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Sample records for astatine radiopharmaceuticals part

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

    Science.gov (United States)

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

    2008-04-01

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

  2. Nitroimidazole radiopharmaceuticals in bioimaging: part I: synthesis and imaging applications.

    Science.gov (United States)

    Sharma, Rakesh

    2011-10-01

    The paper is review on synthesis of nitroimidazole radiosensitizers useful in imaging of tumor cells. Nitroimidazole compounds are radiolabeled probes for specific use in imaging such as 18F for positron emission tomography; 99mTc for single photon emission computed tomography; 123I, or 131I for computer assisted tomography and 19F for magnetic resonance imaging. In synthesis of radiopharmaceutical compounds, parent nitroimidazole is modified to thiopyranosyl nucleosides, neuraminic acid derivatives followed by nitro group deprotection-substitution and radiolabeling by specific isotopes. Commercial attempts have been made to radiolabel the nitroimidazole by [18F]fluorine, [131I or 123I]iodine, [99mTc]technicium and [64Cu]copper on modified side chain of nitroimidazole compounds to design multimodal and multifunctional imaging techniques to detect and monitor the tumor hypoxia by measuring distribution of radiatiolabel or radiation. Nitroimidazole initially showed poor diffusion and poor stability in tissues with neurotoxicity concern limited its use as radiosensitizer. In last decade, several nitroimidazole derivatives were developed as potent less toxic and highly stable radiopharmaceuticals with optimized radiolabel concentration with high detectability of tumor oxygen or hypoxia. Currently, nitroimidazole based radiopharmaceuticals have emerged as multimodal and multifunctional hypoxia reporters with antitumor, anti-ischemic, anti-inflammatory and tumor targeting properties. In conclusion, nitroimidazole based radiopharmaceuticals are a new generation hypoxia biosensors for localized theradiagnostic utility in clinical medicine.

  3. Medicinal Radiopharmaceutical Chemistry of Metal Radiopharmaceuticals

    Science.gov (United States)

    Saw, Maung Maung

    2012-06-01

    Metal complexes have been used as medicinal compounds. Metals have advantageous features over organic compounds. Significant applications of metal complexes are in the field of nuclear medicine. Radiopharmaceuticals are drugs containing radioisotopes used for diagnostic and therapeutic purposes. The generalized targeting strategy for molecular imaging probe consists of three essential parts: (i) reporter unit or payload, (ii) carrier, and (iii) targeting system. Medicinal radiopharmaceutical chemistry pays special consideration to radioisotopes, as a reporter unit for diagnostic application or as a payload for therapeutic application. Targeting is achieved by a few approaches but the most common is the bifunctional chelator approach. While designing a radiopharmaceutical, a range of issues needs to be considered including properties of metal radioisotopes, bifunctional chelators, linkers, and targeting molecules. Designing radiopharmaceuticals requires consideration of two key words: "compounds of biological interest" and "fit for intended use." The ultimate goal is the development of new diagnostic methods and treatment. Diagnostic metal radiopharmaceuticals are used for SPECT and PET applications. Technetium chemistry constitutes a major portion of SPECT and gallium chemistry constitutes a major portion of PET. Therapeutic radiopharmaceuticals can be constructed by using alpha-, beta minus-, or Auger electron-emitting radiometals. Special uses of medicinal radiopharmaceuticals include internal radiation therapy, brachytherapy, immunoPET, radioimmunotherapy, and peptide receptor radionuclide imaging and therapy.

  4. 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.

  5. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride.

