 131}I-methyl-norcholesterol (0.1704%) and in {sup 131}I-sodium hippurate (0.1020%). The former was considered to be due to the ingredient, ethanol. Occasion of the adverse reaction of other drugs was less than 0.1%. The drug defects were due to the abnormal distribution (4 cases) and formulation defect (1). (N.I.)

  9. A novel, self-shielded modular radiosynthesis system for fully automated preparation of PET and therapeutic radiopharmaceuticals.

    Science.gov (United States)

    Kroselj, Marko; Socan, Aljaz; Zaletel, Katja; Dreger, Thorsten; Knopp, Roger; Gmeiner, Tanja; Kolenc Peitl, Petra

    2016-02-01

    With the vast development of theranostics and, recently, (68)Ga-radiolabeled molecules, there is also a need for novel, smaller, flexible, safe, and efficient modular automated synthesis systems in different clinical settings. The aim of our study was to determine the shielding properties of the modular self-shielded automated radiosynthesis box and determine its suitability for routine preparation of different radiopharmaceuticals to be used for diagnosis and therapy. To evaluate shielding properties, shielding factors were determined using two different radiation sources: (137)Cs and (68)Ga. The dose rates were measured at critical points at the surface and 1 m distance from the surface. Three different methods were used to concentrate and purify (68)Ga generator eluate. Performance of the system was tested by evaluating several radiolabeling applications using (68)Ga, (177)Lu, and (90)Y. Dose rates measured at the surface did not exceed 9 μSv/h for (68)Ga and 20 μSv/h when using (137)Cs. On average, dose rates at the surface were reduced for factors of 1665 and 906, respectively. Different DOTA peptides were labeled successfully with (68)Ga with radiochemical purities more than 94% using three different radiolabeling methods. (177)Lu-DOTATATE and (90)Y-DOTATATE were synthesized reproducibly with a radiochemical purity of more than 99% and more than 97%, respectively. A self-shielded radiosynthesis box is a unique solution for nuclear medicine departments that lack space for installation of standard automated synthesis systems set in large and heavy dedicated PET synthesis boxes. Shielding properties are sufficient for safe clinical use for both PET and β(-) radioisotopes. Because of its modular design and the simple adaptability of system parameters, the system can be used for the preparation of different clinically used radiopharmaceuticals and is also useful for research purposes.

  10. Preliminary studies of Technetium-99m-labeled antimyosin monoclonal antibody: development of radiopharmaceutical for cardiac evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Guilherme Luiz de Castro; Spencer, Patrick Jack; Muramoto, Emiko; Araujo, Elaine Bortoleti de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: glcarval@ipen.br

    2007-07-01

    In the acute myocardium infarction, the myocytes cell membrane loses its integrity, allowing the influx of extracellular macromolecules such as circulating antibody into the damaged cell. Specific antibodies to cardiac myosin can therefore bind to the acutely necrotic myocyte, allowing the noninvasive localization and dimension of myocardial infarction. Because of its favorable physical characteristics, low cost, and ready availability, technetium-99m ({sup 99m}Tc) is the radionuclide of choice for scintigraphy. The purpose of this work was to study the labeling of the antimyosin monoclonal antibody with ({sup 99m}Tc for development of a radiopharmaceutical with high sensitivity and specificity used in the diagnostic of the myocardial infarction. The intact monoclonal antibody (IgG{sub 1}) was reduced by treatment with dithiothreitol (DTT) with the consequent generation of free thiol groups (- SH), responsible for the labeling of the antibody with ({sup 99m}Tc. The radiochemical yield was determined using Sephadex G-25 column (PD-10). The percentage of ({sup 99m}Tc-antibody was 90,06% and after purification procedure the radiochemical yield was > 98%. The biodistribution studies showed low uptake in the stomach and thyroid at different times (1, 4 e 24 hours) representing a small amount of unbounded ({sup 99m}Tc and a good stability of the purified ({sup 99m}Tc-antibody. The uptake in the normal heart was relatively low as expected. Based on these results, we concluded that the direct labeling procedure applied to the antimyosin monoclonal antibody allowed the easy preparation of the radiopharmaceutical with good stability to be used in the noninvasive diagnostic of the myocardial infarction. (author)

  11. Radiopharmaceuticals in the elderly cancer patient: Practical considerations, with a focus on prostate cancer therapy: A position paper from the International Society of Geriatric Oncology Task Force.

    Science.gov (United States)

    Prior, John O; Gillessen, Silke; Wirth, Manfred; Dale, William; Aapro, Matti; Oyen, Wim J G

    2017-05-01

    Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e.g. myelosuppression). Since the introduction of Iodine-131 as a targeted therapy in thyroid cancer, several radiopharmaceuticals have been widely used. These include antibodies and peptides targeting specific epitopes on cancer cells. Among therapeutic bone seeking agents, radium-223 ((223)Ra) stands out as it results in survival gains in patients with castration-resistant prostate cancer and symptomatic bone metastases. The therapeutic use of radiopharmaceuticals in elderly cancer patients specifically has received little attention. In elderly prostate cancer patients, there may be advantages in radionuclides' ease of use and relative lack of toxicity compared with cytotoxic and cytostatic drugs. When using radionuclide therapies, close coordination between oncology and nuclear medicine is needed to ensure safe and effective use. Bone marrow reserve has to be considered. As most radiopharmaceuticals are cleared renally, dose adjustment may be required in the elderly. However, compared with younger patients there is less, if any, concern about adverse long-term radiation effects such as radiation-induced second cancers. Issues regarding the safety of medical staff, care givers and the wider environment can be managed by current precautions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. A simple low-cost of liquid I-131 dispenser for routine radiopharmaceutical dispensing at nuclear medicine department, Institut Kanser Negara

    Energy Technology Data Exchange (ETDEWEB)

    Said, M. A.; Suhaimi, N. E. F. [Fakulti Sains dan Teknologi, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi Selangor (Malaysia); Ashhar, Z. N., E-mail: aminhpj@gmail.com [Institut Kanser Negara, No 4, Jalan P7, Presint 7, 62250 Putrajaya (Malaysia); Zainon, R. [Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Kepala Batas, Pulau Pinang (Malaysia)

    2016-01-22

    In routine radiopharmaceutical Iodine-131 ({sup 131}I) dispensing, the amount of radiation dose received by the personnel depends on the distance between the personnel and the source, the time spent manipulating the source and the amount of shielding used to reduce the dose rate from the source. The novel iRAD-I131 dispenser using recycle {sup 131}I liquid lead pot will lead into low cost production, less maintenance and low dose received by the personnel that prepared the {sup 131}I. The new fabricated of low cost {sup 131}I dispenser was tested and the dose received by personnel were evaluated. The body of lead material is made from 2.5 cm lead shielded coated with epoxy paint to absorb the radiation dose up to 7.4 GBq of {sup 131} I. The lead pot was supported with two stainless steel rod. The Optically Stimulated Luminescence (OSL) nanodot was used in this study to measure the dose rate at both extremities for every personnel who prepared the {sup 131}I. Each OSL nanodot was attached at the fingertip. Three different personnel (experienced between one to ten years above in preparing the radiopharmaceuticals) were participated in this study. The average equivalent dose at right and left hand were 122.694 ± 121.637 µSv/GBq and 77.281 ± 62.146 µSv/GBq respectively. This study found that the dose exposure received using iRAD-I131 was less up to seven times compared to the conventional method. The comparison of experimental data using iRAD-I131 and established radiopharmaceutical dispenser was also discussed. The innovation of {sup 131}I dispenser is highly recommended in a small radiopharmaceutical facility with limited budget. The novel iRAD-I131 enables implementation of higher output liquid dispensing with low radiation dose to the personnel.

  13. Dose in the transport of radiopharmaceuticals. Change of perspective for reduction; Dosis en el transporte de radiofarmacos. Cambio de perspectiva para su reduccion

    Energy Technology Data Exchange (ETDEWEB)

    Acena Moreno, V.; Zamora Martin, F.; Rubio de Juan, E.

    2011-07-01

    This paper presents an analysis, covering a period of seven years, the doses received by workers in the transport sector, especially road transport of radiopharmaceuticals. This analysis details the reasons for the doses received by these workers, the measures have been adopted during this period for their reduction and additional measures would be required to achieve further reductions, taking into account the increase in recent years number of this type of transport and transport indices (TI) for some packages.

  14. Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP.

    Science.gov (United States)

    Lange, R; de Klerk, J M H; Bloemendal, H J; Ramakers, R M; Beekman, F J; van der Westerlaken, M M L; Hendrikse, N H; Ter Heine, R

    2015-05-01

    (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration. We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice. The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP. For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 μmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs. Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo. The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI)6]+

    OpenAIRE

    Faria,D.P.; Buchpiguel,C.A.; Marques, F.L.N.

    2015-01-01

    Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcoh...

  16. Detection of active alveolar bone destruction in human periodontal disease by analysis of radiopharmaceutical uptake after a single injection of 99m-Tc-methylene diphosphonate

    Energy Technology Data Exchange (ETDEWEB)

    Jeffcoat, M.K.; Williams, R.C.; Holman, B.L.; English, R.; Goldhaber, P.

    1986-01-01

    Previous studies have shown that, following a single injection of 99m-Tc-MDP, measurement of bone-seeking radiopharmaceutical uptake can detect ''active'' alveolar bone loss due to periodontal disease in beagle dogs, as determined by radiographs taken at the time of, and several months after, the nuclear medicine procedure. The efficacy of this diagnostic test, however, had not been assessed in human periodontal disease. The ability of a single boneseeking radiopharmaceutical uptake examination to detect ''active'' alveolar bone loss due to periodontal disease in human patients was assessed by comparing a single uptake measurement to the rate of bone loss determined from serial radiographs taken over a 6-month period. Uptake was expressed as a ratio of the cpm from the alveolar bone divided by the cpm from the non-tooth supporting bone of the nuchal crest. High uptake ratios were associated with ''active'' loss and low uptake ratios were associated with little if any change in alveolar bone height (p<0.001). The nuclear medicine examination was an accurate detector of periodontal disease activity in nearly 80% of the individual teeth studied. These data indicate that high bone-seeking radiopharmaceutical uptake ratios may be pathognomonic of active bone loss in human periodontal disease.

  17. Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI6]+

    Directory of Open Access Journals (Sweden)

    D.P. Faria

    2015-01-01

    Full Text Available Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75, Whatman 3MM paper and ethanol:chloroform (25:75, and the more expensive ITLC-SG and 1-propanol:chloroform (10:90 were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI6]+ since impurities such as 99mTc-reduced-hydrolyzed (RH, 99mTcO4 - and [99mTc(cysteine2]- complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

  18. Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI)6]+

    Science.gov (United States)

    Faria, D P; Buchpiguel, C A; Marques, F L N

    2015-03-03

    Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as 99mTc-reduced-hydrolyzed (RH), 99mTcO4 - and [99mTc(cysteine)2]- complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

  19. Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [(99m)Tc(MIBI)₆].

    Science.gov (United States)

    Faria, D P; Buchpiguel, C A; Marques, F L N

    2015-10-01

    Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [(99m)Tc(MIBI)₆]⁺ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [(99m)Tc(MIBI)₆]⁺ since impurities such as (99m)Tc-reduced-hydrolyzed (RH), (99m)TcO(4)(-) and [(99m)Tc(cysteine)₂]⁻ complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

  20. Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [{sup 99m}Tc(MIBI){sub 6}]{sup +}

    Energy Technology Data Exchange (ETDEWEB)

    Faria, D.P.; Buchpiguel, C.A.; Marques, F.L.N., E-mail: danielefaria1@gmail.com [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Faculdade de Medicina. Departamento de Radiologia. Servico de Medicina Nuclear

    2015-10-15

    Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [{sup 99m}Tc(MIBI){sub 6}]{sup +} as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol: chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol: chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [{sup 99m}Tc(MIBI){sub 6}]{sup +} since impurities such as {sup 99m}Tc-reduced-hydrolyzed (RH), {sup 99m}TcO4{sup -} and [{sup 99m}Tc(cysteine){sub 2}]{sup -} complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines. (author)

  1. Non-oncologic Applications of PET/CT and PET/MR in Musculoskeletal, Orthopedic, and Rheumatologic Imaging: General Considerations, Techniques, and Radiopharmaceuticals.

    Science.gov (United States)

    Gholamrezanezhad, Ali; Basques, Kyle; Batouli, Ali; Olyaie, Mojtaba; Matcuk, George; Alavi, Abass; Jadvar, Hossein

    2017-11-10

    Positron Emission Tomography (PET) is often underutilized in the field of musculoskeletal imaging, with key reasons including the excellent performance of conventional musculoskeletal MRI, the limited spatial resolution of PET, and the lack of reimbursement for PET for non-oncologic musculoskeletal indications. However, with improvements in PET/CT and PET/MR imaging over the last decade as well as an increased understanding of the pathophysiology of musculoskeletal diseases, there is an emerging potential for PET as a primary or complementary modality in the management of rheumatologic and orthopedic patients. Specific advantages of PET include the convenience of whole body imaging in a single session, the relative resilience of the modality in the imaging of metallic implants compared to CT and MRI, the ability to evaluate deep joints not amenable to palpation, and the potential for improved specificity of diagnosis with novel radiopharmaceuticals. In this review, we discuss multiple radiopharmaceuticals and technical consideration of PET/CT and PET/MRI that can be employed in imaging of non-tumoral bone and soft tissue disorders. Both PET/CT and PET/MR hold significant promise in the field of musculoskeletal imaging, and with further radiopharmaceutical development and clinical research, these hybrid modalities can potentially transform the current management of patients with orthopedic and rheumatologic disease. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  2. Environmental effects on the structure of metal ion-DOTA complexes: An ab initio study of radiopharmaceutical metals.

    Energy Technology Data Exchange (ETDEWEB)

    Lau, E Y; Lightstone, F C; Colvin, M E

    2006-02-10

    Quantum mechanical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA; but, Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the coordination energy for the amide arm shows a large variation between the Y and In ions. Optimizations including water and guandinium moieties to approximate the effects of antibody binding indicate a large energy cost for the DOTA-chelated In to adopt the ideal conformation for antibody binding.

  3. Preparation, chromatographic evaluation and biodistribution of {sup 99m}Tc-procainamide as a radiopharmaceutical for heart imaging

    Energy Technology Data Exchange (ETDEWEB)

    Motaleb, M.A.; Ibrahim, I.T.; Abo Rizq, R.S. [Atomic Energy Authority, Cairo (Egypt). Labeled Compound Dept.; Elzanfaly, E.S. [Cairo Univ. (Egypt). Analytical Dept.

    2017-06-01

    Procainamide (4-amino-N-[2-(diethylamino) ethyl] benzamide) is a sodium channel blocker, which acts as an effective antiarrhythmic agent used in the treatment of a variety of atrial and ventricular arrhythmias. The aim of this study was to prepare {sup 99m}Tc-procainamide complex, apply different chromatographic techniques for the assay of radiolabeling yield and study its biodistribution as a novel radiopharmaceutical for heart imaging. {sup 99m}Tc-procainamide was obtained with a maximum labeling yield of 95.76±0.20% via direct labeling method under optimum conditions of 200 μg of procainamide, 300 μL of buffer (carbonate) at pH 11, 30 μg SnCl{sub 2} . 2H{sub 2}O at room temperature (25 C) for 15 min. In terms of in vitro stability, the complex was stable for 3 h. Chromatographic evaluation using paper chromatography, thin layer chromatography, gel chromatography, and high performance liquid chromatography showed reliable results for measuring the radiochemical yield. Biodistribution study of {sup 99m}Tc-procainamide showed ratios of heart/lung and heart/liver (6.38±1.50, 2.06±0.31, respectively at 30 min post injection) which was comparable to that of {sup 99m}Tc-sestamibi (7.4±2.00, 0.97±0.10, respectively at 60 min, P<0.05).

  4. Theranostic Role of 32P-ATP as Radiopharmaceutical for the Induction of Massive Cell Death within Avascular Tumor Core.

    Science.gov (United States)

    Galiè, Mirco; Boschi, Federico; Scambi, Ilaria; Merigo, Flavia; Marzola, Pasquina; Altabella, Luisa; Lavagnolo, Umberto; Sbarbati, Andrea; Spinelli, Antonello E

    2017-01-01

    Drug inaccessibility to vast areas of the tumor parenchyma is amongst the major hurdles for conventional therapies. Treatment efficacy rapidly decreases with distance from vessels and most of the tumor cells survive therapy. Also, between subsequent cycles of treatment, spared cancer cells replace those killed near the vessels, improving their access to nutrients, boosting their proliferation rate, and thus enabling tumor repopulation. Because of their property of "acting at a distance," radioisotopes are believed to overcome the physical barrier of vascular inaccessibility. Methods A novel molecular imaging tool called Cerenkov Luminescence Imaging (CLI) was employed for the detection of Cerenkov radiation emitted by beta particles, allowing in vivo tracking of beta-emitters. More precisely we investigated using a xenograft model of colon carcinoma the potential use of 32P-ATP as a novel theranostic radiopharmaceutical for tracing tumor lesions while simultaneously hampering their growth. Results Our analyses demonstrated that 32P-ATP injected into tumor-bearing mice reaches tumor lesions and persists for days and weeks within the tumor parenchyma. Also, the high-penetrating beta particles of 32P-ATP exert a "cross-fire" effect that induces massive cell death throughout the entire tumor parenchyma including core regions. Conclusion Our findings suggest 32P-ATP treatment as a potential approach to complement conventional therapies that fail to reach the tumor core and to prevent tumor repopulation.

  5. SU-C-303-03: Dosimetric Model of the Beagle Needed for Pre-Clinical Testing of Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Shang, M; Sands, M; Bolch, W [University of Florida, Gainesville, FL (United States)

    2015-06-15

    Purpose: Large animal models, most popularly beagles, have been crucial surrogates to humans in determining radiation safety levels of radiopharmaceuticals. This study aims to develop a detailed beagle phantom to accurately approximate organ absorbed doses for therapy nuclear medicine preclinical studies. Methods: A 3D NURBS model was created subordinate to a whole body CT of an adult beagle. Bones were harvested and CT imaged to offer macroscopic skeletal detail. Samples of trabecular spongiosa were cored and imaged to offer microscopic skeletal detail for bone trabeculae and marrow volume fractions. Results: Organ masses in the model are typical of an adult beagle. Trends in volume fractions for skeletal dosimetry are fundamentally similar to those found in existing models of other canine species. Conclusion: This work warrants its use in further investigations of radiation transport calculation for electron and photon dosimetry. This model accurately represents the anatomy of a beagle, and can be directly translated into a useable geometry for a voxel-based Monte Carlo radiation transport program such as MCNP6. Work supported by a grant from the Hyundai Hope on Wheels Foundation for Pediatric Cancer Research.

  6. Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy.

    Science.gov (United States)

    Mukherjee, Archana; Lohar, Sharad; Dash, Ashutosh; Sarma, Haladhar Dev; Samuel, Grace; Korde, Aruna

    2015-04-01

    The clinical applications of radiolabeled somatostatin analogue (177) Lu-DOTA-Tyr(3) -Thr(8) -Octreotide ((177) Lu-DOTATATE) constitute a promising treatment option for patients with disseminated and inoperable neuroendocrine (NET) tumors. Formulation of (177) Lu-DOTATATE in hospital radiopharmacy under aseptic conditions in a safe and reliable manner is a major constraint for its extensive use. The present work was intended to develop a kit for the safe preparation of the therapeutic radiopharmaceutical, viz. (177) Lu-DOTATATE of high quality that can be easily adapted at conventional hospital radiopharmacies. Single vial kits of DOTATATE were formulated and evaluated for suitability for radiolabeling as well as stability on its storage. Patient dose of (177) Lu-DOTATATE (7.4 GBq) could be successfully prepared using semi-automated in-house setup that assures safe handling and high yields of product of pharmaceutical purity suitable for clinical use. Fast clearance of activity via renal route was observed in preclinical biodistribution studies of (177) Lu-DOTATATE carried out in normal Swiss mice. Deployment of in-house produced (177) LuCl3 , cold kits and easy adaptability of synthesis setup at hospital radiopharmacy for preparation is likely to expand applications of peptide receptor radionuclide therapy. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Performance of the radionuclide calibrators used at Division of Radiopharmaceuticals Production of the CRCN-NE, Recife, PE, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Fragoso, Maria Conceicao de Farias; Albuquerque, Antonio Morais de Sa; Oliveira, Mercia L.; Lima, Fernando Roberto de Andrade [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    The radionuclide calibrators are essential instruments in nuclear medicine services to determine the activity of radiopharmaceuticals which will be administered to the patients. Essentially, it consists of a well-type ionization chamber coupled to a special displaying electronic circuit which allows one visualize the instrument response in activity units. Inappropriate performance of these equipment may lead to underestimation or overestimation of the activity, compromising the success of diagnosis or therapy. Quality control describes the procedures by which one can assure quality of activity measurement, providing efficacy of nuclear medicine procedures that employ unsealed sources of radioactivity. Several guides of national and international organizations summarize the recommended tests for the quality control of the radionuclide calibrators: accuracy, precision, reproducibility, linearity and geometry. The aim of this work was to establish a quality control program on the radionuclide calibrators from Divisao de Producao de Radiofarmacos (DIPRA) of the Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE), Brazil, utilized as reference instruments on comparison of activities measurements.. The results were determined and compared to the references values recommended by national and international guides. Besides, the geometry test provided the correction factors to be applied in activity measurements in different containers, in different volumes and in different positions. (author)

  8. The twenty-third report on survey of the adverse reaction to radiopharmaceuticals (The 26th survey in 2000)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-02-01

    The survey in the title involves occasions of adverse reactions and drug defects of radiopharmaceuticals and its 26th one in 2000 (April 1, 2000-March 31, 2001) is reported herein. The survey was conducted by questionnaire to 1,212 facilities, of which 1,044 (86.1%) answered. Adverse reaction (24 cases/1,401,962 in total cases of administration=0.0017% occasion) and drug defect (3 cases, 0.0002%) were reported from 25 facilities: They were 0.0017-0.0025% and 0.0001-0.0006%, respectively, after 1996. Most frequent occasion (203/100,000 examinations) of adverse reaction was seen in {sup 131}I-methyl-norcholesterol, which had been considered to be due to the ingredient, ethanol. Occasion of the adverse reaction of other drugs were less than 47/100,000 examinations. Three cases of the drug defect were poor distribution (2) ({sup 99m}Tc-HMDP) and poor labeling (1) ({sup 99m}Tc-tetrofosmin). (K.H.)

  9. Studies on 177Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation.

    Science.gov (United States)

    Abbasi, Imtiaz Ahmed

    2011-04-01

    (99m)Tc-MDP (technetium-99(m)-labeled methylene diphosphonate) has been widely used as a radiopharmaceutical for bone scintigraphy in cases of metastatic bone disease. (177)Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. No study on preparing a complex of (177)Lu with MDP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking (177)Lu-MDP (lutetium-177-labeled MDP) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. Biodistribution studies after intravenous injection of (177)Lu-MDP complex in rats may yield important information to assess its potential for clinical use as a bone pain palliation agent for the treatment of bone metastases. (177)Lu was produced by irradiating natural Lu(2)O(3) (10 mg) target at a thermal flux ∼ 8.0 × 10(13) n/cm(2) per second for 12 h in the swimming pool-type reactor.(177)Lu was labeled with MDP by adding nearly 37 MBq (1.0 mCi) of (177)LuCl(3) to a vial containing 10 mg MDP. The radiochemical purity and labeling efficiencies were determined by thin layer chromatography. Labeling of (177)Lu with MDP was optimized, and one sample was subjected to high-performance liquid chromatography (HPLC) analysis. Twelve Sprague-Dawley rats were injected with 18.5 MBq (0.5 mCi). (177)Lu-MDP in a volume of 0.1 ml was injected intravenously and then sacrificed at 2 min, 1 h, 2 h and 22 h (three rats at each time point) after injection. Samples of various organs were separated, weighed and measured for radioactivity and expressed as percent uptake of injected dose per gram. Bioevaluation studies with rats under gamma-camera were also performed to verify the results. The quality control using thin layer chromatography has shown >99% radiochemical purity of (177)Lu-MDP complex. Chromatography with Whatman 3MM paper showed maximum labeling at pH = 6, incubation time = 30 min, and ligand/metal ratio = 60

  10. Studies on {sup 177}Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Imtiaz Ahmed, E-mail: imtiaz_abbasi@yahoo.co

    2011-04-15

    Objective: {sup 99m}Tc-MDP (technetium-99{sup m}-labeled methylene diphosphonate) has been widely used as a radiopharmaceutical for bone scintigraphy in cases of metastatic bone disease. {sup 177}Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. No study on preparing a complex of {sup 177}Lu with MDP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking {sup 177}Lu-MDP (lutetium-177-labeled MDP) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. Biodistribution studies after intravenous injection of {sup 177}Lu-MDP complex in rats may yield important information to assess its potential for clinical use as a bone pain palliation agent for the treatment of bone metastases. Methods: {sup 177}Lu was produced by irradiating natural Lu{sub 2}O{sub 3} (10 mg) target at a thermal flux {approx}8.0x10{sup 13} n/cm{sup 2} per second for 12 h in the swimming pool-type reactor.{sup 177}Lu was labeled with MDP by adding nearly 37 MBq (1.0 mCi) of {sup 177}LuCl{sub 3} to a vial containing 10 mg MDP. The radiochemical purity and labeling efficiencies were determined by thin layer chromatography. Labeling of {sup 177}Lu with MDP was optimized, and one sample was subjected to high-performance liquid chromatography (HPLC) analysis. Twelve Sprague-Dawley rats were injected with 18.5 MBq (0.5 mCi). {sup 177}Lu-MDP in a volume of 0.1 ml was injected intravenously and then sacrificed at 2 min, 1 h, 2 h and 22 h (three rats at each time point) after injection. Samples of various organs were separated, weighed and measured for radioactivity and expressed as percent uptake of injected dose per gram. Bioevaluation studies with rats under gamma-camera were also performed to verify the results. Results: The quality control using thin layer chromatography has shown >99% radiochemical purity of {sup 177}Lu-MDP complex. Chromatography with Whatman 3

  11. {sup 177}Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Rajabi, Hossein, E-mail: hrajabi@modares.ac.i [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, 14115-331 Tehran (Iran, Islamic Republic of)

    2010-11-15

    Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of {sup 177}Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 {mu}g ml{sup -1}, {sup 177}Lu-Herceptin (surviving cells: 5{+-}0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43{+-}3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems.

  12. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)], E-mail: laura.melendez@unipd.it; Nadali, Anna; Zangoni, Elena [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy); Banzato, Alessandra; Rondina, Maria [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Rosato, Antonio [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Istituto Oncologico Veneto, IOV, Padova, Padua (Italy); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)

    2009-08-15

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47{+-}5.11% of the injected dose). The liver MTD in mice was {approx}40 Gy after 7.4 MBq of {sup 188}Re-HA injection. Conclusions: {sup 188}Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

  13. Multielemental determination of trace elements in radiopharmaceuticals produced at the radiopharmacy center using ICP-OES technique

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, Angelica T.; Martins, Patricia de A.; Fukumori, Neuza T.O.; Mengatti, Jair; Matsuda, Margareth M.N., E-mail: angelicatamiao@gmail.com, E-mail: patyosborne@yahoo.com, E-mail: ntfukuma@ipen.br, E-mail: mengatti@ipen.br, E-mail: mmatsuda@ipen.br [Institito de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    The control of chemical impurities in radiopharmaceuticals is critical to their safety and efficacy. According to the U.S. Pharmacopeia (USP), the elemental impurities with potential toxicity must be quantified. A proposed revision of USP 35 introduces the technique of atomic emission spectrometry for the analysis of elements. The aim of this work was to study the concentration of chemicals elements in FDG-Fluor-18, IPEN-TEC Generator and MIBI-TEC using an ICP-OES technique. One analytical curve composed by 27 elements (Ag, A1, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ga, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Pd, Se, Sr, Te, T1, Zn) was constructed in two analytical ranges. The analyses were carried out simultaneously in an ICP-OES Vista MPX (Agilent). Some parameters for analysis and method validation were evaluated. The cleaning and maintenance of equipment influenced the emission intensity of the elements. 1.2 power and 10s sample uptake resulted in a consumption of 1.6 mL of sample and Mg II/Mg I ratio relation equal to 9.40. Linearity, LOD and LOQ were determined. The analysis were performed using 1:40 dilution with purified water. The main elements studied in this work were A1, Cu and Zn. The % recovery was determined with final concentrations of 0.3, 0.5 and 0.8 μg mL{sup -1}. The analyses were performed in triplicate with three different batches. The % recovery was between 96.65 and 117.61% and the values for precision (CV) were less than 5% indicating good accuracy of the method. (author)

  14. Non invasive scintigraphic method for biodistribution study of radiopharmaceuticals; Metodo cintilografico nao invasivo para estudo de biodistribuicao de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Erika V.; Silva, Natanael G.; Freire, Antonio C.; Monteiro, Elisiane de G.; Benedetti, Stella; Muramoto, Emiko; Fukumori, Neuza T.O.; Matsuda, Margareth M.N., E-mail: erikavieira@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia; Vasconcellos, Marina B.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisa

    2011-07-01

    Biodistribution studies can be done by invasive or noninvasive methods. The aim of this study was to evaluate the percentage of retained dose (RD) in the organs of interest in noninvasive and invasive study of biodistribution of {sup 99m}Tc-DMSA (dimercaptosuccinic acid), {sup 99m}Tc-MAA (macro aggregated human serum albumin) and {sup 99m}Tc-MDP (methylene diphosphonate) and to compare with the invasive method described in the United States Pharmacopoeia (USP). Lyophilized reagents (DMSA, MAA and MDP) and sodium pertechnetate was obtained from IPEN-CNEN/SP. The radioactive concentration was 123 MBq mL{sup -1} ({sup 99m}Tc-DMSA and {sup 99m}Tc-MAA) and 617 MBq mL{sup -1} ({sup 99m}Tc-MDP). {sup 99m}Tc-DMSA and {sup 99m}Tc-MDP were injected via the tail vein and {sup 99m}Tc-MAA in the penile vein of rats. The scintigraphic images were obtained in a Nucline TH/22 Mediso gamma camera. The animals were sacrificed after the acquisition of images. The organs were removed and the activity of each organ of interest was measured in an ionization chamber. The renal uptake of {sup 99m}Tc-DMSA by noninvasive method was (47,02 +- 2,87)% up to (49,37 +- 3,41)%. By the invasive method it was observed RD (49.27 +- 1.88)%. The %RD of {sup 99m}Tc-MAA in the lungs by non-invasive method varied from (94,22 +- 0,17)% to (94,67 +- 0,25)%. Bone scintigraphy with {sup 99m}Tc-MDP showed significant uptake in the skeleton. The method proposed for noninvasive scintigraphic study biodistribution of radiopharmaceuticals was feasible, with results comparable to those obtained by invasive method described in USP. (author)

  15. Non invasive scintigraphic method for biodistribution study of radiopharmaceuticals; Metodo cintilografico nao invasivo para estudo de biodistribuicao de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Erika V.; Silva, Natanael G.; Freire, Antonio C.; Monteiro, Elisiane de G.; Benedetti, Stella; Muramoto, Emiko; Fukumori, Neuza T.O.; Matsuda, Margareth M.N., E-mail: erikavieira@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia; Vasconcellos, Marina B.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisa

    2010-07-01

    Biodistribution studies can be done by invasive or noninvasive methods. The aim of this study was to evaluate the percentage of retained dose (RD) in the organs of interest in noninvasive and invasive study of biodistribution of {sup 99m}Tc-DMSA (dimercaptosuccinic acid), {sup 99m}Tc-MAA (macro aggregated human serum albumin) and {sup 99m}Tc-MDP (methylene diphosphonate) and to compare with the invasive method described in the United States Pharmacopoeia (USP). Lyophilized reagents (DMSA, MAA and MDP) and sodium pertechnetate was obtained from IPEN-CNEN/SP. The radioactive concentration was 123 MBq mL{sup -1} ({sup 99m}Tc-DMSA and {sup 99m}Tc-MAA) and 617 MBq mL{sup -1} ({sup 99m}Tc-MDP). {sup 99m}Tc-DMSA and {sup 99m}Tc-MDP were injected via the tail vein and {sup 99m}Tc-MAA in the penile vein of rats. The scintigraphic images were obtained in a Nucline TH/22 Mediso gamma camera. The animals were sacrificed after the acquisition of images. The organs were removed and the activity of each organ of interest was measured in an ionization chamber. The renal uptake of {sup 99m}Tc-DMSA by noninvasive method was (47,02 {+-} b 2,87)% up to (49,37 {+-} b 3,41)%. By the invasive method it was observed RD (49.27 {+-} b 1.88)%. The %RD of {sup 99}mTc-MAA in the lungs by non-invasive method varied from (94,22 {+-} b 0,17)% to (94,67 {+-} b 0,25)%. Bone scintigraphy with {sup 99}mTc-MDP showed significant uptake in the skeleton. The method proposed for noninvasive scintigraphic study biodistribution of radiopharmaceuticals was feasible, with results comparable to those obtained by invasive method described in USP. (author)

  16. Applying quality by design principles to the small-scale preparation of the bone-targeting therapeutic radiopharmaceutical rhenium-188-HEDP.

    Science.gov (United States)

    Lange, Rogier; Ter Heine, Rob; van der Gronde, Toon; Selles, Suzanne; de Klerk, John; Bloemendal, Haiko; Hendrikse, Harry

    2016-07-30

    Rhenium-188-HEDP ((188)Re-HEDP) is a therapeutic radiopharmaceutical for treatment of osteoblastic bone metastases. No standard procedure for the preparation of this radiopharmaceutical is available. Preparation conditions may influence the quality and in vivo behaviour of this product. In this study we investigate the effect of critical process parameters on product quality and stability of (188)Re-HEDP. A stepwise approach was used, based on the quality by design (QbD) concept of the ICH Q8 (Pharmaceutical Development) guideline. Potential critical process conditions were identified. Variables tested were the elution volume, the freshness of the eluate, the reaction temperature and time, and the stability of the product upon dilution and storage. The impact of each variable on radiochemical purity was investigated. The acceptable ranges were established by boundary testing. With 2ml eluate, adequate radiochemical purity and stability were found. Nine ml eluate yielded a product that was less stable. Using eluate stored for 24h resulted in acceptable radiochemical purity. Complexation for 30min at room temperature, at 60°C and at 100°C generated appropriate and stable products. A complexation time of 10min at 90°C was too short, whereas heating 60min resulted in products that passed quality control and were stable. Diluting the end product and storage at 32.5°C resulted in notable decomposition. Two boundary tests, an elution volume of 9ml and a heating time of 10min, yielded products of inadequate quality or stability. The product was found to be instable after dilution or when stored above room temperature. Our findings show that our previously developed preparation method falls well within the proven acceptable ranges. Applying QbD principles is feasible and worthwhile for the small-scale preparation of radiopharmaceuticals. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Cu(II) Bis(thiosemicarbazone) Radiopharmaceutical Binding to Serum Albumin: Further Definition of Species-Dependence and Associated Substituent Effects

    Science.gov (United States)

    Basken, Nathan E.; Green, Mark A.

    2009-01-01

    Introduction The Cu-PTSM (pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II)) and Cu-ATSM (diacetyl bis(N4-methylthiosemicarbazonato)copper(II)) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)) radiopharmaceutical appears to only exhibit non-specific binding to human and animal serum albumins. Methods To further probe the structural basis for the species-dependence of this albumin binding interaction, protein binding of these three radiopharmaceuticals was examined in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat, elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Results Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species-dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. Conclusions The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate. PMID:19520290

  18. Evaluation of Deoxyribonucleic Acid Toxicity Induced by the Radiopharmaceutical 99mTechnetium-Methylenediphosphonic Acid and by Stannous Chloride in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Adriano Caldeira-de-Araujo

    2012-11-01

    Full Text Available Radiopharmaceuticals are employed in patient diagnostics and disease treatments. Concerning the diagnosis aspect, technetium-99m (99mTc is utilized to label radiopharmaceuticals for single photon computed emission tomography (SPECT due to its physical and chemical characteristics. 99mTc fixation on pharmaceuticals depends on a reducing agent, stannous chloride (SnCl2 being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the 99mTc-MDP(methylene diphosphonate used for bone SPECT and SnCl2 were evaluated in Wistar rat blood cells using the Comet assay and micronucleus test. The experimental approach was to endovenously administer NaCl 0.9% (negative control, cyclophosphamide 50 mg/kg b.w. (positive control, SnCl2 500 μg/mL or 99mTc-MDP to animals and blood samples taken immediately before the injection, 3, and 24 h after (in the Comet assay and 36 h after, for micronucleus test. The data showed that both SnCl2 and 99mTc-MDP-induced deoxyribonucleic acid (DNA strand breaks in rat total blood cells, suggesting genotoxic potential. The 99mTc-MDP was not able to induce a significant DNA strand breaks increase in in vivo assays. Taken together, the data presented here points to the formation of a complex between SnCl2 in the radiopharmaceutical 99mTc-MDP, responsible for the decrease in cell damage, compared to both isolated chemical agents. These findings are important for the practice of nuclear medicine.

  19. (131)I-trazodone: preparation, quality control and in vivo biodistribution study by intranasal and intravenous routes as a hopeful brain imaging radiopharmaceutical.

    Science.gov (United States)

    Motaleb, M A; Ibrahim, I T; Sayyed, M E; Awad, G A S

    The preparation of (131)I-trazodone hydrochloride and its biological evaluation as a promising brain imaging radiopharmaceutical using two routes of administration. Trazodone (TZ) was radiolabelled with (131)I using direct electrophilic substitution, and different factors affecting labelling yield were studied. Quality control of (131)I-TZ was carried out using ascending paper chromatography, paper electrophoresis, and high pressure liquid chromatography (HPLC). In vivo biodistribution of (131)I-TZ was evaluated in Swiss albino mice using 3 methods: intravenous (131)I-TZ solution (IVS), intranasal (131)I-TZ solution (INS), and intranasal (131)I-TZ microemulsion (INME). Optimum labelling yield of 91.23±2.12% was obtained with in vitro stability of (131)I-TZ up to 6h at room temperature. The biodistribution results showed a notably higher and sustained brain uptake for INME compared to IVS and INS at all time intervals. In addition, heart and blood uptake levels for INME were lower than those for IV solution which, in turn, could decrease the systemic side effects of trazodone. Also, the (131)I-trazodone INME brain uptake of 6.7±0.5%ID/g was higher than that of (99m)Tc-ECD and (99m)Tc-HMPAO (radiopharmaceuticals currently used for brain imaging). (131/123)I-trazodone formulated as INME could be used as a promising radiopharmaceutical for brain imaging. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  20. ⁶⁸Ge content quality control of ⁶⁸Ge/⁶⁸Ga-generator eluates and ⁶⁸Ga radiopharmaceuticals--a protocol for determining the ⁶⁸Ge content using thin-layer chromatography.

    Science.gov (United States)

    Eppard, Elisabeth; Loktionova, Natalia S; Rösch, Frank

    2014-09-01

    (68)Ge breakthrough from a (68)Ge/(68)Ga-generator appears to be one of the most critical parameters for the routine clinical application of this generator and (68)Ga-radiopharmaceuticals. We report a TLC-based (thin-layer chromatography) protocol which allows the (68)Ge breakthrough of a generator to be determined within 1 h post-initial elution. The protocol can also be adapted to allow the (68)Ge content of a (68)Ga-radiopharmaceutical preparation to be determined prior to in vivo application. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Evaluation of radiochemistry purity and p H of radiopharmaceuticals in nuclear medicine services at Pernambuco, Brazil; Avaliacao da pureza radioquimica e pH de radiofarmacos em servicos de medicina nuclear de Pernambuco, Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Wellington; Lima, Fabiana Farias de, E-mail: falima@cnen.gov.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Santos, Poliane A.L.; Lima, Fernando Roberto de Andrade; Lima, Fabiana Farias de, E-mail: fflima@cnen.gov.b [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    Radiopharmaceuticals are cellular or molecular structures that have a radionuclide in its composition and they are used for diagnosing or treating diseases. The evaluation of the radiochemical purity of radiopharmaceuticals is essential to produce images with artifacts free, as well as avoid unnecessary absorbed dose to the patient. Since they are administered in humans is important and necessary that they undergo rigorous quality control. Due to this fact, the norm in ANVISA RDC 38/2008 declaring the mandatory completion of a minimum of tests in routine nuclear medicine services before human administration. (author)

  2. The synthesis and biological evaluation of integrin receptor targeting molecules as potential radiopharmaceuticals

    Science.gov (United States)

    Pellegrini, Paul

    This thesis reports on the synthesis, characterisation and biological evaluation of a number of metal complexes designed to interact with the alphavbeta3 integrin receptor, an important biological target that is heavily involved in angiogenesis, and thus cancer related processes. Two approaches were used to synthesise the integrin-avid targets. The first was to attach a variety of bifunctional chelators (BFC's) for the incorporation of different metal centres to a known integrin antagonist, L-748,415, developed by Merck. The BFC's used were the hydrazinonicotinamide (HYNIC) and monoamine monoamide dithiol (MAMA) systems for coordination to Tc-99m and rhenium of which was used as a characterization surrogate for the unstable Tc core. The 1,4,7,10-tetraazacyclotridecanetetraacetic acid (TRITA) BFC was attached for the inclusion of copper and lutetium. This 'conjugate' approach was designed to yield information on how the BFC and the linker length would affect the affinity for the integrin receptor. The second approach was an 'integrated' method where the chelation moiety was integral to the biologically relevant part of the molecule, which in the case of the alphavbeta3 integrin receptor, is the arginine-glycine-aspartic acid (RGD) mimicking sequence. Two complexes were created with a modified MAMA derivative placed between a benzimidazole moiety (arginine mimick) and the aspartic acid mimicking terminal carboxylic acid to see how it would affect binding while keeping the molecular weight relatively low. The molecules were tested in vitro against purified human alphavbeta3 integrin receptor protein in a solid phase receptor binding assay to evaluate their inhibition constants against a molecule of known high affinity and selectivity in [I125]L-775,219, the I125 labelled alphavbeta3 integrin antagonist. The radiolabelled analogues were also tested in vivo against the A375 human melanoma cell line transplanted into balb/c nude mice as well as Fischer rats implanted

  3. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Directory of Open Access Journals (Sweden)

    Deise Elizabeth Souza

    2011-01-01

    Full Text Available Cassia angustifolia Vahl (senna is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract.

  4. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos, E-mail: marciaoliveira.13@terra.com.b [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia Experimental; Fonseca, Adenilson de Souza da [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. Biomedico. Dept. de Ciencias Fisiologicas; Bernardo-Filho, Mario [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil). Coordenadoria de Pesquisa

    2011-07-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m ({sup 99m}Tc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na{sup 99m}TcO{sub 4}) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na{sup 99m}TcO{sub 4} and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na{sup 99m}TcO{sub 4} in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na{sup 99m}TcO{sub 4} are conducted in patients who are using senna extract. (author)

  5. Intraoperative bone and bone marrow sampling: a simple method for accurate measurement of uptake of radiopharmaceuticals in bone and bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Oyen, W.J.G.; Buijs, W.C.A.M.; Kampen, A. van; Koenders, E.B.; Claessens, R.A.M.J.; Corstens, F.H.M. (University Hospital, Nijmegen (Netherlands))

    1993-02-01

    Accurate estimation of bone marrow uptake of radiopharmaceuticals is of crucial importance for accurate whole body dosimetry. In this study, a method for obtaining normal bone marrow and bone during routine surgery without inconvenience to volunteers is suggested and compared to an indirect method. In five volunteers (group 1), 4 MBq [sup 111]In-labelled human polyclonal IgG ([sup 111]In-IgG) was administered 48h before placement of a total hip prosthesis. After resection of the femoral head and neck, bone marrow was aspirated from the medullary space with a biopsy needle. In five patients, suspected of having infectious disease (group 2), bone marrow uptake was calculated according to a well-accepted method using regions of interest over the lumbar spine, 48h after injection of 75 MBq [sup 111]In-IgG. Bone marrow uptake in group 1 (4.5 [+-]1.3%D kg[sup -1]) was significantly lower than that in group 2 (8.5 [+-] 2.1%D kg[sup -1]) (P<0.01). Blood and plasma activity did not differ significantly for both groups. This method provides a system for directly and accurately measuring uptake and retention in normal bone marrow and bone of all radiopharmaceuticals at various time points. It is a safe and simple procedure without any discomfort to the patient. Since small amounts of activity are sufficient, the radiation dose to the patient is low. (author).

  6. A rapid kinetic chromogenic method for quantification of bacterial endotoxins in lyophilized reagents for labeling with {sup 99m}Tc radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Fukumori, Neuza T.O.; Campos, Domingos G.; Silva, Laercio; Fernandes, Adriana V.; Mengatti, Jair; Silva, Constancia P.G.; Matsuda, Margareth M.N. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    A rapid quantitative kinetic chromogenic test in an automated Portable Test System (PTS) has been developed for determination of bacterial endotoxins in water, in-process and end-products using the Limulus amebocyte lysate (LAL). The aim of this work was to validate the method for lyophilized reagents for labeling with {sup 99m}Tc radiopharmaceuticals with no interfering factors. Experiments were performed in three consecutive batches of the lyophilized reagents Methylenediphosphonic Acid (MDP) and Pyrophosphate (PYRO) produced at IPEN-CNEN/ SP using the PTS from Endosafe, Inc.{sup TM}, Charleston, SC. The Maximum Valid Dilution (MVD) was calculated to establish the extent of dilution to avoid interfering test conditions (MVD=500). Better results were obtained above 1:20 dilution factor for MDP and 1:100 for PYRO. The parameters of coefficient correlation (R) -0.980, RPPC between 50 - 200% and coefficient variation (CV) of the samples less than 25% were satisfied and the endotoxin concentration was lower than the lowest concentration of the standard curve (0.05 EU mL{sup -1}), therefore less than the established limit in pharmacopoeias. The PTS is a rapid, simple and accurate technique using the quantitative kinetic chromogenic method for bacterial endotoxin determination. For this reason, it is very practical in the radiopharmaceutical area and it trends to be the method of choice for the pyrogen test. For MDP and PYRO, the validation was successfully performed. (author)

  7. Beyond current guidelines: reduction in minimum administered radiopharmaceutical activity with preserved diagnostic image quality in pediatric hepatobiliary scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Fahey, Frederic; Markelewicz, Robert; Grant, Frederick; Drubach, Laura; Treves, S. Ted [Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston Children' s Hospital, Boston, MA (United States); Harvard Medical School, Joint Program in Nuclear Medicine, Boston (United States); Zukotynski, Katherine [University of Toronto, Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto (Canada); Harvard Medical School, Joint Program in Nuclear Medicine, Boston (United States); Zurakowski, David [Boston Children' s Hospital, Departments of Anesthesia and Surgery, Boston (United States); Falone, Anthony; Vitello, Marie; Cao, Xinhua [Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston Children' s Hospital, Boston, MA (United States); Vija, A.H.; Bhattacharya, Manojeet; Ding, Xinhong [Siemens Medical Solutions USA, Inc., Molecular Imaging, Malvern, PA (United States); Bar-Sever, Zvi [Schneider Children' s Medical Center, Petach Tikvah (Israel); Tel-Aviv University, Tel-Aviv (Israel); Gelfand, Michael [Cincinnati Children' s Hospital, Cincinnati, OH (United States)

    2014-12-15

    To determine if the minimum administered radiopharmaceutical activity for hepatobiliary scintigraphy can be reduced while preserving diagnostic image quality using enhanced planar processing (EPP). A total of 40 infants between 10 and 270 days old (body mass 2.2 - 6.5 kg) had hepatobiliary scintigraphy during the period 2004 - 2010 following the intravenous administration of either {sup 99m}Tc-mebrofenin (18 patients) or {sup 99m}Tc-disofenin (22 patients). Due to the small size of these patients, they all received the minimum administered activity of 18.5 MBq consistent with the North American Consensus Guidelines. Six nuclear medicine physicians subjectively graded the acceptability of the image quality for clinical interpretation using a four-point scale (not acceptable, fair, good, excellent). Each physician independently graded seven image sets including the original study (full activity) and simulated reduced activity studies using binomial subsampling (50 % of full activity, 25 % of full activity and activity reduced by weight), with and without EPP. For full-activity studies, 98 % were deemed acceptable by the six physicians for clinical interpretation. The percentages of acceptable 50 % reduced activity studies with and without EPP were not significantly different from the percentage of acceptable full-activity studies (P = 0.193 and P = 0.998, respectively). The percentage of acceptable 25 % reduced activity studies without EPP was significantly different from the percentage of acceptable full-activity studies (P < 0.001); however, this difference vanished when EPP was applied (P = 0.482). The activity reduced by weight ranged from 1.85 to 4.81 MBq (10 % to 26 % of full dose) and the percentages of acceptable studies with and without EPP were significantly different from the percentage of acceptable full-activity studies (P < 0.001 and P = 0.02, respectively). Clinically interpretable hepatobiliary scintigraphy images can be obtained in infants when the

  8. A tyrosine kinase inhibitor-based high-affinity PET radiopharmaceutical targets vascular endothelial growth factor receptor.

    Science.gov (United States)

    Li, Feng; Jiang, Sheng; Zu, Youli; Lee, Daniel Y; Li, Zheng

    2014-09-01

    Tyrosine kinase receptors including vascular endothelial growth factor receptor (VEGFR) have gained significant attention as pharmacologic targets. However, clinical evaluation of small-molecule drugs or biologics that target these pathways has so far yielded mixed results in a variety of solid tumors. The reasons for response variability remain unknown, including the temporal and spatial patterns of receptor tyrosine kinase expression. Methods to detect and quantify the presence of such cellular receptors would greatly facilitate drug development and therapy response assessment. We aimed to generate specific imaging agents as potential companion diagnostics that could also be used for targeted radionuclide therapy. Here, we report on the synthesis and initial preclinical performance of (64)Cu-labeled probes that were based on the kinase inhibitor already in clinical use, vandetanib (ZD6474), as a VEGFR-selective theranostic radiopharmaceutical. A monomeric (ZD-G1) and a dimeric (ZD-G2) derivative of ZD6474 were synthesized and conjugated with DOTA for chelation with (64)Cu to produce the probes (64)Cu-DOTA-ZD-G1 and (64)Cu-DOTA-ZD-G2. The binding affinity and specificity to VEGFR were measured using U-87 MG cells known to overexpress VEGFR. Small-animal PET and biodistribution studies were performed with (64)Cu-labeled probes (3-4 MBq) intravenously administered in U-87 MG tumor-bearing mice with or without coinjection of unlabeled ZD-G2 for up to 24 h after injection. Receptor-binding assays yielded a mean equilibrium dissociation constant of 44.7 and 0.45 nM for monomeric and dimeric forms, respectively, indicating a synergistic effect in VEGFR affinity by multivalency. Small-animal PET/CT imaging showed rapid tumor accumulation of (64)Cu-DOTA-ZD-G2, with excellent tumor-to-normal tissue contrast by 24 h. Coinjection of the (64)Cu-DOTA-ZD-G2 with 50 nmol (60 μg) of nonradioactive ZD-G2 effectively blocked tumor uptake. A (64)Cu-labeled probe derived from an

  9. Preparation and preclinical evaluation of (66)Ga-DOTA-E(c(RGDfK))2 as a potential theranostic radiopharmaceutical.

    Science.gov (United States)

    Lopez-Rodriguez, V; Gaspar-Carcamo, R E; Pedraza-Lopez, M; Rojas-Calderon, E L; Arteaga de Murphy, C; Ferro-Flores, G; Avila-Rodriguez, M A

    2015-02-01

    Integrin αvβ3 plays an important role in angiogenesis and is over-expressed in tumoral endothelial cells and some other tumor cells. RGD (Arg-Gly-Asn) peptides labeled with (68)Ga (t1/2=68min) have showed good characteristics for imaging of αvβ3 expression using positron emission tomography (PET). Gallium-66 has been proposed as a PET imaging alternative to (68)Ga and given the unique high energy of its emitted positrons (Emax 4.15MeV) it may also be useful for therapy. The aim of this research is to prepare [(66)Ga]DOTA-E-[c(RGDfK)]2 and evaluate in mice its potential as a new theranostic radiopharmaceutical. High specific activity (66)Ga was produced via the (66)Zn(p,n) reaction, and the labelling method of DOTA-E-[c(RGDfK)]2 with (66)Ga was optimized. Radiochemical purity was determined by TLC, and in vitro stability and protein binding were determined. Serial microPET imaging and biodistribution studies were carried out in nude mice bearing C6 xenografts. Radiation absorbed dose estimates were based on the biodistribution studies, where tumor and organs of interest were collected at 0.5, 1, 3, 5 and 24h post-injection of [(66)Ga]DOTA-E-[c(RGDfK)]2. Our results have shown that [(66)Ga]DOTA-E-[c(RGDfK)]2 can be prepared with high radiochemical purity (>97%), specific activity (36-67GBq/μmol), in vitro stability, and moderate protein binding. MicroPET imaging up to 24 post-injection showed contrasting tumors reflecting αvβ3-targeted tracer accumulation. Biodistribution studies and dosimetry estimations showed a stable tumor uptake, rapid blood clearance, and favorable tumor-to-tissue ratios. The peptide conjugated DOTA-E-[c(RGDfK)]2 labeled with (66)Ga may be attractive as a theranostic agent for tumors over-expressing αvβ3 integrins. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Characterization of the anti tumoral activity of the thiosemicarbazones derived from N(4)-methyl-tolyl-2acetylpyridine And 2-pyridinoformamide and its metal complex: evaluation of the radiopharmaceutical potential; Caracterizacao da atividade antitumoral das tiossemicarbazonas derivadas de N(4)-metil-toluil-2-acetilpiridina e 2-piridinoformamida e seus complexos metalicos: avaliacao do potencial radiofarmaceutico

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Paulo Roberto Ornelas da

    2008-07-01

    Thiosemicarbazones have attracted great pharmacological interest because of their biological properties, such as cytotoxic activity against multiple strains of human tumors. The most studied compounds are pyridine-based because of their resemblance to pyridoxal metabolites that attach to co-enzyme B{sub 6}-dependant enzymes. This work aimed the characterization of the anti tumoral effect of N(4)-methyl-tolyl-2-acetylpyridine and 2-pyridinoformamide-derived thiosemicarbazones and the development of a radiopharmaceutical based on a thiosemicarbazone metal complex for positron emission tomography. In the first phase of this study were synthesized twenty-one thiosemicarbazones, derived from N(4)methyl-2 acetylpyridine and 2-pyridine formamide, as well as their metal complexes (Sn, Ga and Cu). Their cytotoxic potential were evaluated against brain and breast tumor cells in vitro. Our results showed all of them presented powerful cytotoxic and antiproliferative activities against glioblastoma multiform and breast adenocarcinoma at very low concentrations (nanomolar range). Morphological alterations characteristic of apoptosis, such as cell shrinkage, chromatin condensation were observed. Copper chloride was used as control and has presented IC50 at millimolar range suggesting that copper complexation with thiosemicarbazone significantly increases (more than 1 million) the anti tumoral effect of this metal. Due to the potent anti tumoral activity of N(4)-methyl-tolyl-2-acetylpyridine derived thiosemicarbazones and the excellent properties of {sup 64}Cu (T{sub 1/2} = 12.7 hours, {beta}{sup +}, {beta}{sup -}, and EC decay), at the second part for this work it was developed a new imaging agent (radiopharmaceutical) for tumor detection by positron emission tomography (PET). The radiopharmaceuticals were produced in the nuclear reactor TRIGA-IPR-R1 from CDTN, via neutron capture reaction {sup 63}Cu (n,{gamma}) {sup 64}Cu, of the copper complex N(4)-ortho-toluyl-2

  11. Paediatric radiopharmaceutical administration

    DEFF Research Database (Denmark)

    Lassmann, Michael; Treves, S Ted; Borgwardt, Lise

    2014-01-01

    In 2008 the EANM published their paediatric dosage card. In 2011 the North American consensus guidelines recommended a set of administered activities for paediatric nuclear medicine. During the EANM congress in 2012 a working group of the EANM and the SNMMI met to study the possibility of harmoni...

  12. Radiopharmaceuticals in Acute Porphyria

    NARCIS (Netherlands)

    Schreuder, Nanno; Mamedova, Ilahä; Jansman, Frank G A

    2016-01-01

    PURPOSE: The acute porphyrias are a group of rare metabolic disorders of the heme biosynthetic pathway. Carriers of the acute porphyria gene are prone to potentially fatal acute attacks, which can be precipitated by drug exposure. It is therefore important to know whether a drug is safe for carriers

  13. Determination of radiochemistry purity and pH of radiopharmaceutical in Northeast nuclear medicine services; Determinacao da pureza radioquimica e pH de radiofarmacos em servicos de medicina nuclear do Nordeste

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Wellington; Santos, Poliane, E-mail: wellington.gandrade@gmail.com, E-mail: polianeangelo@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Lima, Fernando de Andrade; Lima, Fabiana Farias de, E-mail: falima@cnen.gov.br, E-mail: ffmima@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2013-07-01

    The radiopharmaceutical is a chemical compound associated with a radionuclide, which is selected so that meets the need cf diagnosis and capable of producing quality images. Drugs labeled with {sup 99m}Tc radionuclide kits consist of lyophilized, and be handled by the nuclear medicine services (NMS) must pass tests as the resolution of ANVISA (RDC 38) published in 2008. Among these tests are those of radiochemical purity and pH determination. This study evaluated the radiochemical purity of radiopharmaceuticals and pH SMN manipulated in the Northeast. The radiochemical purity (RCP) was determined by thin layer chromatography, which were used Whatman Registered-Sign and silica gel, with dimensions of 1 x 10 cm, as stationary phase, and solvents indicated in the inserts of manufacturers. The chromatographic strips were placed in sealed containers so as not to touch the walls thereof. After the chromatographic run, the tape was cut every centimeter and the activities determined in doses of each calibrator NMS. The pH of the radiopharmaceutical was assessed through the use of universal pH paper (Merck Registered-Sign ) and obtained staining compared with its color scale. The results showed (hat 82.6% and 100% of the radiopharmaceuticals of the samples were within the limits recommended by international pharmacopoeias for radiochemical purity and pl-l, respectively. There is then the need to include in routine tests indicated SMN by ANVISA. Well, they can detect possible problems in the marking of radiopharmaceuticals administered to the patient and avoid inappropriate material. (author)

  14. Survey or quality for radiopharmaceuticals and activimeters available in services of nuclear medicine from Recife, Pernambuco State, Brazil; Estudo da qualidade dos radiofarmacos e dos activimetros utilizados nos servicos de medicina nuclear do Recife

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Fernanda Maria Dornellas Camara

    2001-08-01

    The radiopharmaceutical used in Nuclear Medicine must present high chemical and radiochemical purities in order to obtain images with contrast and clearness adequate for the diagnosis. Test should be made by the Nuclear Medicine institutes to evaluate the presence of molybdenum, aluminium and the free Tc O{sub 4}{sup -}/TC-HR in the radiopharmaceutical before they use it. On the other hand, the activity to be administered to the patient is determined by the activimeters available in the Nuclear Medicine institutions. So it is necessary to perform tests to verify operating conditions of the activimeter to guarantee that the dose received by patient is the prescribed by the physician. In Brazil, few clinics of Nuclear Medicine are implanting the tests of the radiopharmaceutical and of the activimeters. The objective of this work is to establish the procedures for the radiopharmaceutical tests and to evaluate the quality of the radiopharmaceutical used at the clinics of Recife, as well as the operation conditions of the activemeters in these institutions. The results show that all the activimeters analyzed present a good performance and that the equipment with Geiger-Muller detectors present larger instability than the ones that use ionization chamber. Concerning the Mo/Tc generators, it was observed that only one presented Mo in the generator eluate with concentration over the acceptable limits and that the concentration of Al found in the samples analyzed were below the limits. On the other hand, in 73% of the MIBI analyzed samples were observed problems with its preparation that were caused by the procedures adopted at the clinics, which do not follow the manufacturers recommendations. (author)

  15. Formulation of an inhibitor radiopharmaceutical of prostatic antigen of {sup 177}Lu-Glu-Nh-CO-Nh-Lys membrane; Formulacion de un radiofarmaco inhibidor del antigeno prostatico de membrana {sup 177}Lu-Glu-NH-CO-NH-Lys

    Energy Technology Data Exchange (ETDEWEB)

    Ortega S, D.