    Science.gov (United States)

    Pandit-Taskar, Neeta; Larson, Steven M; Carrasquillo, Jorge A

    2014-02-01

    Metastatic disease to bone is commonly seen in the advanced stages of many cancers. The cardinal symptom, pain, is often the cause of significant morbidity and reduced quality of life. Treatment of bone pain includes nonsteroidal analgesics and opiates; however, long-term use of these drugs is commonly associated with significant side effects, and tolerance is common. External-beam radiation therapy is effective mainly in localized disease sites. Bone-targeting radiopharmaceuticals are beneficial in the management of patients with multiple metastatic lesions. This article focuses on the 3 most commonly used agents: the Food and Drug Administration-approved (89)Sr-chloride, (153)Sm-ethylenediaminetetramethylene phosphonic acid (EDTMP), and (223)Ra-dichloride. We will discuss the physical characteristics, clinical data, dosage, and administration of these agents, including optimal patient selection and toxicity associated with their use. These radioactive agents have proven efficacy in the treatment of painful osseous metastases from prostate cancer and breast cancer. Significant recent advances include use of these agents in combination with chemotherapy and the use of the α emitter (223)Ra-dichloride in prostate cancer, primarily to improve survival and skeletal related events. The review is presented in 2 parts. The first will discuss the characteristics and clinical use of (223)Ra-dichloride, and the second will discuss the β emitters (89)Sr and (153)Sm-EDTMP.

  6. Astatine-211: production and availability.

    Science.gov (United States)

    Zalutsky, Michael R; Pruszynski, Marek

    2011-07-01

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

  7. 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

  8. 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.

  9. [Nuclear medicine and radiopharmaceuticals].

    Science.gov (United States)

    Sopena Novales, P; Plancha Mansanet, M C; Martinez Carsi, C; Sopena Monforte, R

    2014-06-01

    Nuclear Medicine is a medical specialty that allows modern diagnostics and treatments using radiopharmaceuticals original radiotracers (drugs linked to a radioactive isotope). In Europe, radiopharmaceuticals are considered a special group of drugs and thus their preparation and use are regulated by a set of policies that have been adopted by individual member countries. The radiopharmaceuticals used in diagnostic examinations are administered in very small doses. So, in general, they have no pharmacological action, side effects or serious adverse reactions. The biggest problem associated with their use are the alterations in their biodistribution that may cause diagnostic errors. Nuclear Medicine is growing considerably influenced by the appearance and development of new radiopharmaceuticals in both the diagnostic and therapeutic fields and primarily to the impact of new multimodality imaging techniques (SPECT-CT, PET-CT, PET-MRI, etc.). It's mandatory to know the limitations of these techniques, distribution and eventual physiological alterations of radiopharmaceuticals, contraindications and adverse reactions of radiological contrasts, and the possible interference of both.

  10. 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.

  11. 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)

  12. 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.

  13. Japanese consensus guidelines for pediatric nuclear medicine. Part 1: Pediatric radiopharmaceutical administered doses (JSNM pediatric dosage card). Part 2: Technical considerations for pediatric nuclear medicine imaging procedures.

    Science.gov (United States)

    Koizumi, Kiyoshi; Masaki, Hidekazu; Matsuda, Hiroshi; Uchiyama, Mayuki; Okuno, Mitsuo; Oguma, Eiji; Onuma, Hiroshi; Kanegawa, Kimio; Kanaya, Shinichi; Kamiyama, Hiroshi; Karasawa, Kensuke; Kitamura, Masayuki; Kida, Tetsuo; Kono, Tatsuo; Kondo, Chisato; Sasaki, Masayuki; Terada, Hitoshi; Nakanishi, Atsushi; Hashimoto, Teisuke; Hataya, Hiroshi; Hamano, Shin-ichiro; Hirono, Keishi; Fujita, Yukihiko; Hoshino, Ken; Yano, Masayuki; Watanabe, Seiichi

    2014-06-01

    The Japanese Society of Nuclear Medicine has recently published the consensus guidelines for pediatric nuclear medicine. This article is the English version of the guidelines. Part 1 proposes the dose optimization in pediatric nuclear medicine studies. Part 2 comprehensively discusses imaging techniques for the appropriate conduct of pediatric nuclear medicine procedures, considering the characteristics of imaging in children.

  14. 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)

  15. PET radiopharmaceuticals for neuroreceptor imaging

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Routine clinical PET radiopharmaceuticals for the noninvasive imaging of brain receptors, transporters,and enzymes are commonly labeled with positron emitting nuclides such as carbon-11 or fluorine-18. Certain minimal conditions need to be fulfilled for these PET ligands to be used as imaging agents in vivo. Some of these prerequisites are discussed and examples of the most useful clinical PET radiopharmaceuticals that have found application in the central nervous system are reviewed.

  16. Development of radiopharmaceuticals

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    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.

  17. 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.

  18. 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.

  19. 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.

  20. Bioinorganic Activity of Technetium Radiopharmaceuticals.

    Science.gov (United States)

    Pinkerton, Thomas C.; And Others

    1985-01-01

    Technetium radiopharmaceuticals are diagnostic imaging agents used in the field of nuclear medicine to visualize tissues, anatomical structures, and metabolic disorders. Bioavailability of technetium complexes, thyroid imaging, brain imaging, kidney imaging, imaging liver function, bone imaging, and heart imaging are the major areas discussed. (JN)

  1. Lymphoscintigraphy: radiopharmaceutical selection and methods

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, E.L. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))

    1990-01-01

    The range of radiopharmaceuticals available for lymphoscintigraphy including radiocolloids, radiolabeled macromolecules and monoclonal antibodies are briefly discussed. The techniques used for tumour staging in internal mammary lymphoscintigraphy, iliopelvic lymphoscintigraphy, peripheral lymphoscintigraphy, localization of 'at risk' lymph nodes and lymphedema are also reviewed. (UK).

  2. 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.

  3. 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.

  4. 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.

  5. 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)

  6. 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)

  7. Radiopharmaceutical chemistry for positron emission tomography

    NARCIS (Netherlands)

    Elsinga, PH

    2002-01-01

    Radiopharmaceutical chemistry includes the selection, preparation, and preclinical evaluation of radiolabeled compounds. This paper describes selection criteria for candidates for positron emission tomography (PET) investigations. Practical aspects of nucleophilic and electrophilic F-18-fluorination

  8. 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.

  9. (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.

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

    DEFF Research Database (Denmark)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom

    2015-01-01

    and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting......To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical...

  11. 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

  12. Applications of click chemistry in radiopharmaceutical development.

    Science.gov (United States)

    Walsh, Joseph C; Kolb, Hartmuth C

    2010-01-01

    Click chemistry, a concept that employs only practical and reliable transformations for compound synthesis, has made a significant impact in several areas of chemistry, including material sciences and drug discovery. The present article describes the use of click chemistry for the development of radiopharmaceuticals. Target templated in situ click chemistry was used for lead generation. The 1,2,3-triazole moiety was found to improve the pharmacokinetic properties of certain radiopharmaceuticals. The reliable Cu(I)-catalyzed click reaction was employed for radiolabeling of peptidic compounds without the need for protecting groups. In summary, the click chemistry approach for the discovery, optimization and labeling of new radiotracers, represents a very powerful tool for radiopharmaceutical development.

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

    NARCIS (Netherlands)

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

    2013-01-01

    The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of the minute quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical behaviou

  14. Radiopharmaceuticals for imaging chronic lymphocytic inflammation

    NARCIS (Netherlands)

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

    2007-01-01

    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 precli

  15. Radiopharmaceuticals in China. Current status and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Hong-Mei; Liu, Bo-Li [Beijing Normal Univ. (China). Key Laboratory of Radiopharmaceuticals