    2015-07-01

    The prostate specific membrane antigen (PSMA) is a zinc metalloenzyme that is expressed on the cell membrane and highly expressed in prostate cancer. Recently, it has been demonstrated that the peptide sequence Glu-Nh-CO-Nh-Lys inhibit PSMA activity through an electrostatic interaction with the Zn. Several theragnostic radiopharmaceuticals with base in {sup 177}Lu have been developed for radiotherapy of specific molecular targets because gamma and beta emissions of the radionuclide (β = 0.498 MeV and γ= 0.133 MeV). However, there is currently no label a formulation for preparing a radiopharmaceutical of {sup 177}Lu-Glu-Nh-CO-Nh-Lys useful treatment of prostate cancer. The aim of this research was to optimize and document the process of production of the radiopharmaceutical {sup 177}Lu-Glu-Nh-CO-Nh-Lys for sanitary registration application before the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). The optimization of the production process was assessed a factorial design of three variables with mixed levels (3 x 3 x 2) where the dependent variable is the radiochemical purity, the analytical method was validated by UV-Vis spectrophotometry. Next, process validation was carried out by labeling 3 lots of the optimized formulation of the radiopharmaceutical (5.55 GBq (2.16 μg) of {sup 177}LuCl{sub 3}, 90 mg peptide PSMA, 50 mg ascorbic acid and 150 μL of acetate buffer 1 M ph 5), long-term stability was performed by high resolution liquid chromatography) to determine its useful shelf life. 3 validation batches were prepared under protocols of Good Manufacturing Practice (GMP) in the Production Plant of Radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ), meet specifications preset by obtaining a sterile and free development of bacterial endotoxin yields of labeled 100% and which retains its quality characteristics radiochemical purity greater than 90% for at least 15 days. (Author)

  16. Determination of bacterial endotoxin (pyrogen) in radiopharmaceuticals by the gel clot method. Validation; Determinacao de endotoxina bacteriana (pirogenio) em radiofarmacos pelo metodo de formacao de gel. Validacao

    Energy Technology Data Exchange (ETDEWEB)

    Fukumori, Neuza Taeko Okasaki

    2008-07-01

    Before the Limulus amebocyte lysate (LAL) test, the only available means of pirogenicity testing for parenteral drugs and medical devices was the United States Pharmacopoeia (USP) rabbit pyrogen test. Especially for radiopharmaceuticals, the LAL assay is the elective way to determine bacterial endotoxin. The aim of this work was to validate the gel clot method for some radiopharmaceuticals without measurable interference. The FDA's LALTest guideline defines interference as a condition that causes a significant difference between the endpoints of a positive water control and positive product control series using a standard endotoxin. Experiments were performed in accordance to the USP bacterial endotoxins test in the {sup 131}I- m-iodobenzylguanidine; the radioisotopes Gallium-67 and Thallium-201; the lyophilized reagents DTPA, Phytate, GHA, HSA and Colloidal Tin. The Maximum Valid Dilution (MVD) was calculated for each product based upon the clinical dose of the material and a twofold serial dilution below the MVD was performed in duplicate to detect interferences. The labeled sensitivity of the used LAL reagent was 0.125 EU mL{sup -1} (Endotoxin Units per milliliter). For validation, a dilution series was performed, a twofold dilution of control standard endotoxin (CSE) from 0.5 to 0.03 EU mL{sup -1}, to confirm the labeled sensitivity of the LAL reagent being tested in sterile and non pyrogenic water, in quadruplicate. The same dilution series was performed with the CSE and the product in the 1:100 dilution factor, in three consecutive batches of each radiopharmaceutical. The products {sup 131}I-m-iodobenzylguanidine, Gallium-67, Thallium-201, DTPA, HSA and Colloidal Tin were found compatible with the LAL test at a 1:100 dilution factor. Phytate and GHA showed some interference in the gel clot test. Other techniques to determine endotoxins as the chromogenic (color development) and the turbidimetric test (turbidity development), were also assessed to get

  17. A PET-compatible tissue bioreactor for research, discovery, and validation of imaging biomarkers and radiopharmaceuticals: system design and proof-of-concept studies.

    Science.gov (United States)

    Whitehead, Timothy D; Nemanich, Samuel T; Dence, Carmen; Shoghi, Kooresh I

    2013-10-01

    Research and discovery of novel radiopharmaceuticals and targets thereof generally involves initial studies in cell cultures, followed by animal studies, both of which present several inherent limitations. The objective of this work was to develop a tissue bioreactor (TBR) enabling modulation of the microenvironment and to integrate the TBR with a small-animal PET scanner to facilitate imaging biomarker research and discovery and validation of radiopharmaceuticals. The TBR chamber is a custom-blown, water-jacketed, glass vessel enclosed in a circulating perfusion bath powered by a peristaltic pump, which is integrated within the field of view of the PET scanner. The chamber is in series with a gas exchanger and a vessel for degassing the system during filling. Dissolved oxygen/temperature probes and septa for injection or sampling are located at the inlet and outlet of the cell chamber. A pH probe is located at the chamber outlet. Effluent is collected in the fraction collector as mixed-cup samples. In addition, both medium and tissue chamber can be sampled to investigate tissue and secretory products through multiscale analysis. As a proof of concept, we studied the effects of lipids on glucose uptake using HepG2 cells. To that end, we varied the nutrient substrate environment over a period of approximately 27 d, before and after the addition of lipids, and studied the effects of pioglitazone, a peroxisome proliferator-activated receptor γ agonist, on lipid and glucose uptake. In parallel, the TBR was imaged by PET in conjunction with (11)C-palmitate in the presence and absence of lipids to characterize (11)C-palmitate uptake. The O2 consumption, glucose consumption, lactate production, and free fatty acid consumption and production rates were consistent in demonstrating the effects of lipids on glucose uptake. Pioglitazone exhibited improved glucose uptake within 3 d of treatment. Semiquantitative analysis suggested that lipids induced greater (11)C

  18. Rhenium-188 and technetium-99m nitridobis(N-ethoxy-N-ethyldithiocarbamate) leucocyte labelling radiopharmaceuticals: [{sup 188}ReN(NOET){sub 2}] and [{sup 99m}TcN(NOET){sub 2}], NOET Et(EtO)NCS{sub 2}: Their in vitro localization and chemical behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Demaimay, Florian; Dazord, Leontine; Roucoux, Alain; Noiret, Nicolas; Patin, Henri; Moisan, Annick

    1997-11-01

    In this study, we have investigated the preparation of rhenium-188 nitridobis(N-ethoxy-N-ethyldithiocarbamate) [{sup 188}ReN(NOET){sub 2}] (NOET Et(EtO)NCS{sub 2}), analogous to the known technetium-99m radiopharmaceutical. The new {sup 188}Re complex was synthesized in good yield with a satisfactory radiochemical purity, using a kit method. The subcellular localization of both radiopharmaceuticals in granulocytes was observed by microautoradiography. The uptake was independent of the radionuclide and predominantly nuclear. Furthermore, HPLC was used to characterize the {sup 99m}Tc complex before and after blood cell labelling and revealed that the intact radiopharmaceutical was involved.

  19. Radiation protection optimization in practices for radiopharmaceuticals production at IEN; Otimizacao da protecao radiologica nas praticas para a producao de radiofarmaco no IEN

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Osvaldir Paulo dos

    2004-06-15

    This works has arisen from the need of updating radiological protection procedures, creating new ones and training qualified personnel to perform radiological protection duties in a nuclear facility. The main purpose of the research was to assess and minimize gamma and neutron dose rates emitted during the production and handling of radiopharmaceuticals at IEN/DIRA. A mobile measurements system (SMMG-N) was developed for on-site measurements. This system has proven to be more handy than the equipment formerly used for for this task. It has also proven to reduce the measurements uncertainties and to allow for the standardization of assessment procedures. He dose rates calculated using the data provided by this system have been compared with results obtained otherwise and good agreement was observed between them. This study has confirmed the need to improve the radiation shielding of KIPROS target-chamber and target vault in order to meet the radiological principles of dose rate limitation and optimization. (author)

  20. Preparation of the radiopharmaceutical {sup 99m} Tc-HYNIC-[Lys{sup 3}]-BN; Preparacion del radiofarmaco {sup 99m} Tc-HYNIC-[Lys{sup 3}]-BN

    Energy Technology Data Exchange (ETDEWEB)

    Conde S, E. [Universidad Autonoma del Estado de Mexico, Facultad de Quimica, 50000 Toluca, Estado de Mexico (Mexico)

    2007-07-01

    In accordance with their design, the radiopharmaceuticals can be divided in three generations. The radiopharmaceuticals of third generation are used in nuclear medicine to obtain images of specific molecular targets, and they are only in their capacity to detect in vivo such specific biochemical places as receivers and enzymes. The receivers of regulator peptides are over expressed in numerous carcinogenic cells. Those receivers have been used as molecular targets of radiolabelled peptides to locate cancerous tumors. The small peptide bombesin (BN, 14 amino acids) it was isolated of the frog skin and it belongs to a wide neuropeptides group with many biological functions. The equivalent human is the liberator peptide of the gastrin (GRP, 27 amino acids) and his receivers (r-GRP) that are on expressed in the membranes of the tumor cells. The receiving subtype 2 of bombesin (receiving GRP) it is on expressed in several human tumors including breast, prostate, lung cells and pancreatic cancer. Some radiopharmaceuticals similar of BN has been developed that were prepared to be used in nuclear medicine for the detection of wicked tumors and to evidence prostate cancers, breast and of lymphatic nodules. A technique was developed to allow the conjugation of HYNIC-[Lys3]-BN that allowed to obtain this product with a high purity. The identity was determined by HPLC chromatography. It was necessary the validation of the method and the HPLC system, to assure that the results were reliable. Linearity, specificity, accuracy and precision parameters were analyzed, that are those required by the Mexican pharmacopoeia for chromatographic methods. With this conjugated a formulation for lyophilized kits were analyzed, with the purpose of obtaining a radiochemical purity, after the labelled one with {sup 99m}Tc, bigger to 95%; the components used in the nucleus-equipment should favor the conjugation of the {sup 99m}Tc by means of a ligands exchange between the tricine and the

  1. Formulation, radiopharmaceutical kinetics and dosimetry of the {sup 188}Re(V)-DMSA complex; Formulacion, radiofarmacocinetica y dosimetria del complejo {sup 188}Re(V)-DMSA

    Energy Technology Data Exchange (ETDEWEB)

    Garcia S, L.; Ferro F, G. [Departamento de Materiales Radiactivos. Instituto Nacional de Investigaciones Nucleares, C.P. 52045 Salazar, Estado de Mexico (Mexico); Murphy, C.A. de; Pedraza L, M. [Departamento de Medicina Nuclear, Instituto Nacional de la Nutricion, Salvador Zubiran, Mexico D.F. (Mexico); Azorin N, J. [Departamento de Fisica, Universidad Autonoma Metropolitana Iztapalapa, Mexico D.F. (Mexico)

    1999-07-01

    It was developed through experimental design (ANOVA), a formulation to prepare the {sup 188} Re(V)-Dmsa complex. Likewise, there were realized studies of radiopharmaceutical kinetics and internal dosimetry in animals, its normal and with induced tumors, considering an open bi compartmental model using the MIRD methodology. The {sup 188} Re(V)-Dmsa complex was obtained with a radiochemical purity greater than 95% incubating 30 min at 90 Centigrade under the following formulation: [SnCl{sub 2}] = 1.4 mg/ml, [ascorbic acid] = 0.5 mg/ml, p H = 2.0 - 3.0. The stability test of the formulation, shows that after 48 h of its preparation, does not produce radiolytic degradation neither chemical decomposition. The radiopharmaceutical kinetics data show an average residence time 7.2h, velocity constant {alpha} = 0.6508h{sup -1} and {beta} = 0.1046 h{sup -1} with an apparent distribution volume 6.9 l. The main elimination via was renal and it was observed osseous caption with an accumulated activity 522.049 {+-} 62 MBq h (residence time 14.1094 {+-} 1.69h). In according with the dosimetric calculations, by each 37 MBq injected, the equivalent dose at the tumor was 9.67{+-} 0.33 Sv/g, for an effective dose 0.292 {+-} 0.0017 mSv/MBq. The images obtained in the gamma camera of the mice with induced tumors, show that do not have significant accumulation in the metabolic organs. The caption in bone and in tumors induced of the {sup 188} Re(V)-Dmsa complex, show its potential for be used as a palliative agent for pain in patients with osseous metastasis and in the treatment of tumors of soft tissue. (Author)

  2. Modular syntheses of H₄octapa and H₂dedpa, and yttrium coordination chemistry relevant to ⁸⁶Y/⁹⁰Y radiopharmaceuticals.

    Science.gov (United States)

    Price, Eric W; Cawthray, Jacqueline F; Adam, Michael J; Orvig, Chris

    2014-05-21

    The ligands H2dedpa, H4octapa, p-SCN-Bn-H2dedpa, and p-SCN-Bn-H4octapa were synthesized using a new protection chemistry approach, with labile tert-butyl esters replacing the previously used methyl esters as protecting groups for picolinic acid moieties. Additionally, the ligands H2dedpa and p-SCN-Bn-H2dedpa were synthesized using nosyl protection chemistry for the first time. The use of tert-butyl esters allows for deprotection at room temperature in trifluoroacetic acid (TFA), which compares favorably to the harsh conditions of refluxing HCl (6 M) or LiOH that were previously required for methyl ester cleavage. H4octapa has recently been shown to be a very promising (111)In and (177)Lu ligand for radiopharmaceutical applications; therefore, coordination chemistry studies with Y(3+) are described to assess its potential for use with (86)Y/(90)Y. The solution chemistry of H4octapa with Y(3+) is shown to be suitable via solution NMR studies of the [Y(octapa)](-) complex and density functional theory (DFT) calculations of the predicted structure, suggesting properties similar to those of the analogous In(3+) and Lu(3+) complexes. The molecular electrostatic potential (MEP) was mapped onto the molecular surface of the DFT-calculated coordination structures, suggesting very similar and even charge distributions between both the Lu(3+) and Y(3+) complexes of octapa(4-), and coordinate structures between 8 (ligand only) and 9 (ligand and one H2O). Potentiometric titrations determined H4octapa to have a formation constant (log K(ML)) with Y(3+) of 18.3 ± 0.1, revealing high thermodynamic stability. This preliminary work suggests that H4octapa may be a competent ligand for future (86)Y/(90)Y radiopharmaceutical applications.

  3. Demand of radiopharmaceutical Fluoride 18-FDG (fluorodeoxyglucose) in the Sao Paulo State metropolitan area; Demanda do radiofarmaco fluor 18-FDG nas regioes metropolitanas do Estado de Sao Paulo

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Renato C.; Zouain, Desiree M. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Diretoria de Planejamento e Inovacao Tecnologica]. E-mail: renato.sato@uol.com.br; dmzouain@ipen.br

    2005-07-01

    This research presents partial results from the development of a Masters Dissertation for the Post-Graduation in Nuclear Technology Program - IPEN/USP, aiming to study the demand of radiopharmaceutical Fluoride 18-FDG (fluorodeoxyglucose) in the Sao Paulo State metropolitan area, as a subsidiary for the establishment of distribution strategy within the State. This study presented the results of a bibliographic review as well as the market evolution for FDG in Sao Paulo. Studies pointed to a tendency of an increase in the international and national nuclear medicine market; while the United States of America participate in 47% of the world profit, South America shares only 2.5% of the global market. This market will tend to grow in 2006 to 2020 up to 776% for diagnosis and 760% for therapy. Partial results are presented in this study from researching medical centers that use PET in the city of Sao Paulo, as well as companies that commercialize the equipment and the manufacturer center. There is an increase of sales for IPEN's Fluoride 18-FDG and its representation on the total radiopharmaceutical profit surpassed 5.3% in 2003 to 8.2% in 2004. The dissemination of this technology in Brazil is lately being discussed especially due to the acquisition price of the equipment as well as the viability of the resources (Fluoride 18- FDG; implementation strategies of regional cyclotron accelerators) and the question of remuneration of the PET produced exams for health care plans and national health care system (SUS). IPEN is developing yet another study to grasp possible demand for this product in the Southern and Southeastern regions, allowing better view of the necessity of the supplement, and in study the implementation of a new cyclotron in the institute dedicated for the production of Fluoride 18-FDG. (author)

  4. Development of an injectable formulation for the preparation of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin; Desarrollo de una formulacion inyectable para la preparacion del radiofarmaco {sup 68}Ga-DOTA-Sargastrina

    Energy Technology Data Exchange (ETDEWEB)

    Castillo P, M.

    2015-07-01

    The CCK2 receptor (cholecystokinin) is located in areas of the central and peripheral nervous system and is over expressed in several types of human cancer, as medullar thyroid, lung and ovarian carcinomas. One of the endogenous ligands for the CCK2 receptor is the gastrin, so that radiolabeled peptides analogues to gastrin as Sar gastrin (Gln-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH{sub 2}) have been proposed as potential diagnostic radiopharmaceuticals for obtaining tumors images with CCK2 receptors over expressed. The {sup 68}Ga is an ideal candidate for the peptides radiolabelled and has favorable characteristics to be used for diagnostic purposes by imaging with Positron emission tomography (PET). This work aimed to verify the technical documentation of the production process of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin for its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS) in Mexico. For optimization of the production process was assessed a factorial design of two variables with mixed levels (27 combinations), where the dependent variable was the radiochemical purity. The analytical method used for evaluating the content of Sar gastrin peptide in the injectable formulation was also validated by High-performance liquid chromatography. Subsequently the validation of the production process was carried out by manufacturing of lots in single-dose of the optimized injectable formulation of the radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin and the stability study was conducted at different times to determine the useful life time. The following was established as the optimal pharmaceutical formulation: 185 MBq of {sup 68}Ga, 50 μg de DOTA-Sar gastrin, 14 mg of sodium acetate and 0.5 m L of buffer acetates, 1.0 M, ph 4.22 in 2.5 m L of the vehicle. The analytical method used to determine the radiochemical purity of the formulation satisfied the requirements for the intended analytical

  5. In vivo and in vitro study of the 9{sup 9mT}c-DMSA radiopharmaceutical connection to blood elements; Estudo in vivo e in vitro da ligacao do radiofarmaco 99mTc-DMSA aos elementos sanquineos

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, Rosimeire de S. [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria]|[Hospital Universitario Clementino Fraga Filho, Rio de Janeiro (Brazil); Gomes, Maria L.; Mattos, Deise M.M.; Moreno, Silvana R.F.; Dire, Glaucio F.; Lima, Elaine A.; Lima-Filho, Guilherme L.; Aleixo, Luiz Claudio [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Bernardo-Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria]|[Instituto Nacional do Cancer, Rio de Janeiro (Brazil). Centro de Pesquisa Basica] E-mail: rosfreitas@hotmail.com

    2002-07-01

    Radiopharmaceuticals are widely used in nuclear medicine. The comprehension of their uptake mechanism in target organs, as well as their clearance may depend on the elucidation of their biochemical characteristics, for instance, their binding to blood elements. The reported precipitating studies of blood with radiopharmaceuticals have shown that the results can not be easily compared. Then, we decide evaluate of the binding proteins on the blood elements using trichloroacetic acid (TCA) to determine the radioactivity of the dimercaptosuccinic acid with technetium-99m (99mTc-DMSA) present in precipitating plasma (P) and blood cells (BC). Depending on the TCA concentration we have determined different values in the insoluble fractions of the plasma when the in vivo and in vitro evaluations were carried out. (author)

  6. A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with (223)Ra-, (131)I-, (177)Lu- and (111)In-labelled radiopharmaceuticals.

    Science.gov (United States)

    Amato, Ernesto; Leotta, Salvatore; Italiano, Antonio; Baldari, Sergio

    2015-07-01

    The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature. We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered. Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For (223)Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions. Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  7. Alguns aspectos sobre geradores e radiofármacos de tecnécio-99m e seus controles de qualidade Technetium-99m generators and radiopharmaceuticals and quality control tests.

    Directory of Open Access Journals (Sweden)

    Fabio Luiz Navarro Marques

    2001-08-01

    Full Text Available Radiofármacos marcados com tecnécio-99m são os principais agentes para diagnósticos utilizados nas clínicas de medicina nuclear, em função de uma série de características físicas do radionuclídeo e pela praticidade dos radiofármacos serem preparados no local de uso, por meio de uma reação de complexação entre um agente complexante (fármaco e o tecnécio-99m. Entretanto, durante esta reação podem ser geradas algumas impurezas que proporcionam a formação de produtos com baixa qualidade ou com características diferentes das desejadas. No presente trabalho serão apresentados alguns dos fatores que podem interferir na qualidade dos radiofármacos e os controles que podem ser utilizados para garantir sua qualidade.Technetium-99m labeled radiopharmaceuticals are currently the main diagnostic agents used in nuclear medicine. Radiopharmaceuticals are prepared locally through a reaction between a complexant agent (pharmaceutical and technetium-99m. These reactions may generate impurities resulting into the production of radiopharmaceuticals with substandard quality or with different characteristics from those considered ideal. In this article we discuss some of the factors that may interfere with the preparation of radiopharmaceuticals and the quality control tests that can be used to ensure the quality of the agents.

  8. Convenient and Efficient Method for Quality Control Analysis of 18F-Fluorocholine: For a Small Scale GMP-based Radiopharmaceuticals Laboratory Set-up.

    Science.gov (United States)

    Hassan, Hishar; Abu Bakar, Suharzelim; Halim, Khairul Najah Che A; Idris, Jaleezah; Nordin, Abdul Jalil

    2016-01-01

    Prostate cancer continues to be the most prevalent cancer in men in Malaysia. As time progresses, the prospect of PET imaging modality in diagnosis of prostate cancer is promising, with on-going improvement on novel tracers. Among all tracers, 18F-Fluorocholine is reported to be a reputable tracer and reliable diagnostic technique for prostate imaging. Nonetheless, only 18F-Fluorodeoxyglucose (18F-FDG) is available and used in most oncology cases in Malaysia. With a small scale GMP-based radiopharmaceuticals laboratory set-up, initial efforts have been taken to put Malaysia on 18F-Fluorocholine map. This article presents a convenient, efficient and reliable method for quality control analysis of 18F-Fluorocholine. Besides, the aim of this research work is to assist local GMP radiopharmaceuticals laboratories and local authority in Malaysia for quality control analysis of 18F-Fluorocholine guideline. In this study, prior to synthesis, quality control analysis method for 18F-Fluorocholine was developed and validated, by adapting the equipment set-up used in 18F-Fluorodeoxyglucose (18FFDG) routine production. Quality control on the 18F-Fluorocholine was performed by means of pH, radionuclidic identity, radio-high performance liquid chromatography equipped with ultraviolet, radio- thin layer chromatography, gas chromatography and filter integrity test. Post-synthesis; the pH of 18F-Fluorocholine was 6.42 ± 0.04, with half-life of 109.5 minutes (n = 12). The radiochemical purity was consistently higher than 99%, both in radio-high performance liquid chromatography equipped with ultraviolet (r-HPLC; SCX column, 0.25 M NaH2PO4: acetonitrile) and radio-thin layer chromatography method (r-TLC). The calculated relative retention time (RRT) in r-HPLC was 1.02, whereas the retention factor (Rf) in r-TLC was 0.64. Potential impurities from 18F-Fluorocholine synthesis such as ethanol, acetonitrile, dimethylethanolamine and dibromomethane were determined in gas chromatography

  9. PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals.

    Science.gov (United States)

    Boschi, Alessandra; Massi, Alessandro; Uccelli, Licia; Pasquali, Micol; Duatti, Adriano

    2010-11-01

    A novel nitrido nitrogen atom donor for the preparation of (99m)Tc and (188)Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO(2)C-PEG(600)-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H(2)N-N(CH(3))-C(S)SCH(3), HDTCZ] with polyethylene glycol 600 (PEG(600)). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)](0/+) (M=(99m)Tc, (188)Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H(2)OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L)(2)] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [M≡N](2+) core, through reduction of generator-eluted (99m)Tc-pertechnetate or (188)Re-perrhenate with thin (II) chloride in the presence of HO(2)C-PEG(600)-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ did not show coordinating properties toward the M≡N ((99m)Tc, (188)Re) core. Biodistribution studies in rats of the hitherto unreported [(99m)Tc(N)(PNP(3))DTCZ](+) and [(99m)Tc(N)(PNP(5))DTCZ](+) complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically increased in the interval between 60 and 120 min postinjection. Hence, the combination of the favourable chemical and biological properties of HO(2)C-PEG(600)-DTCZ

  10. H2CHXdedpa and H4CHXoctapa-chiral acyclic chelating ligands for (67/68)Ga and (111)In radiopharmaceuticals.

    Science.gov (United States)

    Ramogida, Caterina F; Cawthray, Jacqueline F; Boros, Eszter; Ferreira, Cara L; Patrick, Brian O; Adam, Michael J; Orvig, Chris

    2015-02-16

    The chiral acyclic ligands H2CHXdedpa (N4O2), H2CHXdedpa-bb (N4O2), and H4CHXoctapa (N4O4) (CHX = cyclohexyl/cyclohexane, H2dedpa = 1,2-[[6-carboxy-pyridin-2-yl]-methylamino]ethane, bb = N,N'-dibenzylated, H4octapa = N,N'-bis(6-carboxy-2-pyridylmethyl)-ethylenediamine-N,N'-diacetic acid) were synthesized, complexed with Ga(III) and/or In(III), and evaluated for their potential as chelating agents in radiopharmaceutical applications. The ligands were compared to the previously studied hexadentate H2dedpa and octadentate H4octapa ligands to determine the effect adding a chiral 1R,2R-trans-cyclohexane to replace the ethylenediamine backbone would have on metal complex stability and radiolabeling kinetics. It was found that [Ga(CHXdedpa)](+) showed very similar properties to those of [Ga(dedpa)](+), with only one isomer in solution observed by NMR spectroscopy, and minimal structural changes in the solid-state X-ray structure. Like [Ga(dedpa)](+), [Ga(CHXdedpa)](+) exhibited exceptionally high thermodynamic stability constants (log KML = 28.11(8)), and the chelate retained the ability to label (67)Ga quantitatively in 10 min at room temperature at ligand concentrations of 1 × 10(-5) M. In vitro kinetic inertness assays demonstrated the [(67)Ga(CHXdedpa)](+) complex to be more stable than [(67)Ga(dedpa)](+) in a human serum competition, with 90.5% and 77.8% of (67)Ga remaining chelate-bound after 2 h, respectively. Preliminary coordination studies of H4CHXoctapa with In(III) demonstrated [In(CHXoctapa)](-) to have an equivalently high thermodynamically stable constant as [In(octapa)](-), with log KML values of 27.16(9) and 26.76(14), respectively. The [(111)In(CHXoctapa)](-) complex showed exceptionally high in vitro kinetic inertness over 120 h in human serum, comparing well with previously reported [(111)In(octapa)](-) values, and an improved stability compared to the current industry "gold standards" 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA

  11. Development of additive [{sup 11}C]CO{sub 2} target system in the KOTRON-13 cyclotron and its application for [{sup 11}C]radiopharmaceutical production

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Byung Seok; Lee, Hong Jin [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 463-707 (Korea, Republic of); Lee, Won Kyung [Technical Support Team, Duchembio, Seoul 121-844 (Korea, Republic of); Hur, Min Goo; Yang, Seung Dae [Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Lee, Byung Chul, E-mail: leebc2001@gmail.com [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 463-707 (Korea, Republic of); Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 443-270 (Korea, Republic of); Kim, Sang Eun [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 463-707 (Korea, Republic of); Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 443-270 (Korea, Republic of); Smart Humanity Convergence Center, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 443-270 (Korea, Republic of)

    2015-08-01

    The KOTRON-13 cyclotron, which was developed in South Korea for the production of medical radioisotopes, has the structural limitation of only one beam-output port, restricting the production of the carbon-11 isotope. In the present study, we investigate the design of a switchable target system and develop an effective carbon-11 target in the KOTRON-13 cyclotron, for combination with the fluorine-18 target. The target system was designed by introducing a sliding-type element between the fluorine-18 and carbon-11 targets, a tailor-made C-11 target and its cooling system. For the efficient production of [{sup 11}C]CO{sub 2}, the desirable target shape and internal volume were determined by a Stopping and Range of Ions in Matter (SRIM) simulation program, and the target grid was modified to resist the cavity pressure during beam irradiation. We evaluated the [{sup 11}C]CO{sub 2} production while varying the material and thickness of the target foil, oxygen content of the nitrogen gas, and target loading pressure. Using sliding-type equipment including an additional gate valve and a high vacuum in a beam line, the bi-directional conversion between the fluorine-18 and carbon-11 targets was efficient regarding the accurate beam irradiation on both targets. The optimal [{sup 11}C]CO{sub 2} production for 30 min irradiation at 60 μA (86.6 ± 1.7 GBq in the target at EOB) was observed at a thickness of 19 μm with HAVAR® material as a target foil and a target loading pressure of 24 bar with nitrogen plus 300 ppb of oxygen gas. Additionally, the coolant cavity system in the target grid and target chamber is useful to remove the heat transferred to the target body by the internal convection of water and thereby ensure the stability of the [{sup 11}C]CO{sub 2} production under a high beam current. In the application of C-11 labeled radiopharmaceuticals such as [{sup 11}C]PIB, [{sup 11}C]DASB, [{sup 11}C]PBR28, [{sup 11}C]Methionine and [{sup 11}C]Clozapine, the radiochemical

  12. Preliminary studies on (177)Lu-labeled sodium pyrophosphate (177Lu-PYP) as a potential bone-seeking radiopharmaceutical for bone pain palliation.

    Science.gov (United States)

    Abbasi, Imtiaz Ahmed

    2012-08-01

    (99m)Tc-Sn-PYP (Technetium-99(m) labeled tin pyrophosphate) has been widely used as a radiopharmaceutical for bone scanning as well as in nuclear cardiology. It is also found in the body in trace amounts. (177)Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. PYP is an analogue of MDP and MDP has been labeled with (177)Lu. No study on preparing a complex of (177)Lu with PYP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking (177)Lu-PYP (Lutetium-177 labeled Pyrophosphate) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. (177)Lu was produced by irradiating lutetium foil (11 mg) natural target at a flux ∼1.0×10(14)n/cm(2)/s for 12 h in the swimming pool type reactor. (177)Lu in the form of (177)LuCl(3) was labeled with PYP. The radiochemical purity and labeling efficiencies were determined by paper chromatography. Labeling of (177)Lu with PYP was optimized and a labeled sample was subjected to HPLC analysis. To determine the charge on the (177)Lu-PYP complex, radio-electrophoresis was conducted for 1 h under a voltage of 300 V and 45 mA current using 0.025 M phosphate buffer (pH 6.9). Bioevaluation studies with rabbit under γ-camera were also performed to verify the skeletal uptake. The quality control using paper radio-chromatography has shown >99% radiochemical purity of (177)Lu-PYP complex. Radio-chromatography also showed maximum labeling at ligand/metal ratio=60:1. HPLC analysis showed 1.42±0.01 min retention time of (177)Lu-PYP complex. No decrease in labeling was observed at higher temperatures. Gamma-camera images of (177)Lu-PYP in normal rabbit at 24 h post injection also showed high skeletal uptake. The study demonstrated that sodium pyrophosphate could be labeled with (177)Lu with high radiochemical yields (>99%). Negatively charged (177)Lu-PYP complex retained stability for a day and at high

  13. Radiofarmácia e radiofármacos no Brasil: aspectos sanitários e fabris para a construção de uma linha de produção de radiofármacos PET Radiopharmacy and radiopharmaceuticals in Brazil: sanitaries aspects related to a project of an industry of PET radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Ralph Santos Oliveira

    2008-06-01

    Full Text Available O aumento do uso de radiofármacos PET (Pósitron Emission Tomography vem chamando a atenção dos profissionais da área de Medicina Nuclear e Farmácia, assim como das agências reguladoras. O objetivo é prover parâmetros estruturais e legais mínimos como uma referência nacional em radiofarmácia, que possam auxiliar as agências regulatórias, focando principalmente no projeto fabril.The increasing use of radiopharmaceuticals for PET (Positron Emission Tomography has come to the attention of nuclear medicine staff and regulatory bodies. The aim of this study is to provide a national reference in radiopharmacy that could help all nuclear medicine staff and specially the Brazilian's regulatory bodies focused on the industrial project.

  14. Development of more efficacious Tc-99m organ imaging agents for use in nuclear medicine by analytical characterization of radiopharmaceutical mixtures. Progress report, May 1, 1981-April 30, 1982

    Energy Technology Data Exchange (ETDEWEB)

    Heineman, W.R.; Deutsch, E.A.

    1981-12-01

    The objectives of this year's research were to develop a method for rapidly determining TcO/sub 4//sup -/ in /sup 99/Mo//sup 99m/Tc generator eluates, to improve the ability to chromatographically determine individual Tc-HEDP complexes in radiopharmaceuticals, and to investigate the effects of TcO/sub 4//sup -/ concentration and electrochemical reduction on the types and relative amounts of Tc-HEDP complexes present in a radiopharmaceutical formulation. A rapid and sensitive high performance liquid chromatographic (HPLC) method for the quantitative determination of pertechnetate (TcO/sub 4//sup -/) was developed. This HPLC-based analysis may be of considerable utility in assessing the history and function of /sup 99/MO/sup 99m/Tc generators as well as in the routine analysis of reduced technetium radiopharmaceuticals for the presence of undesired TcO/sub 4//sup -/. Encouraging results were obtained on a dimethyl amine column using aqueous (NH/sub 4/)/sub 2/SO/sub 4/ as the mobile phase. The preparation of Tc(NaBH/sub 4/) HEDP radiopharmaceutical analogues using varying concentrations of total TcO/sub 4//sup -/ shows a dramatic effect in the number and distribution of Tc-HEDP complexes over a TcO/sub 4//sup -/ concentration range of 10/sup -2/ to 10/sup -8/M. These results suggest that total TcO/sub 4//sup -/ concentration is an important parameter to be considered in the preparation of a specific Tc-HEDP complex to improve skeletal imaging. The preparation of Tc(electrode) HEDP radiopharmaceutical analogues by using electrochemical reduction was explored. The resulting solutions contain Tc-HEDP complexes that are tentatively identified as being the same complexes formed by NaBH/sub 4/ reduction, although the relative concentrations of these complexes are quite different with the two modes of reduction. Thus, electrochemical reduction shows promise as a viable route to the preparation of specific Tc-HEDP complexes for improved skeletal imaging.

  15. Motorcycle Parts

    Science.gov (United States)

    1993-01-01

    An article in NASA Tech Briefs describing a vacuum bagging process for forming composite parts helped a small Oklahoma Company to improve its manufacturing process. President of Performance Extremes, Larry Ortega, and his partners make motorcycle parts from carbon/epoxy to reduce weight. Using vacuum bags, parts have a better surface and fewer voids inside. When heat used in the vacuum bag process caused deformation upon cooling, a solution found in another tech brief solved the problem. A metal plate inside the vacuum bag made for more even heat transfer. A third article described a simple procedure for repairing loose connector pins, which the company has also utilized.

  16. A systematic study on the utility of CHX-A''-DTPA-NCS and NOTA-NCS as bifunctional chelators for177Lu radiopharmaceuticals.

    Science.gov (United States)

    Pandey, Usha; Gamre, Naresh; Lohar, Sharad Pandurang; Dash, Ashutosh

    2017-09-01

    This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for 177 Lu. While 177 Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of 177 Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of 177 Lu-NOTA-NCS significantly as compared to 177 Lu-CHX-A''-DTPA-NCS. In vitro stability of 177 Lu-CHX-A''-DTPA-NCS was also superior to 177 Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of 177 Lu radiopharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Study of the temperature distribution on welded thin plates of duplex steel to be used for the external clad of a cask for transportation of radiopharmaceuticals products

    Energy Technology Data Exchange (ETDEWEB)

    Betini, Evandro G.; Ceoni, Francisco C.; Mucsi, Cristiano S.; Politano, Rodolfo; Rossi, Jesualdo L., E-mail: egbetini@ipen.br, E-mail: fceoni@hotmail.com, E-mail: csmucsi@ipen.br, E-mail: politano@ipen.br, E-mail: jelrossi@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Orlando, Marcos T.D., E-mail: mtdorlando@gmail.com [Universidade Federal do Espirito Santo (CCE/DFIS/UFES), Vitoria, ES (Brazil). Centro de Ciencias Exatas. Departamento de Fisica

    2015-07-01

    The clad material for a proprietary transport device for radiopharmaceutical products is the main focus of the present work. The production of {sup 99}Mo-{sup 99m}Tc transport cask requires a receptacle or cask where the UNS S32304 duplex steel sheet has shown that it meets high demands as the required mechanical strength and the spread of impact or shock waves mitigation. This work reports the experimental efforts in recording the thermal distribution on autogenous thin plates of UNS S32304 steel during welding. The UNS S32304 duplex steel is the most probable candidate for the external clad of the containment package for the transport of radioactive substances so it is highly relevant the understanding of all its physical parameters and its behavior under the thermal cycle imposed by a welding process. For the welding of the UNS S32304 autogenous plates the GTAW (gas tungsten arc welding) process was used with a pure argon arc protection atmosphere in order to simulate a butt joint weld on a thin duplex steel plate without filler metal. The thermal cycles were recorded by means of K-type thermocouples embedded by electrical spot welding near the weld region and connected to a multi-channel data acquisition system. The obtained results validate the reliability of the experimental apparatus for the future complete analysis of the welding experiment and further comparison to numerical analysis. (author)

  18. A comparative analysis of pharmacokinetics properties of diagnostic bone-seeking radiopharmaceuticals on the basis of phosphonic acids and technetium-99m

    Science.gov (United States)

    Tishchenko, V. K.; Petriev, V. M.; Smoryzanova, O. A.; Zavestovskaya, I. N.

    2017-01-01

    This work is devoted to comparative research of pharmacokinetics properties of four bone-seeking radiopharmaceuticals (RPP) on the basis of bi- tetra- and penta-phosphonic acids. Biodistribution studies were performed in intact rats after intravenous injections of 99mTc-hydroxyethylidenediphosphonic acid (99mTc-HEDP), 99mTc-oxabiphor (99mTc-OXB), 99mTc-ethylenediaminetetramethylenephosphonic acid (99mTc-EDTMP) or 99mTc-diethylenetriaminopentakis(methylphosphonic acid) (99mTc-PPA). In the structure of the HEDP contains two phosphonic groups, OENTMP and EDTMP - four phosphonic groups, PPA - five phosphonic groups. Radiochemical yield of labeled 99mTc HEDP, OENTMP, EDTMP, PPA is not less than 95%, the radiochemical impurities does not exceed 5%. The investigated compounds have high stability in vivo and selective accumulation in osseous tissue. The highest concentrations of labeled compounds is reached in 3-24 hours after their intravenous injections. The investigated compounds are rapidly excreted from blood and soft organs and tissues mainly through the urinary routes. So present study has showed that these RPP have properties, which making them promising candidates as a diagnostic pharmaceuticals of bone metastases.

  19. The concept of minimum detectable activity of radionuclide activity meters and their suitability for routine quality control of radiopharmaceuticals. An experimental study.

    Science.gov (United States)

    Zagni, F; Cesarini, F; Lucconi, G; Cicoria, G; Pancaldi, D; Infantino, A; Vichi, S; Marengo, M

    2016-07-01

    Radionuclide activity meters ("dose calibrators") are ionization chambers designed to measure relatively high amount of activities which are normally contained in radiopharmaceuticals. However, in the current radiopharmacy practice, these radiation detectors have been proposed to be used in measurements of samples with lower activity, such as in routine quality control (QC) tests. To check the feasibility of such measurements, in this work we assessed the performance of four different devices in the lower range of detectability, by means of experimental measurements of a radioactive sample. Accuracy and precision of each device was evaluated as a function of the activity contained in the sample in order to estimate a threshold value, or minimum detectable activity (MDA), which, according to our operational definition, may be used to express the concept of Limit of Quantification (LoQ). Moreover, a generalized procedure for the estimation of the MDA was established, which, being device- and radionuclide-independent, it may be adopted by every laboratory. Our results showed a significant variability in the MDA achieved by different activity meters. Hence a single QC test may result feasible with one specific instrument, and not with another one. Moreover, feasibility depends also on the confidence level required for each test. For these reasons, each activity meter should be qualified for its MDA or LoQ by each laboratory according to a procedure such as that described in this paper. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The first experience of using 99mTc-Al2O3-based radiopharmaceutical for the detection of sentinel lymph nodes in cervical cancer patients

    Science.gov (United States)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-08-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3-based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (T1aNxMx-T2bNxMx) treated at the Tomsk Cancer Research Institute. In the 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 in peritumoral injected, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3 (the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac (14%), obturator (14%), presacral and retrosacral regions (14%), and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  1. Tumoral fibrosis effect on the radiation absorbed dose of {sup 177}Lu-Tyr{sup 3}-octreotate-gold nanoparticles and {sup 177}Lu-Tyr{sup 3}-octreotate radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Zambrano R, O. D.

    2015-07-01

    In this work was comparatively evaluated the effect of tumoral fibrosis in the radiation absorbed dose of the radiopharmaceutical {sup 177}Lu-Tyr{sup 3}-octreotate with and without gold nanoparticles. For this, was used an experimental array of tumoral fibrosis and computer models based on Monte Carlo calculations to simulate tumoral micro environments without fibrosis and with fibrosis. The computer simulation code Penelope (Penetration Energy Loss of Positron and Electrons) and MCNP (Monte Carlo N-particle Transport Code System) which are based on the Monte Carlo methodology were used to create the computer models for the simulation of the transport of particles (emitted by {sup 177}Lu) in the micro environments (without fibrosis and with fibrosis) with the purpose of calculating the radiation absorbed dose in the interstitial space and in the nucleus of cancer cells. The first computational model consisted of multiple concentric spheres (as onion shells) with the radioactive source homogeneously distributed in the shell between 5 and 10 μm in diameter which represents the internalization of the radioactive source into the cell cytoplasm as it occurs in target specific radiotherapy. The concentric spheres were useful to calculate the radiation absorbed dose in depth in the models without fibrosis and with fibrosis. Furthermore, there were constructed other computer models using two different codes that simulate the transport of radiation (Penelope and MCNP). These models consist of seven spheres that represent cancer cells (HeLa cells) of 10 μm in diameter and each one of them contain another smaller sphere in the center that represents the cell nucleus. A comparison was done of the radiation absorbed dose in the nucleus of the cells, calculated with both codes, Penelope and MCNP. The radioactive source ({sup 177}Lu) used for the simulations was given to the codes by means of a convoluted spectrum of the most important beta particles (high percentage emission

  2. Use of thin layer chromatography for the determination of radiochemical purity of radiopharmaceuticals in nuclear medicine services of Paraiba and Rio Grande do Norte, Brazil; Utilizacao da cromatografia em camada delgada para determinacao da pureza radioquimica de radiofarmacos em servicos de medicina nuclear da Paraiba e Rio Grande do Norte, Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, W.G.; Santos, P.A.L.; Lima, F.R.A. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Programa de Pos-Graduacao em Tecnologia Energetica; Lima, F.F., E-mail: wellington.gandrade@gmail.com [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2012-07-01

    The paper chromatography and the thin layer chromatography are separation techniques in which the radioactive components migrate because of their affinity with the eluent (mobile phase) or stationary phase, respectively. In radiopharmaceuticals labeled with {sup 99m}Tc, besides its own radiopharmaceutical, {sup 99m}TcO{sup 4-} free and TcO{sub 2} can be identified and quantified. The evaluation of radiochemical purity of radiopharmaceuticals is essential to produce images free of artifacts as well as avoid unnecessary absorbed dose to the patient. Once they are managed in humans it is important and necessary that they undergo to strict quality control. Because of this, ANVISA in its 'Resolucao da Diretoria Colegiada (RDC) 38 of June 4th, 2008 states the obligation of performing a minimum of tests in nuclear medicine services routine prior to human administration. This work evaluated, by the method of thin layer chromatography (TLC), radiochemical purity, determined the pH of the radiopharmaceutical DEXTRAN- 500, DMSA, DTPA, PHYTATE, MDP, MIBI and Sn-Col used in nuclear medicine services in the states of Paraiba and Rio Grande do Norte - Brazil. The results show that the use of thin layer chromatography (TLC) as a standard method in routine of nuclear medicine services is possible, because it provides important data for the evaluation of radiochemical purity, allowing the exclusion of a radiopharmaceutical poorly marked. (author)

  3. Part two

    DEFF Research Database (Denmark)

    Nielsen, Mads Pagh; Kær, Søren Knudsen; Korsgaard, Anders

    2008-01-01

    A novel micro combined heat and power system and a dynamic model thereof were presented in part one of the publication. In the following, the control system and dynamic performance of the system are presented. The model is subjected to a measured consumption pattern of 25 Danish single family hou...

  4. PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Boschi, Alessandra, E-mail: alessandra.boschi@unife.i [Laboratory of Nuclear Medicine, Department of Radiological Sciences, University of Ferrara, 44100 Ferrara (Italy); Massi, Alessandro [Department of Chemistry, University of Ferrara, 44100 Ferrara (Italy); Uccelli, Licia; Pasquali, Micol; Duatti, Adriano [Laboratory of Nuclear Medicine, Department of Radiological Sciences, University of Ferrara, 44100 Ferrara (Italy)

    2010-11-15

    A novel nitrido nitrogen atom donor for the preparation of {sup 99m}Tc and {sup 188}Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO{sub 2}C-PEG{sub 600}-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H{sub 2}N-N(CH{sub 3})-C({identical_to}S)SCH{sub 3}, HDTCZ] with polyethylene glycol 600 (PEG{sub 600}). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)]{sup 0/+} (M={sup 99m}Tc, {sup 188}Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H{sub 2}OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L){sub 2}] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO{sub 2}C-PEG{sub 600}-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [M{identical_to}N]{sup 2+} core, through reduction of generator-eluted {sup 99m}Tc-pertechnetate or {sup 188}Re-perrhenate with thin (II) chloride in the presence of HO{sub 2}C-PEG{sub 600}-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO{sub 2}C-PEG{sub 600}-DTCZ did not show coordinating properties toward the M{identical_to}N ({sup 99m}Tc, {sup 188}Re) core. Biodistribution studies in rats of the hitherto unreported [{sup 99m}Tc(N)(PNP{sub 3})DTCZ]{sup +} and [{sup 99m}Tc(N)(PNP{sub 5})DTCZ]{sup +} complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically

  5. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  6. Synthesis, labeling with {sup 99m}Tc and biokinetics of brains scintigraphy diaminodithiol perfusion radiopharmaceuticals; Sintese, marcacao com {sup 99m}Tc e biocinetica de radiofarmacos perfusorios diaminoditiolicos para cintilografias cerebrais

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, Marcos Moises

    1999-07-01

    The recent tomography status using radiopharmaceuticals have been contributing greatly with the 'age of certainty' in the diagnosis examination of syndromes, pathologies and clinical signs, because they can evidence some phenomena occurring in a molecular manner. The purpose of this work have had the development of new diaminodithiol (DADT) perfusion radiopharmaceuticals to be used in brain diagnosis using S.P.E.T. (Single Photon Emission Tomography). Initially, the rational planning had been performed with the new DADT molecular structures as radiopharmaceutical candidates. Using of Q.S.A.R. (Quantitative Structure Activity Relationship) techniques, the molecular descriptors such as partition coefficient and effective polarizability, have been studied in order to increase the blood brain barrier transport and the brain uptake respectively. Applying the Q.S.P.R. (Quantitative Structure Property Relationship) concepts to perform drug latentiation, based on bio-labile functional groups, the congener DADT derivative has been transformed into a pro-drug that works as a DADT moiety carrier, allowing the increasing of brain radiopharmaceutical uptake. Later on, synthetic routes and chemical purifications have been developed allowing the creation of the proposed chemical structure. Each new DADT derivative has been synthesized and analyzed in terms of elemental analysis, infrared and NMR spectra, in order to confirm its proposed chemical structure. Then, the new derivative has been labeled with {sup 99m}Tc, radiochemically purified, intravenously injected in Swiss mice, allowing its biodistribution to evidence its brain transport and uptake. The rational planning studies have been re-evaluated after each biodistribution had been performed, to see what kind of molecular descriptor was responsible for causing a stronger optimization in the brain perfusion characteristics and then, new DADT derivatives have been prepared. Three new DADT derivatives have been

  7. Kinetic and allometric models for dosimetry using radiopharmaceuticals labeled with lanthanides; Proposicao de modelos cineticos e alometricos para a dosimetria de radiofarmacos marcados com lantanideos

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina Ferreira

    2012-07-01

    This work proposes two models based in compartmental analyses: Animal model and Human model, using images from gamma camera measurements to determinate the kinetic constants of the {sup 177}Lu-DOTATATE to three animal species (rat Wistar, Armenian hamster and Syrian hamster) and to the human in biodistribution studies split in two phases: Phase 1 governed by uptake from the blood and Phase 2 governed by the real excretion. The kinetic constants obtained from the animals' data ere used to build allometric scaling to predict radiopharmaceutical biodistribution in the human employing relations by mass, metabolism, by life span and by physiological parameters. These extrapolation results were compared with the PRRT (Peptide receptor radiotherapy) patients kinetic data calculated using the Human model. The kinetic constants obtained from humans were used in dose assessment to PRRT patients considering MIRD 26 organs and tissues. Dosimetry results were in agreement with available results from literature. For the Phase 1 allometric scaling from kinetic data from the blood to the organs straight responsible for the {sup 177}Lu-DOTATATE metabolism and excretion - liver, kidneys and urinary bladder -show good correlation in the scaling by mass, metabolism and physiological and parameters. For the Phase 2, only the kinetic data from blood to the liver and to the kidneys show good correlation. Based in the anaesthetics inhibitory action over the renal excretion, there is not empirical basis to allow measurement times over 40 minutes in in vivo studies with small animals. Consequently, the Phase 1 results seem enough to make allometric scaling to assessment dose in PRRT. (author)

  8. Patterns of scintigraphic uptake in the fetlock joint of Thoroughbred racehorses and the effect of increased radiopharmaceutical uptake in the distal metacarpal/tarsal condyle on performance.

    Science.gov (United States)

    Trope, G D; Anderson, G A; Whitton, R C

    2011-09-01

    The effect of palmar osteochondral disease lesions on performance of Thoroughbred (TB) racehorses is unclear. There is a need to describe patterns of radiopharmaceutical uptake (IRU) in fetlock joints of TB racehorses and to evaluate post scintigraphy performance. IRU in the metacarpal (MC) and metatarsal (MT) condyles is more common than IRU in the parasagittal grooves and is associated with poorer post diagnosis performance than controls. Location of IRU within the fetlock region was identified and graded subjectively in TB racehorses. Performance variables were determined from race records for horses with moderate/marked MC/MT condylar IRU (cases), other horses undergoing scintigraphy (scintigraphy controls) and age/sex matched controls from the last race in which a case participated (controls). Statistical analyses included quantile regression, Fisher's exact test, Kaplan-Meier survival curves, log-rank test and Cox regression. Metacarpal/MT condylar IRU was identified in 103/220 horses with only 3/220 having parasagittal IRU. Moderate/marked IRU was identified in the MC and MT condylar regions in 62 and 39 horses, respectively, with palmaromedial and plantarolateral IRU most common. Fore- and hindlimb cases had fewer starts, reduced earnings (Pfetlock joint. Racehorses with moderate/marked condylar IRU have a shortened racing career, are less successful than age/sex matched controls and are older than other racehorses presented for scintigraphy. Overload of the MC/MT condyles is a common and significant problem in TB racehorses that is readily identified with scintigraphy. Scintigraphy of horses that are lame or performing poorly is less useful for screening for potential condylar fractures. © 2011 EVJ Ltd.

  9. Lymphoscintigraphy to evaluate the effects of upper body dynamic exercise and handgrip exercise on radiopharmaceutical clearance from hands of healthy females.

    Science.gov (United States)

    Lane, Kirstin; Worsley, Dan; McKenzie, Don

    2005-01-01

    Currently, there is not a standardized protocol to evaluate lymphatic function in women. Therefore, the purpose of this study was to evaluate the effects of arm crank ergometry (AC) and handgrip contractions (HG) on radiopharmaceutical clearance from the hands of six healthy females. On separate days, subjects performed AC (six repeated bouts of arm cranking for 5 min at 0.6 Watts.kilogram(-1) (W.kg(-1)) followed by 5 min rest) or HG (twelve repeated bouts of 75 contractions in 2.5 min at 50% MVC followed by 2.5 min of rest). HG was done with the right hand only while the left hand served as a control (CON). Prior to the start of exercise, (99m)Tc-antimony colloid was injected into the first and fourth finger-web of each hand, and 1 min spot views were taken immediately after the injection and then again every 10 min over 60 min. Clearance from the injection sites was linear and expressed as a slope (% administered activity.min(-1)). Significantly faster clearance was observed with AC (rt = -0.27 +/- 0.03 %.min(-1); left = -0.29 +/- 0.06 %.min(-1)) compared to both HG (-0.18 +/- 0.03 %.min(-1)) and CON (-0.14 +/- 0.05 %.min(-1); p = 0.000). The results indicate that AC may be more effective in promoting lymphatic clearance from the hand and may be a useful protocol to challenge the lymphatic system in breast cancer survivors.

  10. Technetium-99m-Labeled Sulfadiazine: a Targeting Radiopharmaceutical for Scintigraphic Imaging of Infectious Foci Due To Escherichia coli in Mouse and Rabbit Models.

    Science.gov (United States)

    Ahmed, Muhammad Tauqeer; Naqvi, Syed Ali Raza; Rasheed, Rashid; Zahoor, Ameer Fawad; Usman, Muhammad; Hussain, Zaib

    2017-03-11

    Bacterial infection is one of the vital reasons of morbidity and mortality, especially in developing countries. It appears silently without bothering the geological borders and imposes a grave threat to humanity. Nuclear medicine technique has an important role in helping early diagnosis of deep-seated infections. The aim of this study was to develop a new radiopharmaceutical (99m)Tc-labeling sulfadiazine as an infection imaging agent. Radiolabeling of sulfadiazine with technetium-99m ((99m)Tc) was carried out using stannous tartrate as a reducing agent in the presence of gentistic acid at pH = 5. The quality control tests revealed ~98% labeling efficiency. Paper chromatographic (PC) and instant thin-layer chromatographic (ITLC) techniques were used to analyze radiochemical yield. Biodistribution and infection specificity of the radiotracer were performed with Escherichia coli (E. coli) infection-induced rats. Scintigraphy and glomerular filtration rate (GFR) study was performed in E. coli-infected rabbits. Scintigraphy indicated E. coli infection targeting potential of (99m)Tc-SDZ, while biodistribution study showed minimal uptake of (99m)Tc-SDZ in non-targeted tissues. The uptake in the kidneys was found 2.56 ± 0.06, 2.09 ± 0.10, and 1.68 ± 0.09% at 30 min, 1 h, and 4 h, respectively. The infected muscle (target) to non-infected muscle (non-target) ratio (T/NT) was found 4.49 ± 0.04, 6.78 ± 0.07, and 5.59 ± 0.08 at 30 min, 1 h, and 4 h, respectively.

  11. Simplified NaCl based (68)Ga concentration and labeling procedure for rapid synthesis of (68)Ga radiopharmaceuticals in high radiochemical purity.

    Science.gov (United States)

    Mueller, Dirk; Klette, Ingo; Baum, Richard P; Gottschaldt, M; Schultz, Michael K; Breeman, Wouter A P

    2012-08-15

    A simple sodium chloride (NaCl) based (68)Ga eluate concentration and labeling method that enables rapid, high-efficiency labeling of DOTA conjugated peptides in high radiochemical purity is described. The method utilizes relatively few reagents and comprises minimal procedural steps. It is particularly well-suited for routine automated synthesis of clinical radiopharmaceuticals. For the (68)Ga generator eluate concentration step, commercially available cation-exchange cartridges and (68)Ga generators were used. The (68)Ga generator eluate was collected by use of a strong cation exchange cartridge. 98% of the total activity of (68)Ga was then eluted from the cation exchange cartridge with 0.5 mL of 5 M NaCl solution containing a small amount of 5.5 M HCl. After buffering with ammonium acetate, the eluate was used directly for radiolabeling of DOTATOC and DOTATATE. The (68)Ga-labeled peptides were obtained in higher radiochemical purity compared to other commonly used procedures, with radiochemical yields greater than 80%. The presence of (68)Ge could not be detected in the final product. The new method obviates the need for organic solvents, which eliminates the required quality control of the final product by gas chromatography, thereby reducing postsynthesis analytical effort significantly. The (68)Ga-labeled products were used directly, with no subsequent purification steps, such as solid-phase extraction. The NaCl method was further evaluated using an automated fluid handling system and it routinely facilitates radiochemical yields in excess of 65% in less than 15 min, with radiochemical purity consistently greater than 99% for the preparation of (68)Ga-DOTATOC.

  12. The effect of imaging time, radiopharmaceutical, full fat milk and water on interfering extra-cardiac activity in myocardial perfusion single photon emission computed tomography.

    Science.gov (United States)

    Peace, Richard A; Lloyd, Jim J

    2005-01-01

    Extra-cardiac activity can interfere with observer interpretation of myocardial perfusion single photon emission computed tomography (SPECT) images. Fatty meals and drinks to reduce interference have been tested; however, a simple study of delayed imaging with (99m)Tc-tetrofosmin and (99m)Tc-sestamibi has not been specifically addressed. The aim was to quantify the effects of imaging time, radiopharmaceutical and oral administration of full fat milk and water on interfering activity. Myocardial perfusion SPECT images were acquired using either tetrofosmin or sestamibi. Patients were imaged at 0.5, 1 or 2 h post-injection (tetrofosmin, 59; sestamibi, 72). Additional groups of patients were imaged either with or without milk (tetrofosmin, 54; sestamibi, 45) and with milk and water (sestamibi, 30). A myocardial region was drawn on the anterior projection and a thin adjacent extra-cardiac region was generated automatically. The count density ratio was calculated and validated with a trial of five observers. A decreasing ratio correlated significantly with observer rank of increasing interference with SPECT image interpretation (r=0.95, P=0.001). The ratio improved significantly as the imaging time increased for both tetrofosmin and sestamibi groups (Pmilk or milk plus water showed no significant improvement against control groups (P > or = 0.2). There was no significant difference between tetrofosmin and sestamibi at any time point (P > or = 0.4). Image interpretation may be improved by delayed imaging for tetrofosmin and sestamibi. However, in contrast with common practice, the administration of milk or water appears to be of no clinical value compared with delayed imaging, and there is no significant difference between interfering activity from tetrofosmin and sestamibi.

  13. Binding of ReO4(-) with an engineered MoO4(2-)-binding protein: towards a new approach in radiopharmaceutical applications.