    2014-04-01

    The review provides an overview of the current status of radiopharmaceuticals in China for in vivo clinical use and also describes some important advances in the past three decades. Development of the diagnostic and therapeutic radiopharmaceuticals as well as basic research on radiopharmaceutical chemistry are being introduced. The radiotracers developed in China include: (1) Brain perfusion imaging agents and CNS radiotracers for β-amyloid plaques, σ{sub 1} receptors, and dopamine D{sub 2} or D{sub 4} receptors; (2) {sup 99m}Tc- and {sup 18}F-labeled myocardial perfusion imaging agents; (3) tumor imaging agents including integrin-targeting radiotracer, novel sentinel lymph node imaging agents, hypoxia imaging agents, {sup 99m}Tc-labeled glucose derivatives, σ{sub 2} receptor imaging agents, folate receptor imaging agents, and potential radiotracers for imaging of human telomerase reverse transcriptase expression; (4) Potential infection imaging agents; (5) Potential asialoglycoprotein receptor imaging agents; (6) Other imaging agents. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed. (orig.)

  16. 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.

  17. Detection of sentinel nodes with radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Kunihiko; Michigishi, Takatoshi; Kinuya, Seigo; Konishi, Shota; Nakajima, Kenichi; Tonami, Norihisa [Kanazawa Univ. (Japan). School of Medicine

    2000-10-01

    Sentinel lymph nodes have been found to be an indicator of lymph node metastasis in breast cancer. In Japan, the theory and concept of sentinel lymph nodes in breast cancer have begun to be applied to carcinomas of the digestive system. Based on clinical experience in the detection of sentinel lymph nodes with radiopharmaceuticals, differences and similarities between the radiopharmaceuticals, methods, and techniques used to detect sentinel lymph nodes have been assessed in relation to breast cancer and carcinomas of the digestive system (including carcinomas of the esophagus and large intestine). The greatest difference between the methods used for breast and digestive cancers is the site of administration of the radiopharmaceutical. In breast cancer, the radiopharmaceutical is administered into a superficial organ (i.e., the mammary gland), whereas in carcinomas of the digestive system, it is administered into a deep organ (i.e., digestive tract). Another obvious difference is in lymph flow, i.e., the flow of the mammary glands is subcutaneous whereas lymph flow in the digestive tract is submucosal. Two radionuclide diagnostic methods are available to detect sentinel lymph nodes: sentinel lymphoscintigraphy with a gamma camera and a method that involves the use of a gamma probe intraoperatively. Radiopharmaceuticals used to detect sentinel lymph nodes must be smoothly transferred from the site of administration into the lymph, and uptake by the sentinel lymph node must continue for a long time without excessive flowing to lower reaches. The optimal particle size remains a matter of controversy, and no radiopharmaceuticals appropriate for lymphoscintigraphy have ever been approved in Japan. The authors compared the pharmacokinetics of three different radiopharmaceuticals used for sentinel lymphoscintigraphy in breast cancer ({sup 99m}Tc-labeled albumin, {sup 99m}Tc-labeled tin colloid, and {sup 99m}Tc-labeled phytic acid) and founded that the detection rate was

  18. 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

  19. Application of a small molecule radiopharmaceutical concept to improve kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Dept. of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Recently, large molecules or nanoparticles are actively studied as radiopharmaceuticals. However, their kinetics is problematic because of a slow penetration through the capillaries and slow distribution to the target. To improve the kinetics, a two-step targeting method can be applied by using small molecules and very rapid copper-free click reaction. Although this method might have limitations such as internalization of the first targeted conjugate, it will provide high target-to-non-target ratio imaging of radiopharmaceuticals. The majority of radiopharmaceuticals belong to small molecules of which the molecular weight is less than 2000 Da, and the molecular size is smaller than 2 nm generally. The outstanding feature of the small molecule radiopharmaceuticals compared to large molecules is with their kinetics. Their distribution to target and clearance from non-target tissues are very rapid, which is the essential requirement of radiopharmaceuticals. In conclusion, the small molecule radiopharmaceuticals generally show excellent biodistribution properties; however, they show poor efficiency of radioisotope delivery. Large molecule or nanoparticle radiopharmaceuticals have advantages of multimodal and efficient delivery, but lower target-to-non-target ratio. Two-step targeting using a bio-orthogonal copper-free click reaction can be a solution of the problem of large molecule or nanoparticle radiopharmaceuticals. The majority of radiopharmaceuticals belong to small molecules of which the molecular weight is less than 2000 Da, and the molecular size is smaller than 2 nm generally. The outstanding feature of the small molecule radiopharmaceuticals compared to large molecules is with their kinetics. Their distribution to target and clearance from non-target tissues are very rapid, which is the essential requirement of radiopharmaceuticals.