    Science.gov (United States)

    Aryal, Baikuntha P; Brugarolas, Pedro; He, Chuan

    2012-01-01

    Radiolabeled biomolecules are routinely used for clinical diagnostics. (99m)Tc is the most commonly used radioactive tracer in radiopharmaceuticals. (188)Re and (186)Re are also commonly used as radioactive tracers in medicine. However, currently available methods for radiolabeling are lengthy and involve several steps in bioconjugation processes. In this work we present a strategy to engineer proteins that may selectively recognize the perrhenate (ReO(4)(-)) ion as a new way to label proteins. We found that a molybdate (MoO(4)(2-))-binding protein (ModA) from Escherichia coli can bind perrhenate with high affinity. Using fluorescence and isothermal titration calorimetry measurements, we determined the dissociation constant of ModA for ReO(4)(-) to be 541 nM and we solved a crystal structure of ModA with a bound ReO(4)(-). On the basis of the structure we created a mutant protein containing a disulfide linkage, which exhibited increased affinity for perrhenate (K(d) = 104 nM). High-resolution crystal structures of ModA (1.7 Å) and A11C/R153C mutant (2.0 Å) were solved with bound perrhenate. Both structures show that a perrhenate ion occupies the molybdate binding site using the same amino acid residues that are involved in molybdate binding. The overall structure of the perrhenate-bound ModA is unchanged compared with that of the molybdate-bound form. In the mutant protein, the bound perrhenate is further stabilized by the engineered disulfide bond. © SBIC 2011

  14. Preparation and stability of the {sup 99m} Tc-HNE{sub 2} radiopharmaceutical; Preparacion y estabilidad del radiofarmaco {sup 99m} TC-HNE{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Estrada T, J

    2002-07-01

    A radiopharmaceutical is all substance containing a radioactive atom inside of its structure and what because of its pharmaceutical form, quantity and quality of radiation can be administered in the human beings with diagnostic or therapeutic aims. With the purpose to developing effective radiopharmaceuticals it is necessary to pick carefully the appropriate radionuclide in combination with the In vivo localization and the pharmacon kinetic properties of the carrier molecule. The peptides are designed by the nature to stimulate, regulate or inhibit numerous life functions, they act mainly as information transmitters and activity coordinators of several tissues in the body; it has been found that such substances are present in cells and in the body fluids in quantities extremely small, therefore the peptides have been considered as ideal agents for therapeutic applications. Elastase of human neutrophylls is a 29 kDa protease which is produced in high levels inside the neutrophyll and it is released as response for an inflammatory stimulus in infection/inflammation places. Once it liberated is quickly inhibited by the anti elastase {alpha} tripsine (HNE-2) peptide. Therefore, the neutrophylls elastase is considered as a target to obtain In vivo images of inflammatory/infectious processes by the intravenous application of {sup 99m} Tc-HNE-2. The objective of this work was to develop a labelling method with {sup 99m} Tc for the inhibitor peptide of the human neutrophyll elastase (HNE-2). Likewise, for evaluating its In vivo and In vitro stabilities. The methodology which was followed as first step to conjugate the (HNE-2) peptide with the bi chelating agents HYNIC and DTPA capable to chelate the {sup 99m} Tc metal. Therefore the attachment reactions to the peptide were realized starting from the NHS and HYNIC and the DTPA anhydride in buffer of 0.1 M, pH= 9.0/DMF (10:1) bicarbonates with a molar relation peptide/bi chelating agent 1:5. For the purification of the

  15. Use of LC-MS for the quality control of radiopharmaceuticals: example of [(18)F]ML10.

    Science.gov (United States)

    Reiley, Richard R; Huiban, Mickael; Bennacef, Idriss; Passchier, Jan

    2013-05-30

    [(18)F]ML10 is a promising novel low molecular weight positron emission tomography probe for apoptosis. As part of the quality control to support clinical studies for cancer therapy monitoring in the GSK Clinical Imaging Centre, a simple and sensitive liquid chromatography mass spectrometry method has been developed and validated for the quantification of total ML10 and impurity content in the final product. Chromatographic separation of ML10 and its radiolabelling precursor and impurities was achieved. Mass curves were constructed from a concentration range of ML10 and known impurities and were linear. Quantification was achieved by comparison of the area under the curve for ML10 content (m/z = 205) and the mass curve. The method was validated over a concentration range of 0.1-1 µg/ml. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Synthesis and evaluation of Lys{sup 1}(α, γ-Folate)Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin(1-14) as a potential theranostic radiopharmaceutical for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aranda L, L.; Ferro F, G.; Azorin V, E.; Ramirez, F. M.; Ocampo G, B.; Santos C, C.; Jimenez M, N. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Issac O, K. [Universidad Autonoma del Estado de Mexico, Facultad de Medicina, 50180 Toluca, Estado de Mexico (Mexico)

    2015-10-15

    Full text: Lutetium-177 labeled hetero bivalent molecules that interact with different targets on tumor cells have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this work was to synthesize Lys{sup 1} (α,γ-Folate)-Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin (1-14) ({sup 177}LuFolate-Bn), as well as to assess its in vitro and in vivo potential for molecular imaging and targeted radiotherapy of breast tumors expressing folate receptors (Fr) and gastrin releasing peptide receptors (GRPR). Lys{sup 1} Lys{sup 3} (DOTA)-Bombesin (1-14) was conjugated to the terminal carboxylic group of the folic acid and the product purified by size-exclusion HPLC. Chemical characterization was carried out by UV-vis, Ft-IR spectroscopies and MALDI-TOF mass spectrometry. {sup 177}Lu labeling was performed by reaction of {sup 177}LuCl{sub 3} with the Lys{sup 1} (α,γ-Folate)-Lys{sup 3} (DOTA)-Bombesin (Folate-Bn) conjugate. In vitro binding studies were carried out in T47D breast cancer cells (positive to Fr and GRPR). Biokinetic studies and micro-SPECT/CT images were obtained using athymic mice with T47D induced tumors. Spectroscopic studies and HPLC analyses indicated that the conjugate was obtained with high chemical and radiochemical purity (98 ± 1.3%). T47D-tumors were clearly visible with high contrast at 2 h after radiopharmaceutical administration. The {sup 177}Lu-absorbed dose delivered to tumors was 23.9 ± 2.1 Gy (74 MBq, intravenously administered) {sup 177}Lu-Folate-Bn demonstrated properties suitable as a theranostic radiopharmaceutical for breast tumors expressing Fr s and GRPR s. (Author)

  17. Therapeutical radiopharmaceuticals based In vivo generator system [{sup 166} Dy] Dy/{sup 166} Ho; Radiofarmacos terapeuticos basados en un sistema de generador In vivo [{sup 166}Dy] Dy/{sup 166}Ho

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Garcia S, L.; Monroy G, F.; Tendilla, J.I. [Gerencia de Aplicaciones Nucleares en la Salud, ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico); Pedraza L, M.; Murphy, C.A. de [Departamento de Medicina Nuclear, Instituto Nacional de Pediatria, Mexico D.F. (Mexico)

    2002-07-01

    At the idea to administer to a patient a molecule containing in it structure a father radionuclide, with a half life enough large which allows to the radiolabelled molecule to take up position specifically in a white tissue and decaying In vivo to the daughter radionuclide with properties potentially therapeutic, it is known as In vivo generator system. In this work the preparation and the preliminary dosimetric valuations of radiopharmaceuticals based In vivo generator system {sup 166} Dy Dy/{sup 166} Ho for applications in radioimmunotherapy, in the treatment of the rheumatoid arthritis and in the bone marrow ablation (m.o.) for candidates patients to bone marrow transplant are presented. (Author)

  18. Study of the production of the radiopharmaceutical {sup 18}F-FLT in automated system: contribution for process validation; Estudo da producao do radiofarmaco FLT-{sup 18}F em sistema automatizado: contribuicao para a validacao do processo

    Energy Technology Data Exchange (ETDEWEB)

    Zanette, Camila

    2013-07-01

    Radiopharmaceutical {sup 18}F-FLT is a thymidine nucleoside analogue and a promising tumor proliferation marker for PET images. The synthesis of this radiopharmaceutical is not simple, and often has low yields. This radiopharmaceutical has already been studied for some years; however, there is no production, nor are there clinical studies in Brazil. The study of the production process and its compliance with the guidelines of Good Manufacturing Practices (ANVISA) are of extreme importance. This study aimed to investigate the synthesis of this radiopharmaceutical, evaluate methods of quality control that will be used in future production routines, perform cytotoxicity studies, biodistribution studies and PET imaging in animals, thereby contributing to the development and elaboration of the process validation protocol and to the establishment of analytical methods to be used during production routines. Initially, we studied the synthesis and production of {sup 18}F-FLT, with the evaluation of three different temperatures of radiolabeling to check the behavior of the radiochemical yield and stability of the nal product. Studies of analytical methodology comprised the analysis of radionuclide identification, determination of chromatographic profiles, radiochemical purity, residual solvents, and pH. In vitro studies of internalization and cytotoxicity were also carried out. In in vivo studies, we evaluated the pharmacokinetics, biodistribution in healthy animals and in animals with tumor models, in addition to PET/CT images in animals with melanomas. The final product had high radiochemical purity and was stable for up to 10 hours after the synthesis, but got a relatively low radiochemical yield, as described in the literature. The tested analytical methods proved suitable for use in the quality control of {sup 18}F-FLT. In in vitro studies, {sup 18}F-FLT showed a significant percentage of binding to tumor cells, and the nonradiolabeled molecule was not considered toxic

  19. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor; Desenvolvimento de nanorradiofarmaco a base de Bevacizumabe marcado com tecnecio-99m para diagnostico precoce do tumor estromal gastrointestinal

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Thais Ligiero

    2015-06-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  20. Impurity radionuclide analysis for the radiopharmaceutical Na[{sup 123}I] using gamma spectrometry; Analise de impurezas radionuclidicas para o radiofarmaco Na[{sup 123}I] utilizando a espectrometria gama

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Miriam Taina Ferreira de; Silva, Ronaldo Lins da; Poledna, Roberto; Delgado, Jose Ubiratan; Andrade, Erica de Araujo Lima de; Oliveira, Antonio Eduardo de; Laranjeiras, Adilson Silva, E-mail: miriam@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Braghirolli, Ana Maria Silveira [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    During the process of manufacturing a radiopharmaceutical radionuclide impurities nature can be generated. With the need to meet the standards of ANVISA recommends that applications of doses as low as feasible in patients, the concern comes with a 'boost' that can come from these radionuclidic impurities generated in the production process and or manipulation. For Na[¹²³I] provided by IEN is important to quantify its major impurity, ¹²¹Te as well as gaining a better understanding of the parameters related to the decay scheme, since the data in the literature show discrepancies. (author)

  1. Pharmacokinetic properties of new antitumor radiopharmaceutical on the basis of diamond nanoporous composites labeled with rhenium-188

    Science.gov (United States)

    Petriev, V. M.; Tishchenko, V. K.; Kuril'chik, A. A.; Skvortsov, V. G.

    2017-01-01

    Today the development of address therapeutic radionuclide delivery systems directly to tumor tissue is of current interest. It can be achieved by the design of drug containers of specific sizes and shapes from carbon-based composite materials. It will be allowed to enhance the efficacy of anticancer therapy and avoid serious side effects. In this work we studied the pharmacokinetic properties of nanodiamond nanoporous composite labeled with rhenium-188 in rats with hepatocholangioma PC-1 after intratumoral injection. It was established that substantial part of injected radioactivity remained in tumor tissue. Within three hours after 188Re-nanoporous composites injection activity in tumor constituted 79.1-91.3% of injected dose (ID). Then activity level declined to 45.9% ID at 120 hours. No more than 1.34% ID entered the bloodstream. In soft organs and tissues, except thyroid gland, the content of compound didn’t exceed 0.3% ID/g. The highest activity in thyroid gland was 6.95% ID/g. In conclusion, received results suggest 188Re-nanoporous composites can be promising radionuclide delivery systems for cancer treatment.

  2. Evaluation of occupational radiation dose in nuclear medicine: radiopharmaceutical administration to scintiscanning exams of myocardial perfusion; Avaliacao da dose de radiacao ocupacional em medicina nuclear: administracao de radiofarmacos em exames de cintilografria de perfusao miocardica

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Cassio V., E-mail: cassiok@yahoo.com [Medicina Nuclear do Triangulo (MNT), Uberlandia, MG (Brazil); Michelin, Charlie A.; Jakubiak, Rosangela R., E-mail: charlie@utfpr.edu.br, E-mail: requi@utfpr.edu.br [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil); Lemes, Alyne O.; Silva, Juliana L.M., E-mail: alyne275@gmail.com, E-mail: jujumontesdocinho@gmail.com [Faculdade do Trabalho (FATRA), Uberlandia, MG (Brazil)

    2013-11-01

    In nuclear medicine, workers directly involved in exams are constantly exposed to ionizing radiation. The procedure for administration of the radiopharmaceutical to the patient is one of the most critical times of exposure. In tests of myocardial perfusion scintigraphy (MPS) administration of radiopharmaceutical repeats the steps of rest and cardiac stress. In this study, we used a Geiger -Mueller detector for measuring occupational radiation doses for during the administration of technetium- {sup 99m}- sestamibi in MPS tests. In the evaluation, discriminated the stages of examination and related professional experience time to doses measures at home. It were followed 110 procedures at home (55 conducted by professionals with over 5 years experience and 55 conducted by professionals with less than 1 year of experience) and 55 effort procedures. The results showed that the rest of the procedure time and dose are related to the experience of the worker. More experienced workers were faster (mean: 43 {+-} 16 vs 67 {+-} 25 seconds / procedure), and therefore received lower doses (mean 0.57 {+-} 0.16 versus 0.80 {+-} 0.24 {mu}Sv / procedure), both with statistical significance (p <0.001). In step effort, there were procedures lasting longer (mean: 19 {+-} 2 minutes / procedure), which resulted in higher doses (mean 3.0 {+-} 0.6 {mu}Sv / procedure)

  3. An original approach in the diagnosis of early breast cancer: use of the same radiopharmaceutical for both non-palpable lesions and sentinel node localisation

    Energy Technology Data Exchange (ETDEWEB)

    Feggi, L.; Prandini, N. [Dept. of Nuclear Medicine, S. Anna Hospital, Ferrara (Italy); Basaglia, E.; Soliani, G.; Ascanelli, S.; Bergossi, L.; Carcoforo, P. [Dept. of General Surgery, University of Ferrara (Italy); Corcione, S. [Dept. of Radiology, S. Anna Hospital, Ferrara (Italy); Querzoli, P. [Dept. of Pathology, Univ. of Ferrara (Italy)

    2001-11-01

    We propose the use of a single nanocolloid tracer which is labelled with technetium-99m for simultaneous performance of ROLL and sentinel node indentification. The aim of this study was to evaluate the feasibility of this approach, which should be easier and more practical than the dual-tracer injection method. We have employed this new technique in 73 patients with non-palpable, cytologically diagnosed breast cancer and non-palpable axillary lymph nodes. In all patients the radiocolloid, in a total volume of 0.3-0.4 cc, was injected under sonographic or stereotactic guidance. Half of the dose was injected intratumourally and half superficially, but very close to the tumour. Because of the slow lymphatic flow in the breast, Nanocoll must be injected some time before surgery in order to enable adequate migration to the axilla. We injected colloid in the afternoon before surgery (16-23 h before the start of the operation, with an average interval of 18 h). An average dose of 130 MBq (range 110-150) was injected in order to have about 10 MBq of radioactivity when surgery commenced. Lymphoscintigraphy was performed after 15-19 h, with an average interval of 17 h. The procedure was always successful in permitting the localisation of occult breast lesions. Lesions were always localised at the first attempt, and were always contained within the surgical margins. Histological examination revealed all 73 resected lesions to be malignant: there were 64 cases of infiltrating carcinoma and nine of intraductal carcinoma. All breast lesions were therefore confirmed to be early breast cancer. We achieved sentinel node localisation in 71 out of 73, either at scintigraphy or with the intraoperative probe; in two patients, radiopharmaceutical migration was absent. Lymphoscintigraphy showed only axillary drainage in 52 cases, only internal mammary chain (IMC) drainage in nine cases, and combined axillary and IMC drainage in eight cases. In two cases, lymphoscintigraphy suggested the

  4. A new radiopharmaceutical compound (131I-PR81) for radioimmunotherapy of breast cancer: labeling of antibody and its quality control.

    Science.gov (United States)

    Mohammadnejad, J; Rasaee, M J; Babaei, M H; Paknejad, M; Zahir, M H; Salouti, M; Rajabi, A Bitarafan; Mazidi, M

    2010-01-01

    PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast and other tumors. The objective of this study was to evaluate the application of this antibody against MUC1 as a radioimmunotherapeutical agent. Monoclonal antibody (PR81) against MUC1 was prepared, characterized, purified, and labeled with 131I. The immunoreactivity of radiolabeled mAb PR81with MUC1 (the native protein), BSA-P20 (a 20 amino acid corresponding the tandem repeat of MUC1) and MCF7 cell line were performed by RIA. In vitro stability of radiolabeled mAb in human serum was determined by thin layer chromatography (TLC). Cell toxicity and in vitro internalization studies were performed with the MCF7 cell line, and the tissue biodistribution of the radioiodinated PR81 was evaluated in normal BALB/c mice at 4, 24 and 48 hrs. The tumor imaging was performed in BALB/c mice with breast xenograft tumors at 24 and 72 hr after the complex injection. The labeling efficiency was found to be 59.9% ± 7.9%. MAb-131I conjugates showed high immunoreactivity towards MUC1 protein, BSA-P20 and MCF7 cell line. In vitro stability of the labeled product in human serum was found to be more than %50 over 24 hr. Cell toxicity and in vitro internalization studies showed that the mAb-131I conjugate inhibited 80% growth of the MCF7 cultured cell lines in vitro in a high concentration and up to %60 of the conjugate internalized after 24 h. Biodistribution studies were performed in normal BALB/c mice at 4, 24 and 48 hrs post-injection and no important accumulation was observed in vital organs. The tumors were visualized with high sensitivity after 24 and 72 hr in radioimmunoscintographical studies. These results show that the new radiopharmaceutical may be considered as a promising candidate for therapy of breast cancer.

  5. (segunda parte

    Directory of Open Access Journals (Sweden)

    José María Oliva-Martínez

    2004-01-01

    Full Text Available Este trabajo es la continuación de otro anterior (Oliva, 2004, ambos dedicados al estudio de la importancia del pensamiento analógico en la construcción histórica de la noción de fuerza gravitatoria y del modelo de Sistema Solar. En aquella ocasión analizamos dicho papel durante el período comprendido desde las antiguas civilizaciones hasta llegar a la revolución copernicana con científicos como Copérnico, Gilbert, Kepler o el propio Galileo. En esta segunda parte, se continúa con algunos de los razonamientos analógicos proporcionados desde la vertiente mecanicista, capitaneada por Descartes y desde la tradición subsiguiente que se desarrolló en línea con la utilización del método de la analogía como criterio argumentativo (Huyghens, Hooke, Bernoulli, etc.. Dedicamos asimismo un capítulo aparte a la figura de Newton, quien continúa con dicha tradición en su intento de explicar la naturaleza de la gravitación. Finalmente se procede, a modo de síntesis, a realizar una clasificación de distintos tipos de razonamientos analógicos aportados en el desarrollo histórico en torno a estos temas, estudiando el papel científico y divulgativo de cada uno

  6. Evaluation of the quality of the radiopharmaceutical 99mTc-MIBI and its influence on image quality in myocardial perfusion scintigraphy; Avaliacao da qualidade do radiofarmaco {sup 99m}Tc-MIBI e sua influencia na qualidade da imagem em cintilografia de perfusao do miocardio

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Poliane Angelo de Lucena

    2013-07-01

    This study evaluated the quality of the {sup 99m}Tc-MIBI radiopharmaceutical from different manufacturers, used in three nuclear medicine services (NMS) in Recife-PE, through labeling procedure of each service. It was observed their biodistribution by quantifying the activity present in the organs of interest (heart / liver), the influence and interference in image quality and in myocardial scintigraphy diagnosis exam. In these NMS (A, B and C) were done quality controls in the eluates of {sup 99}Mo/{sup 99m}Tc generators (radionuclidic, chemical and radiochemical purity and pH) and of the {sup 99m}Tc-MIBI radiopharmaceutical (radiochemical purity and pH) used in myocardial scintigraphy exam. In the case of radiochemical purity (RCP), was used the thin layer chromatography technique; after the chromatographic ran on, the plates were analyzed both in the dose calibrator, and in scintillation camera of each NMS. The radiopharmaceutical biodistribution was evaluated through the activities present in the heart and liver images in 60 patients, using the technique of combined images counting. Five nuclear physicians analyzed 24 images through myocardial perfusion visual interpretation during stress, it was verified the agreement degree among them. The results of the quality control showed that all eluate samples were in agreement with the manufacturers in relation to radionuclidic purity and pH. In relation to chemical purity, 10% of the services samples B and C showed Al{sup +3} values above 10 ppm. In the RCP, it was observed that using the scintillation camera, only 22% of the samples would be discarded, while with dose calibrator would be 78%, indicating that the scintillation camera is more sensitive in chromatographic pale analysis. For the labeled radiopharmaceutical, the services B and C presented respectively one and three samples with RCP percentage below 90%. However, C service presented the lowest medium to liver/heart proportions, showing that this factor

  7. Radiopharmaceutical and Gene Therapy Program

    Energy Technology Data Exchange (ETDEWEB)

    Buchsbaum, Donald J.

    2006-02-09

    The objective of our research program was to determine whether novel receptors can be induced in solid cancers as a target for therapy with radiolabeled unmodified peptides that bind to the receptors. The hypothesis was that induction of a high number of receptors on the surface of these cancer cells would result in an increased uptake of the radiolabeled monomeric peptides as compared to published results with radiolabeled antibodies or peptides to naturally expressed antigens or receptors, and therefore a better therapeutic outcome. The following is a summary of published results.

  8. Radiopharmaceuticals for SPECT cancer detection

    Energy Technology Data Exchange (ETDEWEB)

    Chernov, V. I., E-mail: chernov@oncology.tomsk.ru; Medvedeva, A. A., E-mail: tickayaAA@oncology.tomsk.ru; Zelchan, R. V., E-mail: r.zelchan@yandex.ru; Sinilkin, I. G., E-mail: sinilkinig@oncology.tomsk.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation); Stasyuk, E. S.; Larionova, L. A. [Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation); Slonimskaya, E. M.; Choynzonov, E. L. [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation)

    2016-08-02

    The purpose of the study was to assess the efficacy of single photon emission computed tomography (SPECT) with {sup 199}Tl and {sup 99}mTc-MIBI in the detection of breast, laryngeal and hypopharyngeal cancers. A total of 220 patients were included into the study: 120 patients with breast lesions (100 patients with breast cancer and 20 patients with benign breast tumors) and 100 patients with laryngeal/hypopharyngeal diseases (80 patients with laryngeal/hypopharyngeal cancer and 20 patients with benign laryngeal/hypopharyngeal lesions). No abnormal {sup 199}Tl uptake was seen in all patients with benign breast and laryngeal lesions, indicating a 100% specificity of {sup 199}Tl SPECT. In the breast cancer patients, the increased {sup 199}Tl uptake in the breast was visualized in 94.8% patients, {sup 99m}Tc-MIBI—in 93.4% patients. The increased {sup 199}Tl uptake in axillary lymph nodes was detected in 60% patients, and {sup 99m}Tc-MIBI—in 93.1% patients. In patients with laryngeal/hypopharyngeal cancer, the sensitivity of SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI was 95%. The {sup 199}Tl SPECT sensitivity in identification of regional lymph node metastases in the patients with laryngeal/hypopharyngeal cancer was 75% and the {sup 99m}Tc-MIBI SPECT sensitivity was 17%. The data obtained showed that SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI can be used as one of the additional imaging methods in detection of tumors.

  9. DEVELOPMENT OF RADIOPHARMACEUTICAL FOR RADIOSINOVECTOMY

    OpenAIRE

    Couto, Renata M.

    2009-01-01

    Radiofármacos marcados com diferentes radionuclídeos são utilizados em aplicações diagnósticas e terapêuticas em Medicina Nuclear. Nos últimos anos houve um aumento no interesse pela terapia radionuclídica, com a introdução de novos radiofármacos aplicados para destruir especificamente determinada célula ou impedir sua proliferação indesejável. Uma modalidade terapêutica que emprega radiofármacos é a radiosinovectomia (RSV), na qual o radiofármaco é administrado na cavidade articular, sendo u...

  10. Radiopharmaceuticals for SPECT cancer detection

    Science.gov (United States)

    Chernov, V. I.; Medvedeva, A. A.; Zelchan, R. V.; Sinilkin, I. G.; Stasyuk, E. S.; Larionova, L. A.; Slonimskaya, E. M.; Choynzonov, E. L.

    2016-08-01

    The purpose of the study was to assess the efficacy of single photon emission computed tomography (SPECT) with 199Tl and 99mTc-MIBI in the detection of breast, laryngeal and hypopharyngeal cancers. A total of 220 patients were included into the study: 120 patients with breast lesions (100 patients with breast cancer and 20 patients with benign breast tumors) and 100 patients with laryngeal/hypopharyngeal diseases (80 patients with laryngeal/hypopharyngeal cancer and 20 patients with benign laryngeal/hypopharyngeal lesions). No abnormal 199Tl uptake was seen in all patients with benign breast and laryngeal lesions, indicating a 100% specificity of 199Tl SPECT. In the breast cancer patients, the increased 199Tl uptake in the breast was visualized in 94.8% patients, 99mTc-MIBI—in 93.4% patients. The increased 199Tl uptake in axillary lymph nodes was detected in 60% patients, and 99mTc-MIBI—in 93.1% patients. In patients with laryngeal/hypopharyngeal cancer, the sensitivity of SPECT with 199Tl and 99mTc-MIBI was 95%. The 199Tl SPECT sensitivity in identification of regional lymph node metastases in the patients with laryngeal/hypopharyngeal cancer was 75% and the 99mTc-MIBI SPECT sensitivity was 17%. The data obtained showed that SPECT with 199Tl and 99mTc-MIBI can be used as one of the additional imaging methods in detection of tumors.

  11. Recent applications of nuclear medicine in diagnostics: II part

    Directory of Open Access Journals (Sweden)

    Giorgio Treglia

    2013-04-01

    Full Text Available Introduction: Positron-emission tomography (PET and single photon emission computed tomography (SPECT are effective diagnostic imaging tools in several clinical settings. The aim of this article (the second of a 2-part series is to examine some of the more recent applications of nuclear medicine imaging techniques, particularly in the fields of neurology, cardiology, and infection/inflammation. Discussion: A review of the literature reveals that in the field of neurology nuclear medicine techniques are most widely used to investigate cognitive deficits and dementia (particularly those associated with Alzheimer disease, epilepsy, and movement disorders. In cardiology, SPECT and PET also play important roles in the work-up of patients with coronary artery disease, providing accurate information on the state of the myocardium (perfusion, metabolism, and innervation. White blood cell scintigraphy and FDG-PET are widely used to investigate many infectious/inflammatory processes. In each of these areas, the review discusses the use of recently developed radiopharmaceuticals, the growth of tomographic nuclear medicine techniques, and the ways in which these advances are improving molecular imaging of biologic processes at the cellular level.

  12. Optimization of the production process of a lyophilized formulation for radiopharmaceutical obtaining {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]{sub 2}; Optimizacion del proceso de fabricacion de una formulacion liofilizada para la obtencion del radiofarmaco {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez R, S.

    2013-07-01

    In this work was optimized the production process of a lyophilized pharmaceutical formulation for the preparation of radiopharmaceutical {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]{sub 2}, the union specifies to the integrin s α{sub v}β{sub 3} was demonstrated to be used in the nuclear medicine cabinets in the obtaining of scan images for the opportune detection of breast cancer. The good lyophilized pharmaceutical formulation for the preparation of radiopharmaceutical {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]{sub 2} was established like: HYNIC-E-[c(RGDfK)]{sub 2} - 25 μg; Stannous chloride (SnCl{sub 2}) 20 μg; Ethylenediamine diacetic acid (EDDA) 10 mg; N-tris(hydroxymethyl)methyl glycin (Tricine) 20 mg; Mannitol 50 mg. The results of radiochemical purity of the sterile formulation and free of bacterial endotoxins for the three validation lots prepared under protocols of good manufacturing practices were 97.62 ± 1.48%, 96.54 ± 1.89%, and 97.66 ± 0.57%, for what the production procedure complies the predefined specifications. The radiopharmaceutical {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]2 prepared from the lyophilized pharmaceutical formulation showed to be stable during a period 24 hours, for what can be used in the centers of molecular nuclear medicine. Images in vivo were obtained of the integrin s over-expression α{sub v}β{sub 3} from the radiopharmaceutical {sup 99m}Tc-EDDA/HYNIC-E-[c(RGDfK)]2 obtained of the lyophilized and optimized pharmaceutical formulation. The lyophilized pharmaceutical formulation (HYNIC-RGD-Sn) showed stability during 12 months, due to this factor, is requested before the COFEPRIS the radiopharmaceutical expiration for this same period (accession number 123300401A0155). (Author)

  13. Study of the radioactive impurities gamma emitters present in the radiopharmaceutical solutions produced at IPEN/CNEN-SP; Estudo das impurezas radioativas gama emissoras presentes nos radiofarmacos produzidos no IPEN-CNEN/SP

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Jamille da Silveira

    2017-11-01

    This work aims to investigate the concentration of radioactive impurities gamma emitters in the radiopharmaceutical solutions produced at Nuclear and Energy Research Institute -IPEN in Sao Paulo, So that this radiopharmaceutical may be used properly, its quality should be evaluated in accordance with the procedures established by quality control agencies, such as General Requirements for the Competence of Testing and Calibration Laboratories' ISO/IEC 17025:2005 and the 'Good Laboratory Practice (GLP), controlled by ANVISA (National Agency Health Surveillance), in Brazil, requiring a confirmation of the values of impurities related at the certificates supplied by the manufacturers. To determine the activity, a high resolution gamma spectrometer were used in two source-detector distances. One was 18 cm and the other 1.7 cm. For the 18 cm distance, the high pure germanium spectrometer was calibrated in the energy range between 81 keV and 1408 keV by measuring sealed ampoules of {sup 60}Co, {sup 133}Ba, {sup 137}Cs and {sup 152}Eu, standardized at the Nuclear Metrology Laboratory (NML) of IPEN. For lower activity of the impurities, the distance source-detector of 1.7 cm was assumed. However, as at this distance, the sum coincidence effect is very high, making the measurement of the standard calibration ampoules difficult, the spectrometer efficiency curve was obtained by a Monte Carlo simulation code, developed at IPEN. In this code, all details of the detection system are modeled and the response curves for x-rays and gamma rays are calculated by the MCNPX radiation transport code. The gamma spectra were analyzed by Alpino code, which applies the method of numeric peak integration of the area under the photopeaks. For gamma emitter impurities, not visually detected, the decision threshold and the detection limits were calculated from the background count rate, under the peak area. The radiopharmaceutical solutions analyzed were {sup 67}Ga, {sup 99}Mo, {sup

  14. Evaluation of the bubble point test of a 0.22-μm membrane filter used for the sterilizing filtration of PET radiopharmaceuticals.

    Science.gov (United States)

    Hayashi, Kazutaka; Douhara, Kazumasa; Kashino, Genro

    2014-07-01

    .3 kPa and 390.3 ± 7.6 kPa, respectively. All results of the water-wetted bubble point test were beyond the filter manufacturer's minimum bubble point specification (344.8 kPa). The bubble point test technique using the bubble point test kit was practical for routine quality control tests of PET radiopharmaceuticals.

  15. Synthesis, quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the Center for Development of Nuclear Technology - CDTN

    Directory of Open Access Journals (Sweden)

    Marina Bicalho Silveira

    2010-09-01

    Full Text Available 18F-Sodium fluoride (Na18F is a radiopharmaceutical used for diagnosis in nuclear medicine by positron emission tomography (PET imaging. Bone scintigraphy is normally performed using 99mTc-MDP. However, 18F PET scans promise high quality imaging with increased resolution and improved sensitivity and specificity. In order to make available a tool for more specific studies of tumors and non-oncological diseases of bone tissue, the UPPR/CDTN team undertook the production and quality control of Na18F injectable solution with the physical-chemical, microbiological and biological characteristics recommended in the U.S. Pharmacopeia. Na18F radiochemical purity was 96.7 ± 1.3 %, with Rf= 0.026 ± 0.006. The product presented a pH of 5.3 ± 0.6, half life of 109.0 ± 0.8 minutes, endotoxin limit O Fluoreto de sódio 18F (Na18F é um radiofármaco empregado para diagnóstico através da Tomografia por Emissão de Pósitrons (PET. Cintilografias ósseas são normalmente obtidas utilizando-se 99mTc-MDP. Entretanto, o interesse pelo Na18F é crescente, principalmente devido à obtanção de imagens de elevada resolução. Com o objetivo de tornar disponível uma ferramenta mais específica para estudos de tumores e doenças não-oncológicas do tecido ósseo, o grupo da UPPR/CDTN implementou a produção e o controle de qualidade da solução injetável de Na18F com as características físico-química, microbiológica e biológica preconizadas pela farmacopéia. Sua pureza radioquímica foi de 96,7 ± 1,3 %, com Rf= 0,026 ± 0,006. O produto apresentou pH igual a 5,3 ± 0,6, tempo de meia-vida de 109,0 ± 0,8 minutos, limite de endotoxinas < 5,0 EU.mL-1 e ausência de microrganismos. O perfil de biodistribuição em camundongos foi semelhante ao disponível na literatura, com depuração igual a 0,19 mL.min-1 e volume de distribuição igual a 18,76 mL. A concentração máxima (5,0 ± 0,5 % DI.g-1 foi observada no osso 20 minutos após a injeção. O Na18

  16. Development of aptamers for use as radiopharmaceuticals in the bacterial infection identification; Desenvolvimento de aptameros especificos para aplicacao como radiofarmacos na identificacao de bacterias

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Ieda Mendes

    2013-08-01

    The difficulty in early detection of specific foci caused by bacteria in the bacterial infection has raised the need to search for new techniques for this purpose, since these foci require prolonged treatment with antibiotics and in some cases even drainage or, if applicable, removal of prostheses or grafts. Detection of bacterial infections by scintigraphy had the advantage that a whole body image could be obtained, since specific tracers were available. This study aims to obtain aptamers specific for bacteria identification for future use as radiopharmaceutical. The SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology can generate oligonucleotides (aptamers) that are able to bind with high affinity and specificity to a specific target, from small molecules to complex proteins, by using rounds of enrichment and amplification. Aptamers can be labeled with different radionucleotides such as {sup 99}mTc, {sup 18}F and {sup 32}P. In this study, aptamers anti-peptidoglycan, the main component of the bacterial outer cell wall, were obtained through SELEX. Whole cells of Staphylococcus aureus were also used to perform the SELEX to cells (cell-SELEX). The selection of aptamers was performed by two different procedures (A and B). The A process has been accomplished by 15 SELEX rounds in which the separation of the oligonucleotides bound to the peptidoglycan of unbound ones was performed by filtration. In the B process 15 SELEX rounds were performed using the centrifugation for this separation, followed by 5 rounds cell-SELEX. The SELEX started with a pool of ssDNA (single stranded DNA). For A process, initially a library of ssDNA was incubated with peptidoglycan and the amplification of oligonucleotides that were able to bind to peptidoglycan was performed by PCR (Polymerase Chain Reation). The amplified oligonucleotides were again incubated with peptidoglycan, amplified and purified. At the end of 15 selection rounds the selected oligonucleotides

  17. Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals

    Science.gov (United States)

    Kuntzsch, Matthias; Lamparter, Denis; Brüggener, Nils; Müller, Marco; Kienzle, Gabriele J.; Reischl, Gerald

    2014-01-01

    Kryptofix® 2.2.2 (Kry) or tetrabutylammonium (TBA) are commonly used as phase transfer catalysts in 18F-radiopharmaceutical productions for positron emission tomography (PET). Due to their toxicity, quality control has to be performed before administration of the tracer to assure that limit concentration of residual reagent is not reached. Here, we describe the successful development and pharmaceutical validation (for specificity, accuracy and detection limit) of a simplified color spot test on TLC plates. We were able to prove its applicability as a general, time and resources saving, easy to handle and reliable method in daily routine analyzing 18F-tracer formulations for Kry (in [18F]FDG or [18F]FECh) or TBA contaminations (in [18F]FLT) with special regard to complex matrix compositions. PMID:24830987

  18. Study of the production yields of {sup 18}F, {sup 11}C, {sup 13}N and {sup 15}O positron emitters from plasma-laser proton sources at ELI-Beamlines for labeling of PET radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Amato, Ernesto [Section of Radiological Sciences, Department of Biomedical and Dental Sciences and of Morphologic and Functional Imaging, University of Messina (Italy); Italiano, Antonio, E-mail: italianoa@unime.it [Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Messina (Italy); Margarone, Daniele [Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, 182 21 Prague (Czech Republic); Pagano, Benedetta [Nuclear Medicine Unit, University Hospital “G. Martino”, Messina (Italy); Baldari, Sergio [Section of Radiological Sciences, Department of Biomedical and Dental Sciences and of Morphologic and Functional Imaging, University of Messina (Italy); Nuclear Medicine Unit, University Hospital “G. Martino”, Messina (Italy); Korn, Georg [Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, 182 21 Prague (Czech Republic)

    2016-03-01

    The development of novel compact PET radionuclide production systems is of great interest to promote the diffusion of PET diagnostics, especially in view of the continuous development of microfluidics labeling approaches. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources such that expected at the ELI-Beamlines facility. {sup 18}F, {sup 11}C, {sup 13}N and {sup 15}O production yields were calculated through the TALYS software, by taking into account the broad proton spectra expected. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of {sup 18}F-, {sup 11}C- and {sup 13}N-labeled radiopharmaceuticals exploiting fast and efficient microfluidic labeling systems.

  19. Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Matthias Kuntzsch

    2014-05-01

    Full Text Available Kryptofix® 2.2.2 (Kry or tetrabutylammonium (TBA are commonly used as phase transfer catalysts in 18F-radiopharmaceutical productions for positron emission tomography (PET. Due to their toxicity, quality control has to be performed before administration of the tracer to assure that limit concentration of residual reagent is not reached. Here, we describe the successful development and pharmaceutical validation (for specificity, accuracy and detection limit of a simplified color spot test on TLC plates. We were able to prove its applicability as a general, time and resources saving, easy to handle and reliable method in daily routine analyzing 18F-tracer formulations for Kry (in [18F]FDG or [18F]FECh or TBA contaminations (in [18F]FLT with special regard to complex matrix compositions.

  20. Potential pitfalls in the nuclear medicine imaging: Experimental models to evaluate the effect of natural products on the radiolabeling of blood constituents, bioavailability of radiopharmaceutical and on the survival of Escherichia coli strains submitted to the treatment with stannous ion

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Scheila F. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Brito, Lavinia C. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Souza, Deise E. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Bernardo, Luciana C. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Oliveira, Joelma F. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Bernardo-Filho, Mario [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil)]. E-mail: bernardo@uerj.br

    2006-12-20

    Single photon emission computed tomography (SPECT) allows studies of physiological or pathological processes. Red blood cells labeled with technetium-99m ({sup 99m}Tc-RBC) are used as a radiopharmaceutical in several evaluations. The radiolabeling efficiency and bioavailability of radiopharmaceuticals can be altered by natural/synthetic drugs and may induce pitfalls in the analysis of the nuclear medicine imaging. The labeling with {sup 99m}Tc requires a reducing agent and stannous chloride (SnCl{sub 2}) is widely utilized. However, SnCl{sub 2} presents a citotoxic and/or genotoxic potential in Escherichia coli (E. coli) strains. The aim of this work was to evaluate the influence of aqueous extracts of Baccharis genistelloides (BG), Terminalia chebula (TC), Maytenus ilicifolia (MI), Cassia angustifolia (CA) and Equisetum arvense (EA) on (i) radiolabeling of blood constituents (ii) bioavailability of sodium pertechnetate(Na{sup 99m}TcO{sub 4}) radiopharmaceutical (iii) survival of E. coli. In vitro labeling of RBC was performed with blood (Wistar rats) incubated with each extract, SnCl{sub 2} and Na{sup 99m}TcO{sub 4}. Plasma (P) and blood cells (BC) were isolated, another aliquots precipitated and soluble (SF) and insoluble (IF) fractions isolated and counted. In the bioavailability of Na{sup 99m}TcO{sub 4}, Wistar rats were treated (7 days) with aqueous extract or with 0.9%NaCl, the radiopharmaceutical was administered, the animals sacrificed, the organs isolated, weighted and radioactivity counted. To evaluate the effect on the bacterial survival, E. coli was treated with: (a) SnCl{sub 2}; (b) 0.9% NaCl; (c) vegetal extract; or (d) SnCl{sub 2} and vegetal extract. Radiolabeling efficiency showed a significantly decrease (ANOVA/Tukey post-test, p<0.05) after treatment with BG, TC, MI and CA extracts. The bioavailability results showed that the uptake of Na{sup 99m}TcO{sub 4} was altered significantly (unpaired t-student test, p<0.05) in blood, lungs (CA

  1. In vitro and in vivo studies of an aqueous extract of Matricaria recutita (German chamomile) on the radiolabeling of blood constituents, on the morphology of red blood cells and on the biodistribution of the radiopharmaceutical sodium pertechnetate.

    Science.gov (United States)

    Garcia-Pinto, Angélica B; Santos-Filho, Sebastião D; Carvalho, Jorge J; Pereira, Mário J S; Fonseca, Adenilson S; Bernardo-Filho, Mário

    2013-10-01

    Natural products might alter the labeling of blood constituents with technetium-99m ((99m)Tc) and these results may be correlated with modifications of the shape of the red blood cells (RBC). The biodistribution of radiopharmaceuticals can be also altered. This investigation aimed to determine biological effects of an aqueous extract of chamomile (CE). To study the effect of the CE on the labeling of blood constituents with (99m)Tc, in vitro and in vivo assays were performed. The effect of the CE on the morphology of RBC was observed under light microscope. The images were acquired, processed, and the perimeter/area ratio of the RBC determined. To analyze the effect of the CE on biodistribution of the sodium pertechnetate (Na(99m)TcO4) in Wistar rats, these animals were treated or not with a CE. Na(99m)TcO4 was injected, the rats were sacrificed, the organs were removed, weighted and percentage of radioactivity/gram calculated. In the in vitro experiment, the radioactivity on blood cells compartment and on insoluble fractions of plasma was diminished. The shape and the perimeter/area ratio of the RBC were altered in in vitro assays. An increase of the percentage of radioactivity of Na(99m)TcO4 was observed in stomach after in vivo treatment. These results could be due to substances of the CE or by the products of the metabolism of this extract in the animal organism. These findings are examples of drug interaction with a radiopharmaceutical, which could lead to misdiagnosis in clinical practice with unexpected consequences.

  2. In vitro and in vivo studies of an aqueous extract of Matricaria recutita (German chamomile) on the radiolabeling of blood constituents, on the morphology of red blood cells and on the biodistribution of the radiopharmaceutical sodium pertechnetate

    Science.gov (United States)

    Garcia-Pinto, Angélica B.; Santos-Filho, Sebastião D.; Carvalho, Jorge J.; Pereira, Mário J. S.; Fonseca, Adenilson S.; Bernardo-Filho, Mário

    2013-01-01

    Background: Natural products might alter the labeling of blood constituents with technetium-99m (99mTc) and these results may be correlated with modifications of the shape of the red blood cells (RBC). The biodistribution of radiopharmaceuticals can be also altered. Objective: This investigation aimed to determine biological effects of an aqueous extract of chamomile (CE). Materials and Methods: To study the effect of the CE on the labeling of blood constituents with 99mTc, in vitro and in vivo assays were performed. The effect of the CE on the morphology of RBC was observed under light microscope. The images were acquired, processed, and the perimeter/area ratio of the RBC determined. To analyze the effect of the CE on biodistribution of the sodium pertechnetate (Na99mTcO4) in Wistar rats, these animals were treated or not with a CE. Na99mTcO4 was injected, the rats were sacrificed, the organs were removed, weighted and percentage of radioactivity/gram calculated. Result: In the in vitro experiment, the radioactivity on blood cells compartment and on insoluble fractions of plasma was diminished. The shape and the perimeter/area ratio of the RBC were altered in in vitro assays. An increase of the percentage of radioactivity of Na99mTcO4 was observed in stomach after in vivo treatment. Conclusion: These results could be due to substances of the CE or by the products of the metabolism of this extract in the animal organism. These findings are examples of drug interaction with a radiopharmaceutical, which could lead to misdiagnosis in clinical practice with unexpected consequences. PMID:24143045

  3. Development of a lyophilized formulation for preparing the radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20; Desarrollo de una formulacion liofilizada para la preparacion del radiofarmaco {sup 177}-DOTA-Anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Serrano E, L. A.

    2015-07-01

    The radiolabeled proteins are molecules of interest in nuclear medicine for their diagnostic and therapeutic application in cancer. Antibodies, such as chimeric monoclonal antibody Anti-CD20 rituximab, have established themselves as suitable vectors of radionuclides (e.g. {sup 177}Lu) , introducing high affinity by the surface antigens over- expressed and widely distributed in cells involved in certain diseases. The aim of this work was to design, optimize and document the production process of radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20 for sanitary registration request to the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). First, a raw material analysis using the Ft-Mir technique and gamma spectrometry was performed. Then, was carried out the development of the lyophilized formulation for the preparation of {sup 177}Lu-DOTA-Anti-CD20, in which an ANOVA was performed where the dependent variable was the radiochemical purity. The optimal pharmaceutical formulation was: 5 mg DOTA-CD20 and 80 mg Mannitol to be reconstituted with 1 m L of acetate buffer 0.25 M, ph 7, with an incubation time of 15 min at 37 degrees Celsius in a dry bath. Once completed the development of the lyophilized formulation, we proceeded to the optimization of the production process, development and validation of the analytical method. Three batches were prepared under protocols of Good Manufacturing Practice, which met pre-established specifications as sterile and endotoxin-free of bacterial formulations, with greater that 95% of radiochemical purity. Currently, is conducting the study of shelf stability. Upon completion of the stability studies, the legal record of {sup 177}Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

  4. Steroids Update, Part 1 and Part 2.

    Science.gov (United States)

    Miller, Calvin; Duda, Marty

    1986-01-01

    Part 1 of this two-part article describes the views of a physician who believes that athletes who want to take steroids are best protected by receiving a prescription and monitoring. Part 2 discusses the more general view of physicians that steroids should not be prescribed but perhaps should be monitored. (MT)

  5. Evaluation of a group of health professionals on the physics and toxicological concepts of the radiopharmaceuticals that uses {sup 123}I e {sup 131}I radioisotopes; Avaliacao de um grupo de profissionais de saude sobre os conceitos fisicos e toxicologicos dos radiofarmacos que utilizam os radioisotopos {sup 123}I e {sup 131}I

    Energy Technology Data Exchange (ETDEWEB)

    Luiz, L.C. [Faculdade Bezerra de Araujo (FABA), Rio de Janeiro, RJ (Brazil); Universidade do Estado do Rio de Janeiro (DFAT-UERJ), RJ (Brazil). Inst. de Fisica Armando Dias Tavares; Brandao, D.L. [Faculdade Bezerra de Araujo (FABA), Rio de Janeiro, RJ (Brazil); Batista, R.T., E-mail: leandro.dfnae@bol.com.br, E-mail: brandao.dl@oi.com.br, E-mail: batistartb@hotmail.com [Universidade do Estado do Rio de Janeiro (DFAT-UERJ), RJ (Brazil). Inst. de Fisica Armando Dias Tavares

    2011-07-01

    In order to evaluate the level of knowledge of a group of health professionals in the area west of the city of Rio de Janeiro, a survey of nurses, nursing technicians, doctors and graduate students in pharmacy, concerning production, radiation emitted, applications and toxicities of radiopharmaceuticals using {sup 123}I radioisotopes and {sup 131}I. These radioisotopes are widely used in Nuclear Medicine to aid in the diagnostic imaging and therapeutic procedures. In this paper is presented an approach on radiopharmaceuticals using radioisotopes mentioned above so that it has knowledge of what was asked to group of professionals here. With this work, it is expected to contribute to the knowledge of these professionals, as well as the general public, in Nuclear Physics and radiation protection concepts for the subject in question. (author)

  6. Preparation of the radiopharmaceutical {sup 99m} Tc-HYNIC-cyclo-Lys-D-Phe-RGD for In vivo image of integrines; Preparacion del radiofarmaco {sup 99m} Tc-HYNIC-ciclo-Lys-D-Phe-RGD para imagen In vivo de integrinas

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez H, E. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico)

    2007-07-01

    The diagnostic of some pathological processes by means of images constitutes one of the used methods in the determination of the origin, condition and/or evolution of one illness. The use of contrast agents in conjunction with other techniques help to the obtaining and visualization of complex systems, among these we can find to those radiopharmaceuticals used in nuclear medicine to visualize diverse organs and corporal systems. At the moment it is sought to develop a radiopharmaceutical of third generation that can be used for image In vivo of integrines with the purpose of detecting angio genesis processes, that which would allow to diagnose in way it specifies a wide range of primary tumors and their metastasis. Presently work it developed the radiopharmaceutical {sup 99m}Tc-HYNIC-cycle-Lys-D-Phe-RGD, likewise the good conditions were determined for the formation of this complex. The HYNIC was employee as chelating agent, using as co ligands EDDA and Tricine for to complete the sphere of coordination of the {sup 99m}Tc. The conjugated HYNIC-RGD was synthesized, purified, characterized and radiolabelled In situ with {sup 99m}Tc using High pressure liquid chromatography as analysis method in Reverse Phase (RP-HPLC). By this way it was developed the lyophilized formulation for its instantaneous labelled to which were carried out quality control tests. The one conjugated was obtained free of impurities, showing stability at same as their complex formed with {sup 99m}Tc. The analysis method was validated turning out to be necessary, exact, lineal and specific for the quantification of the analyte of interest. The lyophilized formulation showed a radiochemical purity bigger than 95%, besides being sterile and free of pyrogens. The biodistribution tests in athymic mice with induced tumors showed that the radiopharmaceutical was united mainly to the tumor and that this it was excreted mainly for renal via. (Author)

  7. Internal dosimetry of radiopharmaceuticals derived of antitumor polypeptide isolated from venoms: Crotalus durissus terrifucus and Scorpaena plumieri;Dosimetria interna de radiofarmacos derivados de polipeptideos antitumorais isolados dos venenos de: Crotalus durissus terrificus e Scorpaena plumieri

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Henrique Martins de

    2009-07-01

    The identification of new diagnostic and therapeutic agents capable of inhibiting tumor growth is essential for improving the prognosis of patients suffering from malignant tumors (glioma, breast and others). In this context, natural products (plants and animals) are a rich source of substances with potential antitumor. Despite knowledge of the etiology and pathology of tumors little progress has been observed in the area of diagnosis. Molecules of snake venoms have been shown to play an important role not only in the survival and proliferation of tumor cells but also in the process of tumor cell adhesion, migration and angiogenesis. Polypeptides isolated from the venom of the snake, Crotalus durissus terrificus, Crtx, and Scorpaena plumieri fish, SPGP, have antitumor activity against malignant tumors. It was shown that similar radio iodines Crtx and SPGP, {sup 125}I-Crtx and {sup 125}I-SPGP, can interact specifically with malignant tumors and induce cell death. Prototype-based radiopharmaceuticals Crtx and SPGP containing radioiodine 1311 were able to produce diagnostic images to accumulate specifically in the tumor site. The present study aimed at evaluating the potential radiological safety and diagnostic/therapeutic efficacy of {sup 131}I-Crtx {sup l31}I-SPGP and (evaluated from the biokinetic data in mice bearing Ehrlich tumor) were treated by the MIRD formalism to carry out internal dosimetry studies. Absorbed doses due to the uptake of {sup 131}I-Crtx and {sup 131}I-SPGP were determined in various organs of mice and implanted into the tumor. The results obtained for the animal model were extrapolated to humans by assuming a similar concentration ratio among the various tissues between mice and humans. In extrapolation, we used the masses of human organs of the phantom of Cristy/Eckerman. Both radiation penetrating and non penetrating of {sup 131}I on the tissue were considered in dose calculations. The absorbed dose in the bone marrow due to the

  8. Development and validation of methodology for technetium-99m radiopharmaceuticals using high performance liquid chromatography (HPLC); Desenvolvimento e validacao de metodologia para radiofarmacos de tecnecio-99m empregando cromatografia liquida de alta eficiencia (CLAE)

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Erika Vieira de

    2009-07-01

    Radiopharmaceuticals are compounds, with no pharmacological action, which have a radioisotope in their composition and are used in Nuclear Medicine for diagnosis and therapy of several diseases. In this work, the development and validation of an analytical method for {sup 99}mTc-HSA, {sup 99}mTc-EC, {sup 99}mTc-ECD and {sup 99}mTc-Sestamibi radiopharmaceuticals and for some raw materials were carried out by high performance liquid chromatography (HPLC). The analyses were performed in a Shimadzu HPLC equipment, LC-20AT Prominence model. Some impurities were identified by the addition of a reference standard substance. Validation of the method was carried out according to the criteria defined in RE n. 899/2003 of the National Sanitary Agency (ANVISA). The results for robustness of the method showed that it is necessary to control flow rate conditions, sample volume, pH of the mobile phase and temperature of the oven. The analytical curves were linear in the concentration ranges, with linear correlation coefficients (r{sup 2}) above 0.9995. The results for precision, accuracy and recovery showed values in the range of 0.07-4.78%, 95.38-106.50% and 94.40-100.95%, respectively. The detection limits and quantification limits varied from 0.27 to 5.77 {mu}g mL{sup -1} and 0.90 to 19.23 {mu}g mL{sup -1}, respectively. The values for HAS, EC, ECD and MIBI in the lyophilized reagents were 8.95; 0.485; 0.986 and 0.974 mg L-1, respectively. The mean radiochemical purity for {sup 99}mTc-HSA, {sup 99}mTc-EC, {sup 99}mTc-ECD and {sup 99}mTc-Sestamibi was (97.28 {+-} 0.09)%, (98.96 {+-} 0.03)%, (98.96 {+-} 0.03)% and (98.07 {+-} 0.01)%, respectively. All the parameters recommended by ANVISA were evaluated and the results are below the established limits. (author)

  9. Parts, Axial Parts, and Next Parts in Kannada

    Directory of Open Access Journals (Sweden)

    R. Amritavalli

    2007-12-01

    Full Text Available Nouns meaning ‘place, region’ and ‘part’ are compounded in Kannada with a `bleached’ noun (a putative postposition to form AxPart and Part readings. As in other languages, the AxPart or ‘region’ reading does not pluralize, does not permit adjectival modification, and allows for MeasureP modification (unlike the part reading. AxParts may also be formed out of nouns by the fusion of a dative marker or a genitive marker with the N; these case markers introduce the Place element. The dative case may be optionally overt (e.g. pakka-kke ‘side-dative,’ ‘to a side’, or covert (in AxParts like munde ‘front’. The genitive marker gives a sense of immediate adjacency that we designate the NextPart reading. Interestingly, the dative and genitive cases in Kannada also allow nouns to assume the function of predicative and attributive adjectives.

  10. Development of a lyophilized formulation for the preparation of radiopharmaceutical {sup 68}Ga-DOTA-E-[c(RGDfK)]{sub 2} for the diagnosis of breast cancer tumors; Desarrollo de una formulacion liofilizada para la preparacion del radiofarmaco {sup 68}Ga-DOTA-E-[c(RGDfK)]{sub 2} para el diagnostico de tumores de cancer de mama

    Energy Technology Data Exchange (ETDEWEB)

    Terron A, E. J.

    2015-07-01

    Radiopharmaceuticals of third generation by its design that includes peptides capable of selectively directing the radiation to a specific molecular target are useful in molecular medicine for obtaining molecular images that allow recording in vivo phenomena temporal-space of molecular or cellular processes, with diagnostic or therapeutic applications. Generally, peptides that recognize cellular receptors that are over-expressed in cancer cells of interest are used; such is the case of RGD (arginine-glycine-aspartic acid) a tri-peptide sequence which recognizes to the membrane receptors α(v)β(3) and α(v)β(5) that are involved in metastasis and angiogenic processes as well as in tumor cells of breast glioma. The high affinity and selectivity of RGD peptide with integrin s α(v)β(3) and α(v)β(5) is the basis for designing radiopharmaceuticals for diagnostic of breast cancer and the metastasis and angiogenic processes. In this paper a useful lyophilized formulation was development for obtaining {sup 68}Ga-DOTA-E-[c(RGDfK)]{sub 2} radiopharmaceutical that for its effectiveness, stability and security can be used in humans. The production process of core-equipment DOTA-E-[c(RGDfK]{sub 2}/Buffer sodium acetate 1.0 M was optimized, and the formulation was transferred to the radiopharmaceuticals production plant of the Instituto Nacional de Investigaciones Nucleares (ININ). The optimized formulation of the core-equipment for the {sup 68}Ga-DOTA-E-[c(RGDfK)]{sub 2} radiopharmaceutical preparation is: DOTA-E-[c(RGDfK)]{sub 2} peptide - 75 μg; Mannitol - 50 mg; Sodium acetate - 14 mg; Sodium acetate buffer 1.0 M ph 4.3 - 0.5 m L. The production process was validated and stability studies were carried out to the validation batches in compliance with the validation master plan of the ININ and in adherence to compliance of the applicable national and international regulations. Also the legal dossier was drawn up in order to make the application of sanitary registration

  11. Design and optimization of the production process of radiopharmaceutical {sup 177}Lu-DOTA-Nal{sup 3}-Octreotide for the treatment of gastro-entero-pancreatic tumors; Diseno y optimizacion del proceso de produccion del radiofarmaco {sup 177}Lu-DOTA-Nal{sup 3}-Octreotido para el tratamiento de tumores gastroenteropancreaticos

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez G, M. F.

    2013-07-01

    The radiolabel peptides are molecules of interest in nuclear medicine for their therapeutic and diagnostic application in cancer. Among an impressing group of relevant peptides, those similar of the somatostatin, as the Nal{sup 3}-Octreotide (NOC), have established as potential radiopharmaceuticals when presenting significant affinity for the receptors of this peptide hormone that are over expressed and broadly distributed in tumors of neuroendocrine origin, as the gastro-entero-pancreatic tumors. On the other hand, the Lutetium-177 ({sup 177}Lu) is an ideal candidate for the peptides radiolabel and has favorable characteristics to be used in radionuclide therapy. The objective of this work was designing, optimizing and to document the production process of the radiopharmaceutical {sup 177}Lu-DOTA-Nal{sup 3}-Octreotide ({sup 177}Lu-DOTANOC) for the solicitude of its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS). For the optimization of the production process a factorial design of three variables was evaluated with mixed levels (18 combinations), where the dependent variable is the radiochemical purity and the analytic method used to determine this parameter (High Performance Liquid Chromatography) was validated. Later on, by means of the production of 3 lots of the optimized formula of the radiopharmaceutical {sup 177}Lu-DOTANOC the production process was validated and the stability long term study to determine the period of useful life was carried out. The following pharmaceutical formulation was adopted as good: 1.85 GBq (0.5μg) of {sup 177}Lu, 250 μg of DOTANOC and 150 μL of acetates Buffer 1 M ph 5 in 5 m L of the medium. The analytic method used to determine the radiochemical purity of the formulation satisfied the requirements for the wished analytic application. We can conclude that the 3 validation lots prepared under protocols of Good Production Practices, in the Plant of Radiopharmaceuticals Production of the

  12. The first experience of using {sup 99m}Tc-Al{sub 2}O{sub 3}-based radiopharmaceutical for the detection of sentinel lymph nodes in cervical cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Sinilkin, I. G.; Chernov, V. I.; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L. [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050 (Russian Federation); Lyapunov, A. Yu., E-mail: Lyapunov1720.90@mail.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); Kolomiets, L. A. [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Moskovsky Trakt 2, Tomsk, 634050 (Russian Federation)

    2016-08-02

    The purpose of the study was to evaluate the feasibility of using {sup 99m}Tc-Al{sub 2}O{sub 3}-based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (T1aNxMx-T2bNxMx) treated at the Tomsk Cancer Research Institute. In the 18 hours before surgery, 80 MBq of the {sup 99m}Tc-Al{sub 2}O{sub 3} in peritumoral injected, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3 (the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac (14%), obturator (14%), presacral and retrosacral regions (14%), and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  13. Sentinel lymph node identification in breast cancer using periareolar and subdermal injection of the radiopharmaceutical in four points; Identificacao do linfonodo sentinela no cancer de mama com injecao subdermica periareolar em quatro pontos do radiofarmaco

    Energy Technology Data Exchange (ETDEWEB)

    Coelho-Oliveira, Afranio; Rocha, Augusto Cesar Peixoto [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Ginecologia]. E-mail: afranioliveira@hotmail.com; Gutfilen, Bianca; Pessoa, Maria Carolina Pinheiro; Fonseca, Lea Mirian Barbosa da [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia e Medicina Nuclear

    2004-08-01

    The aim of this study was to identify the sentinel node by periareolar injection of the radiopharmaceutical in four points, regardless of tumor topography. The sentinel node biopsy reduces morbidity in axillary staging. Fifty-seven sentinel node biopsies were prospectively performed in two groups: group A (25 patients) and group B (32 patients). The peritumoral injection technique was used in group A and the new injection technique in four points was used in group B. The sentinel node biopsies were studied by imprint cytology and hematoxylin and eosin staining followed by axillary lymph node dissection in all patients of group A and only in the positive cases of group B. In group A, 88% (22/25) of the sentinel nodes were identified. There was no false negative case; the sensibility and specificity were of 100%. In group B, 96% (31/32) of sentinel nodes were identified and the status of the axillary lymph nodes showed a predictive positive value of 100%. The number of sentinel nodes varied from 1 to 7, mode of 1 and median of 2.7. The hotspot area was 10 to 100 times the background radiation. The periareolar injection in four points seems to be a good lymphatic mapping method for identification of the sentinel node. We suggest the standardization of this site for injections to identify the sentinel node, although further studies to confirm these findings are necessary. (author)

  14. Part C and Part D Compliance Actions

    Data.gov (United States)

    U.S. Department of Health & Human Services — This page includes results from CMSs Past Performance Review. The report called Spring 2014 Past Performance Review Outlier Results lists MA organizations and Part D...

  15. A new strategy for the preparation of peptide-targeted technetium and rhenium radiopharmaceuticals. The automated solid-phase synthesis, characterization, labeling, and screening of a peptide-ligand library targeted at the formyl peptide receptor.

    Science.gov (United States)

    Stephenson, Karin A; Banerjee, Sangeeta Ray; Sogbein, Oyebola O; Levadala, Murali K; McFarlane, Nicole; Boreham, Douglas R; Maresca, Kevin P; Babich, John W; Zubieta, Jon; Valliant, John F

    2005-01-01

    A new solid-phase synthetic methodology was developed that enables libraries of peptide-based Tc(I)/Re(I) radiopharmaceuticals to be prepared using a conventional automated peptide synthesizer. Through the use of a tridentate ligand derived from N-alpha-Fmoc-l-lysine, which we refer to as a single amino acid chelate (SAAC), a series of 12 novel bioconjugates [R-NH(CO)ZLF(SAAC)G, R = ethyl, isopropyl, n-propyl, tert-butyl, n-butyl, benzyl; Z = Met, Nle] that are designed to target the formyl peptide receptor (FPR) were prepared. Construction of the library was carried out in a multiwell format on an Advanced ChemTech 348 peptide synthesizer where multi-milligram quantities of each peptide were isolated in high purity without HPLC purification. After characterization, the library components were screened for their affinity for the FPR receptor using flow cytometry where the K(d) values were found to be in the low micromolar range (0.5-3.0 microM). Compound 5j was subsequently labeled with (99m)Tc(I) and the product isolated in high radiochemical yield using a simple Sep-Pak purification procedure. The retention time of the labeled compound matched that of the fully characterized Re-analogue which was prepared through the use of the same solid-phase synthesis methodology that was used to construct the library. The work reported here is a rare example of a method by which libraries of peptide-ligand conjugates and their rhenium complexes can be prepared.

  16. Fragmentation of Nimotuzumab for Preparation of 125I-F(ab’2-Nimotuzumab as a Precursor for Preparing 125I-F(ab’2-Nimotuzumab-NLS Radiopharmaceutical for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    R.D. Haryuni

    2014-04-01

    Full Text Available Nimotuzumab is an anticancer agent which belongs to the inhibitor group of Epidermal Growth Factor Receptor (EGFR. This monoclonal antibody has a relatively high molecular weight which makes slow penetration on tumor cell, as concequence, it is less attractive in imaging kinetics, and potentially elicits antibodies respons. Therefore in this study nimotuzumab was fragmented to form bivalent antibody [F(ab’2] and then labeled with 125I to form 125I-F(ab’2-nimotuzumab which can be used further as a precursor for preparing 125I-F(ab’2-nimotuzumab-NLS (NLS = nuclear localizing sequences radiopharmaceutical for radioimmunotherapy. The aims of this study were to obtain characteristics of 125I-F(ab’2-nimotuzumab by comparing with the 125I labeled-intact nimotuzumab (125I-nimotuzumab. This study was initiated by purifying nimotuzumab by mean of dialysis. The purified nimotuzumab was then fragmented by using pepsin. The F(ab'2-nimotuzumab formed was then purified from its by-products which formed in fragmentation process by using a PD-10 column (consisted Sephadex G25. The intact nimotuzumab and its F(ab’2 fragment were then labeled with the 125I to form 125I-nimotuzumab and 125I-F(ab’2-nimotuzumab. The radiochemical purity are 98.27 % and 93.24 % ,respectively. Stability test results show that, both of 125I-nimotuzumab and 125I-F(ab’2-nimotuzumab more stable at 4 °C than at room temperature storage and 37 °C

  17. Binding of ReO[subscript 4];#8722; with an engineered MoO[subscript 4 superscript 2];#8722;-binding protein: towards a new approach in radiopharmaceutical applications

    Energy Technology Data Exchange (ETDEWEB)

    Aryal, Baikuntha P.; Brugarolas, Pedro; He, Chuan (UC)

    2012-05-25

    Radiolabeled biomolecules are routinely used for clinical diagnostics. {sup 99m}Tc is the most commonly used radioactive tracer in radiopharmaceuticals. {sup 188}Re and {sup 186}Re are also commonly used as radioactive tracers in medicine. However, currently available methods for radiolabeling are lengthy and involve several steps in bioconjugation processes. In this work we present a strategy to engineer proteins that may selectively recognize the perrhenate (ReO{sub 4}{sup -}) ion as a new way to label proteins. We found that a molybdate (MoO{sub 4}{sup 2-})-binding protein (ModA) from Escherichia coli can bind perrhenate with high affinity. Using fluorescence and isothermal titration calorimetry measurements, we determined the dissociation constant of ModA for ReO{sub 4}{sup -} to be 541 nM and we solved a crystal structure of ModA with a bound ReO{sub 4}{sup -}. On the basis of the structure we created a mutant protein containing a disulfide linkage, which exhibited increased affinity for perrhenate (K{sub d} = 104 nM). High-resolution crystal structures of ModA (1.7 {angstrom}) and A11C/R153C mutant (2.0 {angstrom}) were solved with bound perrhenate. Both structures show that a perrhenate ion occupies the molybdate binding site using the same amino acid residues that are involved in molybdate binding. The overall structure of the perrhenate-bound ModA is unchanged compared with that of the molybdate-bound form. In the mutant protein, the bound perrhenate is further stabilized by the engineered disulfide bond.

  18. Effect of the peptide Tat(49-57) on the bio-distribution and similar radiopharmaceuticals dosimetry of the bombesin; Efecto del peptido TAT(49-57) sobre la biodistribucion y dosimetria de radiofarmacos analogos de la bombesina

    Energy Technology Data Exchange (ETDEWEB)

    Santos C, C. L.

    2011-07-01

    The gastrin-releasing peptide receptor (GRP-r) is over-expressed in prostate and breast cancer. {sup 99m}Tc-Bombesin ({sup 99m}Tc-Bn) has been reported as a radiopharmaceutical with specific cell GRP-r binding. The HIV Tat(49-57)-derived peptide has been used to deliver a large variety of molecules to cell nuclei. New hybrid radiopharmaceuticals of type {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn ({sup 99m}Tc-Tat-Bn) and {sup 188}Re-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn ({sup 188}Re-Tat-Bn), would increase cell uptake and internalized in cancer cell nuclei could act as an effective system of targeted radiotherapy using Auger and internal conversion (I C) electron emissions near DNA. The aim of this research was to prepare and assess in vitro and in vivo uptake kinetics in cancer cells of {sup 99m}Tc/{sup 188}Re-Tat-Bn and the in vitro nucleus and cytoplasm internalization kinetics in GRP receptor-positive cancer cells as well as to evaluate the subcellular-level radiation absorbed dose associated with the observed effect on cancer cell DNA proliferation. Structures of N{sub 2}S{sub 2}-Tat-Bn and Tc/Re(O)N{sub 2}S{sub 2}-Tat-Bn were calculated by an Mm procedure. {sup 99m}Tc-Tat-Bn and {sup 188}Re-Tat-Bn were synthesized and stability studies carried out by HPLC and I TLC-Sg analyses in serum and cysteine solutions. In vitro internalization was tested using human prostate cancer Pc 3 cells and breast carcinoma cell lines MDA-Mb 231 and MCF 7. Nuclei from cells were isolated using a nuclear extraction kit. Total disintegrations in each subcellular compartment were calculated by integration of experimental time activity kinetic curves. Nucleus internalization was corroborated by con focal microscopy images using immunofluorescent labelled Tat-Bn. Biodistribution was determined in Pc 3 tumor-bearing nude mice. The Penelope code was used to simulate and calculate the absorbed dose by contribution of {beta}, Auger and I C electrons in the cytoplasm and

  19. Obtaining a metastasis model in vivo for the evaluation of the radiopharmaceuticals sensitivity labeled with {sup 99m}Tc; Obtencion de un modelo de metastasis in vivo para la evaluacion de la sensibilidad de radiofarmacos marcados con {sup 99m}Tc

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez A, V. M.

    2015-07-01

    Nuclear medicine currently has a wide range of techniques that support the diagnosis of various diseases, including cancer that prevails as the most important. In the present research work was proposed to develop a model that would study the process known as metastasis, because this process is vital because most of the deaths in patients with some form of cancer are caused by metastasis. The objective was to obtain an in vivo model of metastasis induced with AR42J cells for studying the radiopharmaceuticals sensitivity labeled with {sup 99m}Tc. To achieve the objective proposed a study model in which it could make a real time evaluation of some radiopharmaceuticals with reported efficiency was development, in order to determine their sensitivity in similar conditions to the metastasis process. This required a mouse model that was used to observe a similar process to metastasis, inducing cells of the AR42J cell line, since these cells have good proliferation and have molecular targets for a minimum of 3 standardized radiopharmaceuticals. Was elected radionuclide {sup 99m}Tc, because of its low emission of radiation into the tissues, besides having a half life of 6 hours and provides a good visualization of anatomical structures. On the other hand the stable expression of green fluorescent protein in tumor cells appears to be a suitable tool for the detection of cancer development in early stages and the formation of in vivo micro metastases, so two fluorescence tests were performed and other by electrophoresis. The results showed that both study models can be carried out without increasing complexity and meeting the expectations expected for which they were designed. (Author)

  20. Development of a lyophilized formulation for preparing the radiopharmaceutical {sup 68}Ga-DOTA-Nal{sup 3}-Octreotide for the diagnosis of tumors of neuroendocrine origin; Desarrollo de una formulacion liofiizada para la preparacion del radiofarmaco {sup 68}Ga-DOTA-Nal{sup 3}-Octreotido para el diagnostico de tumores de origen neuroendocrino

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzo L, G. A.

    2015-07-01

    The present study aimed to develop a radiopharmaceutical consisting of an emitter positrons radionuclide ({sup 68}Ga) which is used in imaging by positron emission tomography; and a peptide capable of binding to somatostatin receptors subtypes 2, 3 and 5; which together serve as a diagnostic support of tumors of neuroendocrine origin. The peptide characterization DOTA-1-Naphthylalanine{sup 3}-Octreotide (DOTA-NOC) by infrared spectroscopy technique by Fourier transform was performed, in which the principal functional groups belonging to this molecule were identified as well as its identification by UV-Vis spectroscopy. Subsequently, a variance analysis taking into account three different levels of amounts of sodium acetate, and three different levels of amounts of the peptide was performed. These masses were subjected to lyophilization for a period of 21 h; after completion of lyophilization, were labeled with 2 m L of {sup 68}GaCl{sub 3} eluates of a {sup 68}Ge/{sup 68}Ga ITG generator to determine the percentage of radiochemical purity of the different formulations. It was observed that the ideal formulation must contain 75 μg of peptide and 14 mg of NaOAc, according to studies, was determined that the amount of peptide does not influence the response of radiochemical purity in the same way that the amount of added sodium acetate, which produces different effects on the dependent variable. Finally the radiopharmaceutical formulation was obtained with greater than 95% of radiochemical purity. The validation of the analytical method was performed describing the system accuracy and linearity, specificity and accuracy; linearity and precision of the method, taking into account acceptance criteria based on the guidance of validation of analytical methods published by the National Association of Pharmacists Chemical Biologists of Mexico, A. C.; the parameters evaluated met the specifications given by the guide validation of analytical methods. Uptake and

  1. Standard biological parts knowledgebase.

    Science.gov (United States)

    Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M; Gennari, John H

    2011-02-24

    We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  2. Standard biological parts knowledgebase.

    Directory of Open Access Journals (Sweden)

    Michal Galdzicki

    2011-02-01

    Full Text Available We have created the Knowledgebase of Standard Biological Parts (SBPkb as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org. The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org. SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL, a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  3. 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.

  4. 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.

  5. Introduction to Part 3

    DEFF Research Database (Denmark)

    Petersen, Nils Holger

    2015-01-01

    A brief contextualising discussion of Western Music History and its relations to Theological Aesthetical Thought since Carolingian Times as an introduction to 3 music articles in Part 3 of the volume.......A brief contextualising discussion of Western Music History and its relations to Theological Aesthetical Thought since Carolingian Times as an introduction to 3 music articles in Part 3 of the volume....

  6. Play your part

    CERN Document Server

    Ramsey, Gaynor

    1978-01-01

    Play your part is a collection of then situations in which students have to take on the roles of particular people and express their opinions, feelings or arguments about the situation. Play your part is intended for use with advanced students of English.

  7. Partly occupied Wannier functions

    DEFF Research Database (Denmark)

    Thygesen, Kristian Sommer; Hansen, Lars Bruno; Jacobsen, Karsten Wedel

    2005-01-01

    We introduce a scheme for constructing partly occupied, maximally localized Wannier functions (WFs) for both molecular and periodic systems. Compared to the traditional occupied WFs the partly occupied WFs possess improved symmetry and localization properties achieved through a bonding-antibondin...

  8. Evaluation of the internalization kinetics of the radiopharmaceutical {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)Lys{sup 3}-Bn with diagnostic purposes, using comet assay; Evaluacion de la cinetica de internalizacion del radiofarmaco {sup 99m}Tc-N{sub 2}S{sub 2}-TAT(49-57)Lys{sup 3}-BN con fines diagnosticos, empleando ensayo cometa

    Energy Technology Data Exchange (ETDEWEB)

    Luna G, M. A.

    2011-07-01

    Gastrin-rea leasing peptide receptors (GRP-r) are over expressed in breast and prostate cancer cells. Bombesin (Bn) binds specifically and strongly to GRP-r and this is the base for to label the Bn with radionuclides by gamma rays. Tat (49-57) is a peptide that across the cell membrane easily so that, when it is conjugated to different proteins, it can works as a Trojan horse, facilitating the drug internalization to the cells. The radiopharmaceutical {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn was prepared for diagnosis and therapy at early stage of breast cancer. The objective of this study was to determine the role of Tat in the internalization kinetics of radiopharmaceuticals measured by DNA damage induced by means of comet assay. Human lymphocytes were treated with the following protocols: a) Tat-Bn, b) {sup 99m}Tc-Bn, or c) {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn, also an untreated group was conformed. The internalization was evaluated at 0, 5, 10, 15, 30 and 60 min after exposure with three repetitions each one, and for radiopharmaceuticals with 2.9, 6.6, 9.0 and 14.8 MBq activities. DNA damage was scored in 100 cells per time and treatment, as tail length and tail moment. A Kruskal-Wallis variance analysis with p{<=} 0.05 was applied for comparison between treatments. The results showed that the damage caused by {sup 99m}Tc-N{sub 2}S{sub 2}-Tat(49-57)-Lys{sup 3}-Bn is significantly higher than that caused by {sup 99m}Tc-Bn and Tat-Bn, showing that Tat favors the internalization of the radiopharmaceutical. (Author)

  9. The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter Tin-117m

    Directory of Open Access Journals (Sweden)

    Suresh C. Srivastava

    2007-09-01

    Full Text Available A variety of radionuclides continue to be investigated and/or clinically used for different therapeutic applications in nuclear medicine. The choice of a particular radionuclide with regard to appropriate emissions, linear energy transfer (LET, and physical half-life, etc., is dictated to a large extent by the character of the disease (e.g., solid tumor or metastatic disease, and by the carrier to selectively transport the radionuclide to the desired site. An impressive body of information has appeared in the recent literature that addresses many of these considerations. This article summarizes and discusses the role of high-LET electron emitters and their advantage in the treatment of cancer or for other disorders in specific situations. Areas such as bone pain palliation, bone malignancy therapy, and radiation synovectomy are covered in greater detail. Projections are made as to the future directions and progress in these areas. A discussion of the various issues related to the selection criteria that are useful for choosing the appropriate radionuclide for a particular application is included. Use of high-LET electron emitters is discussed in greater detail, with particular emphasis on the use of conversion electron emitter tin-117m for various therapeutic applications.Uma variedade de radionuclídeos continua a ser investigada e/ou clinicamente utilizada para diferentes aplicações terapêuticas em medicina nuclear. A escolha de um radionuclídeo, considerando-se sua emissão apropriada, transferência linear de energia (LET e meia-vida física é determinada na maior parte pelo caráter da doença (p.ex., tumor sólido ou doença metastática, e pelo carreador que transporta o radionuclídeo seletivamente para o sítio desejado. Um notável conjunto de informações voltadas para essas considerações tem aparecido na literatura recente. Esse trabalho resume e discute o papel de emissores de elétrons de alta-LET e sua vantagem no

  10. Biotechnological application of protein Leuc-B isolated from Bothrops leucurus venom as a prototype for antitumoral radiopharmaceutical;Aplicacao biotecnologica da proteina Leuc-B isolada da peconha de Bothrops leucurus como prototipo de radiofarmaco antitumoral

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Lucilene Marcia

    2010-07-01

    solution and acridine/ethidium bromide indicate that the antitumoral effect of these substances occurs via apoptosis. Radioactive probes of Leuc-B ({sup 131}/{sup 125}I-Leuc-B) were synthesized with high specific activity and high radiochemical purity. Biodistribution studies, performed by intravenous injection and intratumoral flow in mice bearing Ehrlich tumor showed a significant tumor uptake Leuc-B ( p <0.05). These results show the potential of Leuc-B as a template for the development of drugs and radiopharmaceuticals for diagnosis and therapy of tumors. (author

  11. Development of methodologies for internal exposure assessment due to the radiopharmaceutical {sup 18}FDG; Desenvolvimento de metodologias para avaliacao da exposicao ocupational interna devido ao radiofarmaco {sup 18}FDG

    Energy Technology Data Exchange (ETDEWEB)

    Lacerda, Isabelle Viviane Batista de

    2013-07-01

    The production of {sup 18}F has increased in the last decade. It is produced basically for the synthesis of {sup 18}F- fluorodeoxyglucose ({sup 18}FDG), the main radiopharmaceutical used in PET (Positron Emission Tomography) scans. The growth in the frequency of these tests resulted in rise of the number of occupationally exposed individuals (OEI) to the radionuclide {sup 18}F as {sup 18}FDG, increasing thereby the probability of its accidental incorporation. This study aimed to implement optimized techniques for assessing internal exposures of individuals occupationally exposed through both in vivo and in vitro bioassay methods during production and handling of {sup 18}FDG at the Divisao de Producao de Radiofarmacos (DIPRA), Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN). The in vivo monitoring was conducted at the Laboratorio de Dosimetria Interna, Divisao de Laboratorios Tecnico-Cientificos (DILAB). For this bioassay method, measurements were done with a 3x3' NaI(Tl) scintillation detector coupled to Genie 2000 software. The calibration of the system was performed with a brain phantom containing a standard liquid source of {sup 22}Na to simulate a contaminated individual. The calibration of the HPGe coaxial detector for in vitro monitoring was performed at the Laboratorio de Medidas de Atividade de Radionuclideos (DIPRA/CRCN-NE/CNEN) with a standard source of {sup 22}Na. Base on the calibration factors, it was possible to determine the minimum detectable activities (MDA) for the systems by using direct measurements and simulation of uncontaminated urine. Then, through the biokinetic models published by ICRP 106 and edited by the AIDE software (version 6.0), it was possible to estimate the minimum detectable effective dose (MDED), which evaluates the detection sensitivity of the techniques developed. The MDED was estimated for in vivo and in vitro measurements performed 2.4 hours after the occurrence of incorporation by ingestion, since

  12. Synthesis, characterization and biological evaluation of [{sup 188}Re(N)(cys{approx})(PNP)]{sup +/0} mixed-ligand complexes as prototypes for the development of {sup 188}Re(N)-based target-specific radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Thieme, Stefan [Institute of Radiopharmacy, Forschungszentrum Dresden Rossendorf, P.O. Box 510 119, 01314 Dresden (Germany); Agostini, Stefania [Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova (Italy); Bergmann, Ralf; Pietzsch, Jens; Pietzsch, Hans-Juergen [Institute of Radiopharmacy, Forschungszentrum Dresden Rossendorf, P.O. Box 510 119, 01314 Dresden (Germany); Carta, Davide; Salvarese, Nicola [Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova (Italy); Refosco, Fiorenzo [ICIS-CNR, Corso Stati Uniti 4, 35127 Padova (Italy); Bolzati, Cristina, E-mail: bolzati@icis.cnr.i [Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova (Italy); ICIS-CNR, Corso Stati Uniti 4, 35127 Padova (Italy)

    2011-04-15

    We report on an efficient procedure for the preparation of [{sup 188}Re(N)(PNP)]-based complexes (where PNP is diphosphinoamine) useful in the development of target-specific radiopharmaceuticals. The radiochemical yield of the compounds was optimized considering such reaction parameters as nature of the nitrido nitrogen donor, reaction times and pH level. The chemical identity of the {sup 188}Re agents was determined by high-performance liquid chromatography comparison with the corresponding well-characterized cold Re compounds. {sup 188}Re(N) mixed compounds have been evaluated with regard to stability toward transchelation with GSH and degradation by serum enzymes. The clearance of selected radiocompounds from normal tissues and their in vivo stability were evaluated in rats by biodistribution and imaging studies. [{sup 188}Re(N)(cys{approx})(PNP)]{sup +/0} mixed-ligand compounds were efficiently prepared in aqueous solution from perrhenate using a multistep procedure based on the preliminary formation of the labile {sup 188}Re{sup III}-EDTA species, which easily undergo oxidation/ligand exchange reaction to afford the [{sup 188}Re{sup V{identical_to}}N]{sup 2+} core in the presence of dithiocarbazate. The final mixed-ligand compounds were obtained, at 100{sup o}C, by adding the two bidentate ligands to the buffered [{sup 188}Re{sup V{identical_to}}N]{sup 2+} solution (pH 3.2-3.6). However, a relatively high amount of cys{approx} ligand was required to obtain a quantitative radiochemical yield. The complexes were stable toward reoxidation to perrhenate and ligand exchange reactions. In vivo studies showed rapid distribution and elimination of the complexes from the body. No specific uptakes in sensitive tissues/organs were detected. A positive correlation of the distribution of the complexes estimated with biodistribution studies (%ID) and with micro-SPECT semiquantification imaging analysis (standard uptake values) was observed. These results support the

  13. Preparation of the radiopharmaceutical {sup 131}I-Anti-CD20 for the treatment of lymphomas; Preparacion del radiofarmaco {sup 131}I-Anti-CD20 para el tratamiento de linfomas

    Energy Technology Data Exchange (ETDEWEB)

    Pantoja H, I.E

    2004-07-01

    At the present time they are considered to the lymphomas like a problem of first magnitude since has happened it is necessary to be the fifth cancer cause in the world. Different treatments focused to the lymphoma like the chemotherapy and the radiotherapy, have been employees to counteract the No-Hodgkin lymphoma, without these they don't exclude the healthy tissue of the toxicity. It is for it that is taking a new direction with the employment of the directed radioimmunotherapy since this it allows to kill wicked cells selectively with radiation dose joined to the apoptosis and cytotoxicity induced by the own one bio molecule. The radioimmunotherapy with radiolabelled antibodies directed to the surface antigen CD20 represents a new modality for the treatment of No-Hodgkin lymphoma and potentially other illnesses. In this work the parameters of optimization are presented for the preparation, control of quality and evaluation of the stability in vitro and in vivo of the monoclonal antibody anti-CD20 labelled with {sup 131} I for the treatment of No-Hodgkin lymphoma. The anti-CD20 labelled by the chloramine-T method with high radiochemical purity (>98%), it is stable in solution for but of a half life of the radionuclide (8.04 days) The {sup 131} I-anti-CD20 doesn't present dehalogenation in vitro (human serum) during 24 h of incubation at 37 C. According to the tests carried out to establish the immunoreactivity, a percentage of union to cells was obtained (B lymphocytes) bigger to 30%. The biodistribution in mice balb/c one hour after their administration, it shows that there is not high reception in mucous neither kidneys, what indicates that the complex is stable in vivo. In conclusion, the radiopharmaceutical {sup 131} I-anti-CD20 was obtained in sterile injectable solution and free of pyrogens with a radiochemical purity bigger to 98% and a specific activity of 296 MBq. The radiolabelled molecule maintains its biological recognition for the receiving

  14. Male hypogonadism (Part 1

    Directory of Open Access Journals (Sweden)

    Ye.V. Luchytskyy

    2017-05-01

    Full Text Available The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

  15. Walrus parts collection notes

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The attached field diary notes provide documentation of walrus parts collection activities which occurred in the Nome and surrounding area during the periods of May...

  16. HUMAN SPARE PARTS

    National Research Council Canada - National Science Library

    Thomas K. Grose

    2015-01-01

    ... for the fast-growing field of cell-based and personalized therapies, or regenerative medicine, that use cells, either as immunizations or as part of patches and implants, to cure a range of ailments...

  17. Parts lubas uut muusikakooli

    Index Scriptorium Estoniae

    2005-01-01

    Peaminister Juhan Parts vastas Tallinna Muusikakeskkooli õpilase Judith Partsi kirjale Tallinna Muusikakeskkooli olukorrast lubadusega hoida silma peal Tallinna Muusikakeskkoolile, Tallinna Balletikoolile ja Georg Otsa nim. Muusikakoolile ühise hoone võimaldamisest kokkuehituseks Eesti Muusikaakadeemiaga

  18. Matrix comparison, Part 2

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Borlund, Pia

    2007-01-01

    The present two-part article introduces matrix comparison as a formal means for evaluation purposes in informetric studies such as cocitation analysis. In the first part, the motivation behind introducing matrix comparison to informetric studies, as well as two important issues influencing such c...... and Procrustes analysis can be used as statistical validation tools in informetric studies and thus help choosing suitable proximity measures....

  19. Derecho Penal: Parte Especial

    OpenAIRE

    Ríos Corbacho, José Manuel

    2010-01-01

    El objetivo básico que se persigue obtener con el desarrollo de esta asignatura es el conocimiento de la parte especial del Código penal. Se llevará a cabo un análisis individualizado de cada uno de los delitos y faltas, prestando una especial atención a los problemas de parte especial que los mismos plantean. Sobre cada uno de ellos, se analizará la visión jurisprudencial. La asignatura de Derecho penal especial tiene como objetivo enseñar a las/os alumnas/os los delitos y faltas conte...

  20. Plutonium microstructures. Part 1

    Energy Technology Data Exchange (ETDEWEB)

    Cramer, E.M.; Bergin, J.B.

    1981-09-01

    This report is the first of three parts in which Los Alamos and Lawrence Livermore National Laboratory metallographers exhibit a consolidated set of illustrations of inclusions that are seen in plutonium metal as a consequence of inherent and tramp impurities, alloy additions, and thermal or mechanical treatments. This part includes illustrations of nonmetallic and intermetallic inclusions characteristic of major impurity elements as an aid to identifying unknowns. It also describes historical aspects of the increased purity of laboratory plutonium samples, and it gives the composition of the etchant solutions and describes the etching procedure used in the preparation of each illustrated sample. 25 figures.

  1. PHP The Good Parts

    CERN Document Server

    MacIntyre, Peter

    2010-01-01

    Get past all the hype about PHP and dig into the real power of this language. This book explores the most useful features of PHP and how they can speed up the web development process, and explains why the most commonly used PHP elements are often misused or misapplied. You'll learn which parts add strength to object-oriented programming, and how to use certain features to integrate your application with databases. Written by a longtime member of the PHP community, PHP: The Good Parts is ideal for new PHP programmers, as well as web developers switching from other languages. Become familiar w

  2. Spare-part surgery.

    Science.gov (United States)

    Peng, Yeong Pin; Lahiri, Amitabha

    2013-11-01

    The authors discuss the use of scavenged tissue for reconstruction of an injured limb, also referred to as "spare-part surgery." It forms an important part of overall reconstructive strategy. Though some principles can be laid down, there is no "textbook" method for the surgeon to follow. Successful application of this strategy requires understanding of the concept, accurate judgment, and the ability to plan "on-the-spot," as well as knowledge and skill to improvise composite flaps from nonsalvageable parts. Requirements for limb reconstruction vary from simple solutions such as tissue coverage, which include skin grafts or flaps to more complex planning as in functional reconstruction of the hand, where the functional importance of individual digits as well as the overall prehensile function of the hand needs to be addressed right from the time of primary surgery. The incorporation of the concept of spare-part surgery allows the surgeon to carry out primary reconstruction of the limb without resorting to harvest tissue from other regions of the body.

  3. Basic Electricity. Part 2.

    Science.gov (United States)

    Kilmer, Donald C.

    This guide, the second (part 2) in a set of four guides, is designed for the student interested in a vocation in electrical work, and includes two units: Unit IV--Electrical Theory, covering thirteen lessons (matter, the atom, electrical charges in the atom, rules of electric charges, electricity, atoms in an electrical conductor, electrical…

  4. Anaemia (part 2)

    African Journals Online (AJOL)

    SA immigration laws. This led to an influx of visitors for business, leisure and employment purposes from various parts of the world. Consequently, healthcare workers are now exposed to inherited haemolytic conditions previously not highly prevalent in SA. Physiological states of anaemia,. e.g. pregnancy, are not included ...

  5. Pallet part grading trainer

    Science.gov (United States)

    Deborah F. Cook; Philip A. Araman; Matthew F. Winn

    2000-01-01

    A computerized pallet grading training system was developed to facilitate the production of higher quality pallets. Higher quality pallets would be more durable and could be re-used many times, resulting in long-term savings. Schmoldt et al. (1993) evaluated the economic impact of grading and sorting pallet parts. They determined that higher quality pallets produced by...

  6. Pieces and Parts

    Science.gov (United States)

    Miller, Deborah A.; Ellis, Edith B.

    2006-01-01

    Although critical to understanding human sexuality and reproductive physiology, the male and female reproductive anatomy is often minimally covered by teachers. For teachers and students alike, it is often an embarrassing topic to discuss. This activity allows students and teachers to identify the parts of both reproductive systems with little…

  7. Radiopharmaceuticals as probes to characterize tumour tissue

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Israt S.; Arshad, Mubarik A.; Nguyen, Quang-De; Aboagye, Eric O. [Imperial College London, Comprehensive Cancer Imaging Centre, London (United Kingdom)

    2015-04-01

    Tumour cells exhibit several properties that allow them to grow and divide. A number of these properties are detectable by nuclear imaging methods. We discuss crucial tumour properties that can be described by current radioprobe technologies, further discuss areas of emerging radioprobe development, and finally articulate need areas that our field should aspire to develop. The review focuses largely on positron emission tomography and draws upon the seminal 'Hallmarks of Cancer' review article by Hanahan and Weinberg in 2011 placing into context the present and future roles of radiotracer imaging in characterizing tumours. (orig.)

  8. Dendrimers as Innovative Radiopharmaceuticals in Cancer Radionanotherapy.

    Science.gov (United States)

    Liko, Flonja; Hindré, François; Fernandez-Megia, Eduardo

    2016-10-10

    Radiotherapy is one of the most commonly used cancer treatments, with an estimate of 40% success that could be improved further if more efficient targeting and retention of radiation at the tumor site were achieved. This review focuses on the use of dendrimers in radionanotherapy, an emerging technology aimed to improve the efficiency of radiotherapy by implementing nanovectorization, an already established praxis in drug delivery and diagnosis. The labeling of dendrimers with radionuclides also aims to reduce the dose of radiolabeled materials and, hence, their toxicity and tumor resistance. Examples of radiolabeled dendrimers with alpha, beta, and Auger electron emitters are commented, along with the use of dendrimers in boron neutron capture therapy (BNCT). The conjugation of radiolabeled dendrimers to monoclonal antibodies for a more efficient targeting and the application of dendrimers in gene delivery radiotherapy are also covered.

  9. Dual radiopharmaceutical imaging in congenital asplenia syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Rao, B.K.; Shore, R.M.; Lieberman, L.M.; Polcyn, R.E.

    1982-12-01

    Asplenia was suspected in one patient with combined immunodeficiency syndrome and 5 with congenital cardiac anomalies who had Howell-Jolly bodies on peripheral blood smears. /sup 99m/Tc-sulfur colloid scans were equivocal for absence of the spleen. When they were compared with the /sup 99m/Tc-PIPIDA hepatobiliary images, a discrepancy in organ morphology between the two scans indicated that the spleen was present, whereas similarity of the two images suggested asplenia. This procedure was useful in establishing asplenia in 4 patients and confirming the presence of a rudimentary or ectopic spleen in 2 others. Unequivocal demonstration of the spleen on the sulfur colloid scans makes the hepatobiliary study unnecessary, while unequivocal demonstration of a normal-appearing liver without splenic activity may warrant a tagged red-cell study for a more complete evaluation.

  10. Dual radiopharmaceutical imaging in congenital asplenia syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Rao, B.K. (Univ. Hospital, Cleveland, OH); Shore, R.M.; Lieberman, L.M.; Polcyn, R.E.

    1982-12-01

    Asplenia was suspected in one patient with combined immunodeficiency syndrome and 5 with congenital cardiac anomalies who had Howell-Jolly bodies on peripheral blood smears. /sup 99//sup m/Tc-sulfur colloid scans were equivocal for absence of the spleen. When they were compared with the /sup 99//sup m/Tc-PIPIDA hepatobiliary images, a discrepancy in organ morphology between the two scans indicated that the spleen was present, whereas similarity of the two images suggested asplenia. This procedure was useful in establishing asplenia in 4 patients and confirming the presence of a rudimentary or ectopic spleen in 2 others. Unequivocal demonstration of the spleen on the sulfur colloid scans makes the hepatobiliary study unnecessary, while unequivocal demonstration of abnormal-appearing liver without splenic activity may warrant a tagged red-cell study for a more complete evaluation.

  11. Recent developments in cyclotron-produced radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, A.M.

    1981-01-01

    The major areas of interest over the past two years are briefly reviewed. These include: (1) tracers for in vivo measurements of blood flow; (2) tracers for in vivo measurements of regional metabolism; (3) tracers for the measurement of receptor sensitivities; and (4) radioisotope generator systems. (ACR)

  12. Computational system for activity calculation of radiopharmaceuticals

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... 3- “Tempo de síntese”, “Controle de Qualidade” and. “Embalagen e Expedição”- this field are related to the estimates times spent in the respectively process of synthesis, quality control and packaging and shipment. Santos-Oliveira and Benevides 4983. After full entry of all these fields, the “Calcular” bottom.

  13. Standardization of Administered Activities in Pediatric Nuclear Medicine: A Report of the First Nuclear Medicine Global Initiative Project, Part 2-Current Standards and the Path Toward Global Standardization.

    Science.gov (United States)

    Fahey, Frederic H; Bom, Henry Hee-Seung; Chiti, Arturo; Choi, Yun Young; Huang, Gang; Lassmann, Michael; Laurin, Norman; Mut, Fernando; Nuñez-Miller, Rodolfo; O'Keeffe, Darin; Pradhan, Prasanta; Scott, Andrew M; Song, Shaoli; Soni, Nischal; Uchiyama, Mayuki; Vargas, Luis

    2016-07-01

    The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of 13 international organizations with direct involvement in nuclear medicine. The underlying objectives of the NMGI are to promote human health by advancing the field of nuclear medicine and molecular imaging, encourage global collaboration in education, and harmonize procedure guidelines and other policies that ultimately lead to improvements in quality and safety in the field throughout the world. For its first project, the NMGI decided to consider the issues involved in the standardization of administered activities in pediatric nuclear medicine. It was decided to divide the final report of this project into 2 parts. Part 1 was published in this journal in the spring of 2015. This article presents part 2 of the final report. It discusses current standards for administered activities in children and adolescents that have been developed by various professional organizations. It also presents an evaluation of the current practice of pediatric nuclear medicine specifically with regard to administered activities as determined by an international survey of 313 nuclear medicine clinics and centers from 29 countries. Lastly, it provides recommendations for a path toward global standardization of the administration of radiopharmaceuticals in children. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. Biodistribution dosimetric study of radiopharmaceutical {sup 99mT}c Ixolaris in mice for melanoma diagnosis by molecular image and translational model for human beings; Estudo dosimetrico da biodistribuicao do radiofarmaco Ixolaris-{sup 99m}Tc em camundongos para diagnostico de melanoma atraves de imagem molecular e modelo translacional para humanos

    Energy Technology Data Exchange (ETDEWEB)

    Soriano, Sarah Canuto Silva

    2015-07-01

    The labeling of Ixolaris with {sup 99m}Tc was developed by Barboza et.al. (2013) aiming its use primarily in glioblastoma and after in melanoma diagnosis, a less common but very aggressive cancer and with high mortality rate. Preliminary tests on animals have proven its effectiveness of labeling but a dosimetric study to human clinical trials should be performed. This study aimed to: (1) determine the biokinetic model for the radiotracer {sup 99m}Tc-Ixolaris in mice by imaging dosimetry method; and (2) estimate the absorbed and effective dose resulting from the use of a new radiopharmaceutical for melanoma and metastases diagnosis in human beings, since a dosimetric study of new radiopharmaceuticals in animals is necessary to test them subsequently in humans and apply for registration in ANVISA. According to SPECT images, was found a latency period of 15 to 21 days for the development of lung metastasis in mice. Three C57BL6 mice, one control animal, and two animals with induced cell line B16-F10 murine melanoma were tested. The {sup 99m}Tc-Ixolaris radiopharmaceutical was administered intravenously in a caudal vein, and SPECT images were acquired 0.5 h, 1.5 h, 2.5 h, 3.5 h and 24 h post-administration for analysis and biodistribution quantification. The biokinetic model was determined and thus, obtained cumulative activity in order to estimate the absorbed dose in each organ. The mass and metabolic differences between mice and humans were considered and used to extrapolate the data acquired at different scales. Based on dose factors provided by the software MIRDOSE and Olinda (S factor), absorbed doses in irradiated target organs were calculated for the source organs, and finally the effective dose was estimated. The results indicate that for diagnostic exams conducted in human melanoma patients by administering approximately 25.7 MBq the estimated effective dose was 4.3 mSv. Comparing with effective doses obtained in other diagnostic techniques with {sup 99m

  15. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical; Estudo do mecanismo de acao da crotoxina em tumores mamarios e avaliacao do seu potenctial radiofarmaceutico

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina Bicalho

    2010-07-01

    /cell high affinity binding sites; moreover, the radiolabeled polypeptide interaction showed low specificity toward to MCF-7 (37%). EGF reduced 20% of {sup 125}I-Crotoxin specific binding, so specific binding sites of Crotoxin on Ehrlich tumor cells partially overlap to EGFR. Crotoxin biodistribution studies showed significant uptake in the tumor paw (tumor/skeletal muscle ratio= 18.55), three hours after administration. SPECT imaging also showed tumor uptake confirming in vivo interaction with Ehrlich tumor cells. Crotoxin had an antitumoral effect on Ehrlich tumor cells and this action is due, at least partially, to the specific interaction with low and high affinity binding sites. Low affinity binding sites correlate EGFR and high affinity binding sites still need identification. These results confirm Crotoxin as a template for radiopharmaceutical design for cancer diagnosis and as a tool for cancer studies, increasing its biotechnological potential. (author)

  16. Endocrine system: part 1.

    Science.gov (United States)

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  17. R806 (part 1)

    CERN Multimedia

    CERN PhotoLab

    1976-01-01

    R806 was designed by the BNL-CERN-Syracuse-Yale Collaboration (Bill Willis spokesman) to study large transverse momentum phenomena, and installed in intersection 8 of the ISR. The main detectors were Lithium foil transition radiation detectors to identify electrons and liquid argon calorimeters to measure the energy of the electrons and photons (among the first such calorimeters to be used in an experiment). In part 1 there were two modules, top and bottom of the horizontal beam pipe; the black vertical pipe contains the cryogenics (LN2 and Lar) and is connected to the two modules with the horizontal piping.

  18. Java The Good Parts

    CERN Document Server

    Waldo, Jim

    2010-01-01

    What if you could condense Java down to its very best features and build better applications with that simpler version? In this book, veteran Sun Labs engineer Jim Waldo reveals which parts of Java are most useful, and why those features make Java among the best programming languages available. Every language eventually builds up crud, Java included. The core language has become increasingly large and complex, and the libraries associated with it have grown even more. Learn how to take advantage of Java's best features by working with an example application throughout the book. You may not l

  19. Mapping sequences by parts

    Directory of Open Access Journals (Sweden)

    Guziolowski Carito

    2007-09-01

    Full Text Available Abstract Background: We present the N-map method, a pairwise and asymmetrical approach which allows us to compare sequences by taking into account evolutionary events that produce shuffled, reversed or repeated elements. Basically, the optimal N-map of a sequence s over a sequence t is the best way of partitioning the first sequence into N parts and placing them, possibly complementary reversed, over the second sequence in order to maximize the sum of their gapless alignment scores. Results: We introduce an algorithm computing an optimal N-map with time complexity O (|s| × |t| × N using O (|s| × |t| × N memory space. Among all the numbers of parts taken in a reasonable range, we select the value N for which the optimal N-map has the most significant score. To evaluate this significance, we study the empirical distributions of the scores of optimal N-maps and show that they can be approximated by normal distributions with a reasonable accuracy. We test the functionality of the approach over random sequences on which we apply artificial evolutionary events. Practical Application: The method is illustrated with four case studies of pairs of sequences involving non-standard evolutionary events.

  20. Part Objects and Their Location

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann; Møller-Pedersen, Birger

    1992-01-01

    The notion of location of part objects is introduced, yielding a reference to the containing object. Combined with locally defined objects and classes (block structure), singularly defined part objects, and references to part objects, it is a powerful language mechanism for defining objects...... with different aspects or roles. The use of part objects for inheritance of code is also explored....

  1. Rickets: Part I.

    Science.gov (United States)

    Shore, Richard M; Chesney, Russell W

    2013-01-01

    Rickets is characterized by impaired mineralization and ossification of the growth plates of growing children caused by a variety of disorders, the most frequent of which is nutritional deficiency of vitamin D. Despite ample knowledge of its etiology and the availability of cost-effective methods of preventing it, vitamin D deficiency rickets remains a significant problem in developing and developed countries. This two-part review covers the history, etiology, pathophysiology and clinical and radiographical findings of vitamin D deficiency rickets. Other less frequent causes of rickets and some of the disorders entering into the differential diagnoses of rickets are also considered. Controversial issues surrounding vitamin D deficiency include determination of what constitutes vitamin D sufficiency and the potential relationship between low levels of vitamin D metabolites in many individuals and unexplained fractures in infants.

  2. Using UNIX, Part 2.

    Science.gov (United States)

    Mann, J

    2001-01-01

    We talked about using 3 UNIX commands. In UNIX, there are many other options for using them. But for the most part, if you can use them like I have shown, you will be able to do everything you need. If you can learn these few points well, I think you will be better off than if I give you 50 options and leave you totally confused about when to do what. On some UNIX systems, an electronic version of the UNIX manual is on the system. This gives a lot more information about each command. However, it is a bit difficult to understand. If you want more information about any command, you can type man COMMAND, e.g., man ls. This will give you more ways to use the ls command. And remember, the command pwd tells what directory you are in, cd/directory changes to another directory, ls lists the contents of the directory you are in, ls more displays the directory contents 1 page at a time (the space bar gives you the next page), ls-al gives a detailed listing of the contents of the directory you are in, ls-al more displays them 1 page at a time (the space bar gives you the next page).

  3. Cardiovascular Health, Part 1

    Science.gov (United States)

    Gupta, Sanjaya; Baman, Timir; Day, Sharlene M.

    2009-01-01

    Context: Identification of potentially fatal cardiac conditions in otherwise healthy athletes presents a major challenge to the sports medicine community. The requirements for preparticipation screening vary among countries and even from state to state within the United States. The mandated use of an electrocardiogram as a screening implement has provoked international controversy. Evidence acquisition: Part 1 of this review highlights the current guidelines and controversies surrounding cardiovascular screening, with a focus on the diagnostic challenges associated with identifying athletes with inheritable cardiomyopathies. Data sources were limited to peer-reviewed publications from 1984 to the present. Results: Preparticipation screening should include at least a history and a physical examination for all athletes, whereas use of an electrocardiogram is still controversial. Diagnosis of inherited cardiomyopathies presents unique challenges, particularly in hypertrophic cardiomyopathy, where many features can mimic those found in the “athlete’s heart.” Conclusions: Recognizing cardiac conditions in athletes that can predispose them to sudden cardiac death or other adverse outcomes is of vital importance, as is the appropriate exclusion of these athletes from competition. Further studies are needed to determine the most efficient and cost-effective means of screening and to increase the sensitivity and specificity of diagnostic testing for inheritable cardiovascular diseases. PMID:23015913

  4. No Spare Parts: Sharing Part Detectors for Image Categorization

    NARCIS (Netherlands)

    Mettes, P.; van Gemert, J.C.; Snoek, C.G.M.

    2016-01-01

    This work aims for image categorization by learning a representation of discriminative parts. Different from most existing part-based methods, we argue that parts are naturally shared between image categories and should be modeled as such. We motivate our approach with a quantitative and qualitative

  5. The subthalamic nucleus, Part I

    NARCIS (Netherlands)

    Marani, Enrico; Heida, Tjitske; Lakke, Egbert A.J.F.; Usunoff, Kamen G.

    2008-01-01

    Part I. Development, cytology, topography and connections. This monograph on the subthalamic nucleus accentuates in Part I the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology

  6. Medicare Utilization for Part B

    Data.gov (United States)

    U.S. Department of Health & Human Services — This link takes you to the Medicare utilization statistics for Part B (Supplementary Medical Insurance SMI) which includes the Medicare Part B Physician and Supplier...

  7. Exploring Water Pollution. Part II

    Science.gov (United States)

    Rillo, Thomas J.

    1975-01-01

    This is part two of a three part article related to the science activity of exploring environmental problems. Part one dealt with background information for the classroom teacher. Presented here is a suggested lesson plan on water pollution. Objectives, important concepts and instructional procedures are suggested. (EB)

  8. Genotoxic and cytotoxic damage by the therapeutic radiopharmaceutical [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP as in vivo generator system; Dano genotoxico y citotoxico por el radiofarmaco terpeutico [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP como sistema de generador in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Pedraza L, M.; Piedras R, J. [Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran. Vasco. de Quiroga 15, 14000 Mexico D.F. (Mexico); Ferro F, G.; Morales R, P. [ININ, Km. 36.5 Carretera Mexico-Toluca, Ocoyoacac, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santaelena, Mexico D.F. (Mexico); Hernandez O, O. [Escuela Superior de Fisica y Matematicas, IPN, Mexico D.F. (Mexico)

    2005-07-01

    In patients with leukemias and multiple myeloma, the cure can be obtained to inclination of a bone marrow transplant (m.o.), for that which one is used a combination of external radiotherapy and chemotherapy with the consequent toxicity to healthy organs. The complex [{sup 166}Dy]Dy/{sup 166}Ho-ethylenediaminetetramethylenephosphonate ([{sup 166}Dy]Dy/{sup 166}Ho-EDTMP) it forms a generator system in vivo stable with bony selective likeness in mice therefore, this it could work as a therapeutic radiopharmaceutical for bone marrow ablation. The objective of this original work was to determine the genotoxic and cytotoxic damage produced by the [{sup 166}Dy]Dy/{sup 166}Ho-EDTMP like a generator system in vivo by means of the reticulocytes reduction (RET) and micronucleus elevation in reticulocytes (RET-MN) in peripheral blood and to evaluate its myeloablative potential for histopathologic studies. It was irradiated {sup 166}Dy{sub 2}O{sub 3} enriched and it was add in form {sup 166}DyCI{sub 3} to the EDTMP in a softening media of phosphates (pH 8), the optimal molar relationship {sup 166}Dy: EDTMP was 1.7:1 and the radiochemical purity was evaluated by ITLC. The Dy:EDTMP complexes, non radioactive, its were prepared in the same way with non irradiated dysprosium oxide. A group of BALB/c mice was injected intraperitoneally with the radiopharmaceutical and two groups of control mice were injected with the non radioactive complex and with sodium chloride 0.9% respectively. Before injecting each one of the solutions it was take a basal sample of peripheral blood of the mouse tail and each 48 h post-injection during 12 d. The animals were sacrificed to obtain the organs of interest and to determine the radioactivity in each one. The femur was used for the histopathologic studies. The quantification of the frequency of RET and RET-MN was carried out by flow cytometry of the sanguine samples and the Monte Carlo code MCNP4B for the dosimetry calculations was used. The

  9. Evaluation of the cell death mechanisms activated by the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy; Evaluacion de los mecanismos de muerte celular activados por el radiofarmaco {sup 177}Lu-DOTA-anti-CD20 en un intervalo de dosis de 1 a 5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G., E-mail: erica.azorin@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2016-10-15

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation

  10. Evaluation of cell death mechanisms activated by the administration of the theranostics radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1-5 Gy; Evaluacion de los mecanismos de muerte celular activados por la administracion del radiofarmaco teranostico {sup 177}Lu-DOTA-anti-CD20 en un rango de dosis de 1-5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Martinez V, B. E.

    2016-07-01

    Radio-immunotherapy with anti-CD20 antibodies significantly increases the rate of remission in patients with CD20 over expressing B-cell lymphomas. Radio-labeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. Anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum soft tissue reach of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of synergistic activation of anti-CD20 and radionuclide have not been studied. In this work we evaluated by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-anti-CD20 from non-Hod king lymphoma cells (Raji). The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation activation of repair mechanisms and increased radio-sensitivity) causes acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation, which leads to cell arrest

  11. Synthesis and evaluation in vitro in cancer cells AR42J of the radiopharmaceutical {sup 99m}Tc-Tyr{sup 3}-Octreotide-dendrimer similar of somatostatin; Sintesis y evaluacion in vitro en celulas de cancer AR42J del radiofarmaco {sup 99m}Tc-Tyr{sup 3}-Octreotido-dendrimero analogo de la somatostatina

    Energy Technology Data Exchange (ETDEWEB)

    Orocio R, E.

    2013-07-01

    The objective of this project was preparing a multimeric system through the conjugation of several molecules of the peptide Tyr{sup 3}-Octreotide to a dendrimer molecule based on Poly-amidoamine (PAMAM), as well as radiolabeled with {sup 99m}Tc and evaluating its behavior like new radiopharmaceutical similar of somatostatin. The dendrimer PAMAM generation 3.5 that possesses terminal groups of sodium carboxylate, was functionalized to peptide Tyr{sup 3}-Octreotide through a reaction of peptide coupling with HATU (hexafluorophosphate (V) of 1-oxide-3-(bis(dimethylamino)methylene)-3H-[1,2,3]triazole[4,5-b]pyridine) as activating agent of carboxylate groups using the Size Exclusion Chromatography (Sec) as purification method. The product was characterized by Ultraviolet visible spectrophotometry, Mid-infrared and Far-infrared, Elemental analysis, Energy dispersive X-ray spectroscopy, Scanning electron microscopy, Thermogravimetry and Differential scanning calorimetry. The radiolabeled with {sup 99m}Tc was carried out using a direct method that involves the reduction of the anion TcO{sub 4}{sup -} with stannous chloride, so that the dendrimer is capable of coordinating to the technetium forming a chelate compound. The radiochemical purity of the radiolabeled compound was determined by thin layer chromatography using a sodium chloride solution to 20% (m/v) as mobile phase and was verified by molecular exclusion chromatography. The radiolabeled compound was possible to obtain it with a radiochemical purity superior to 90%. Also, the specific and not specific union was evaluated of the synthesized compound in mouse pancreas cancer cells AR42J, positive to somatostatin receptors, showing specific recognition for this receptors type with high cellular internalization. The biodistribution studies were carried out in BALB/c mice at different post injection times and in nude mice with induced tumors AR42J. The results showed that the {sup 99m}Tc-PAMAM-Tyr{sup 3}-Octreotide is

  12. Development of a specific radiopharmaceutical based on gold nanoparticles functionalized with HYNIC-peptide/mannose for the sentinel lymph node detection in breast cancer; Desarrollo de un radiofarmaco especifico basado en nanoparticulas de oro funcionalizadas con HYNIC-peptido/manosa para la deteccion de ganglio centinela en cancer de mama

    Energy Technology Data Exchange (ETDEWEB)

    Ocampo G, B. E.

    2012-07-01

    The aim of this research was to prepare a multifunctional system of {sup 99m}Tc-labelled gold nanoparticles conjugated to HYNIC-G GC/mannose and to evaluate its biological behaviour as a potential radiopharmaceutical for sentinel lymph node detection. Hydrazino nicotinyl-Gly-Gly-Cys-NH{sub 2} (HYNIC-G GC) peptide and a thiol-triazole-mannose derivative were synthesized, characterized and conjugated to gold nanoparticles (Au-Np, 20 nm) to prepare a multifunctional system of HYNIC-G GC-Au-Np-mannose by means of spontaneous reaction of the thiol (Cys) present in HYNIC-G GC sequence and in the thiol-mannose derivative. The nano conjugate was characterized by transmission electron microscopy (Tem), IR, UV-Vis, Raman, Fluorescence and X-ray photoelectron spectroscopy (XP S). {sup 99m}Tc labelling was carried out using EDDA/tricine as co ligands and SnCl{sub 2} as reducing agent with further size-exclusion chromatography purification. Radiochemical purity was determined by size-exclusion HPLC and I TLC-Sg analyses. In vitro binding studies were carried out in rat liver homogenized tissue (mannose-receptor positive tissue). Biodistribution studies were accomplished in Wistar rats and images obtained using a micro-SPECT/CT system. Tem and the spectroscopic techniques demonstrated that Au-Np were functionalized with HYNIC-G GC and thiol-mannose through interactions with thiol groups of cysteine. Radio-chromatograms showed radiochemical purity higher than 95%. {sup 99m}Tc-EDDA/HYNIC-G GC-Au-Np-mannose ({sup 99m}Tc-Au-Np-mannose) showed specific recognition for mannose receptors in rat liver tissue. After subcutaneous administration of {sup 99m}Tc-Au-Np-mannose in rats (foot pad), radioactivity levels in the popliteal and inguinal lymph nodes revealed that 99% of the activity was extracted by the first lymph node (popliteal extraction). Biodistribution studies and in vivo micro-SPECT/CT images in Wistar rats showed an evident lymph node uptake (11.58 {+-} 1.98% Id at 1 h

  13. Staircase and Fractional Part Functions

    Science.gov (United States)

    Amram, Meirav; Dagan, Miriam; Ioshpe, Michael; Satianov, Pavel

    2016-01-01

    The staircase and fractional part functions are basic examples of real functions. They can be applied in several parts of mathematics, such as analysis, number theory, formulas for primes, and so on; in computer programming, the floor and ceiling functions are provided by a significant number of programming languages--they have some basic uses in…

  14. Designing screened enclosures: Part II.

    Science.gov (United States)

    Bearpark, J

    2006-03-01

    Techniques to achieve cost-effective emissions and immunity screening solutions that meet electromagnetic compatibility requirements were provided in Part I of this article, which covered design options for seams and gaskets. Part II continues with a discussion of materials compatibility, corrosion and apertures.

  15. The MAJORANA Parts Tracking Database

    Science.gov (United States)

    Abgrall, N.; Aguayo, E.; Avignone, F. T.; Barabash, A. S.; Bertrand, F. E.; Brudanin, V.; Busch, M.; Byram, D.; Caldwell, A. S.; Chan, Y.-D.; Christofferson, C. D.; Combs, D. C.; Cuesta, C.; Detwiler, J. A.; Doe, P. J.; Efremenko, Yu.; Egorov, V.; Ejiri, H.; Elliott, S. R.; Esterline, J.; Fast, J. E.; Finnerty, P.; Fraenkle, F. M.; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guiseppe, V. E.; Gusev, K.; Hallin, A. L.; Hazama, R.; Hegai, A.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Keeter, K. J.; Kidd, M. F.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J. Diaz; Leviner, L. E.; Loach, J. C.; MacMullin, J.; Martin, R. D.; Meijer, S. J.; Mertens, S.; Miller, M. L.; Mizouni, L.; Nomachi, M.; Orrell, J. L.; O`Shaughnessy, C.; Overman, N. R.; Petersburg, R.; Phillips, D. G.; Poon, A. W. P.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Shanks, B.; Shima, T.; Shirchenko, M.; Snavely, K. J.; Snyder, N.; Soin, A.; Suriano, A. M.; Tedeschi, D.; Thompson, J.; Timkin, V.; Tornow, W.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Young, A. R.; Yu, C.-H.; Yumatov, V.; Zhitnikov, I.

    2015-04-01

    The MAJORANA DEMONSTRATOR is an ultra-low background physics experiment searching for the neutrinoless double beta decay of 76Ge. The MAJORANA Parts Tracking Database is used to record the history of components used in the construction of the DEMONSTRATOR. The tracking implementation takes a novel approach based on the schema-free database technology CouchDB. Transportation, storage, and processes undergone by parts such as machining or cleaning are linked to part records. Tracking parts provide a great logistics benefit and an important quality assurance reference during construction. In addition, the location history of parts provides an estimate of their exposure to cosmic radiation. A web application for data entry and a radiation exposure calculator have been developed as tools for achieving the extreme radio-purity required for this rare decay search.

  16. The Majorana Parts Tracking Database

    Energy Technology Data Exchange (ETDEWEB)

    Abgrall, N.; Aguayo, E.; Avignone, F. T.; Barabash, A. S.; Bertrand, F. E.; Brudanin, V.; Busch, M.; Byram, D.; Caldwell, A. S.; Chan, Y-D.; Christofferson, C. D.; Combs, D. C.; Cuesta, C.; Detwiler, J. A.; Doe, P. J.; Efremenko, Yu.; Egorov, V.; Ejiri, H.; Elliott, S. R.; Esterline, J.; Fast, J. E.; Finnerty, P.; Fraenkle, F. M.; Galindo-Uribarri, A.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guiseppe, V. E.; Gusev, K.; Hallin, A. L.; Hazama, R.; Hegai, A.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Keeter, K. J.; Kidd, M. F.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J. Diaz; Leviner, L. E.; Loach, J. C.; MacMullin, J.; Martin, R. D.; Meijer, S. J.; Mertens, S.; Miller, M. L.; Mizouni, L.; Nomachi, M.; Orrell, J. L.; O׳Shaughnessy, C.; Overman, N. R.; Petersburg, R.; Phillips, D. G.; Poon, A. W. P.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Shanks, B.; Shima, T.; Shirchenko, M.; Snavely, K. J.; Snyder, N.; Soin, A.; Suriano, A. M.; Tedeschi, D.; Thompson, J.; Timkin, V.; Tornow, W.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Young, A. R.; Yu, C. -H.; Yumatov, V.; Zhitnikov, I.

    2015-04-01

    The MAJORANA DEMONSTRATOR is an ultra-low background physics experiment searching for the neutrinoless double beta decay of 76Ge. The MAJORANA Parts Tracking Database is used to record the history of components used in the construction of the DEMONSTRATOR. Transportation, storage, and processes undergone by parts such as machining or cleaning are linked to part records. Tracking parts provides a great logistics benefit and an important quality assurance reference during construction. In addition, the location history of parts provides an estimate of their exposure to cosmic radiation. A web application for data entry and a radiation exposure calculator have been developed as tools for achieving the extreme radiopurity required for this rare decay search.

  17. Parts hindab oma valitsust "kolmega" / Juhan Parts ; interv. Toomas Sildam

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2005-01-01

    Peaminister Juhan Parts vastab küsimustele, mis puudutavad uue valitsuskoalitsiooni moodustamist. Peaminister peab oluliseks, et uus valitsus tekiks kiiresti, ning on nõus ise uue valitsuse kokku panema

  18. Otvetshajet Juhan Parts, premjer-ministr / Juhan Parts

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2005-01-01

    Peaminister Juhan Parts selgitab Res Publica ja valitsuse korruptsioonivastast poliitikat ning loodab, et justiitsminister Ken-Marti Vaheri pakutud strateegia võitluses korruptsiooniga ei saa koalitsiooni lagunemise põhjuseks

  19. Juhan Parts lubab investeerida teedesse / Juhan Parts ; interv. Tanel Raig

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2007-01-01

    Ilmunud ka: Delovõje Vedomosti 17. okt. lk. 13. Majandusminister Juhan Parts arutleb lahendamist vajavate küsimuste ja prioriteetsete investeeringute üle transpordisektoris. Lisa: Juhan Partsi kuus kuud ministrina

  20. Advanced modern algebra part 2

    CERN Document Server

    Rotman, Joseph J

    2017-01-01

    This book is the second part of the new edition of Advanced Modern Algebra (the first part published as Graduate Studies in Mathematics, Volume 165). Compared to the previous edition, the material has been significantly reorganized and many sections have been rewritten. The book presents many topics mentioned in the first part in greater depth and in more detail. The five chapters of the book are devoted to group theory, representation theory, homological algebra, categories, and commutative algebra, respectively. The book can be used as a text for a second abstract algebra graduate course, as a source of additional material to a first abstract algebra graduate course, or for self-study.

  1. 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 sol