  20. 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

  1. The Radiopharmaceuticals Production and Research Centre established by the Heavy Ion Laboratory of the University of Warsaw

    Directory of Open Access Journals (Sweden)

    Choiński J.

    2014-03-01

    Full Text Available The Radiopharmaceuticals Production and Research Centre was recently installed on the premises of the Heavy Ion Laboratory, University of Warsaw. Equipped with a medical PETtrace p/d cyclotron , radiochemistry synthesis and dispensing units and a modern quality control laboratory the Centre is intended to produce regularly for commercial purposes the classic PET radiopharmaceuticals ( such -as e.g. FDG- . Situated on the largest Warsaw scientific campus OCHOTA, an important part of the Centre’s activities will also be devoted to the production of known species for preclinical studies and research into innovative radiopharmaceuticals in collaboration with other scientific units of this Campus as well as with members of the Warsaw Consortium for PET Collaboration. Research into the accelerator production route of 99mTc will also begin shortly.

  2. Trends in radiopharmaceutical dispensing in a regional nuclear pharmacy

    Energy Technology Data Exchange (ETDEWEB)

    Basmadjian, G.P.; Johnston, J.; Barker, K.; Ice, R.D.

    1982-11-01

    Dispensing trends for radiopharmaceuticals at a regional nuclear pharmacy over a 51-month period were studied. dispensing records of a regional nuclear pharmacy were analyzed with a forecasting procedure that uses univariate time data to produce time trends and autoregressive models. The overall number of prescriptions increased from 3500 to 5500 per quarter. Radiopharmaceuticals used in nuclear cardiology studies increased from less than 0.1% to 17.5% of total prescriptions dispensed, while radiopharmaceuticals used for brain imaging showed a steady decline from 29% to 11% of total prescriptions dispensed. The demand for other radiopharmaceuticals increased in areas such as renal studies, bone studies, lung studies, liver-function studies, and /sup 67/Ga tumor-uptake studies, and declined slightly for static liver studies. Changes in dispensing trends for radiopharmaceuticals will continue as the practice of nuclear medicine concentrates more on functional studies and as newer imaging techniques become used for other purposes.

  3. 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.

  4. State of the art and perspectives in radiopharmaceutical field since ACOMEN 8. International Conference (Bordeaux May 11-13, 2005); Le radiopharmaceutique: situation et perspectives depuis la 8. conference internationale de l'ACOMEN (Bordeaux, 11-12-13 mai 2005)

    Energy Technology Data Exchange (ETDEWEB)

    Vuillez, J.P.; Desruet, M.D. [CHU de Grenoble, Pole d' Imagerie, Clinique de Medecine Nucleaire, 38 (France); Desruet, M.D. [CHU de Grenoble, Service de Radiopharmacie, Clinique de Medecine Nucleaire, 38 (France); Mundler, O. [CHU La Timone, Service de Medecine Nucleaire, 13 - Marseille (France); Karcher, G. [CHU de Nancy, Service de Medecine Nucleaire, 54 (France)

    2009-02-15

    Since previous ACOMEN conference in 2005 on radiopharmaceuticals, many improvements have been encountered: active research has allowed the development of numerous new tracers of interest, with a large part dedicated for PET; clinical applications of radiopharmaceuticals have resulted in patients care improvement, both for management and survival; therapeutic applications are now fully recognized, as internal targeted radiotherapy could be considered as efficient in several cancer diseases; and regulation, despite remaining difficulties, will certainly become more favourable for radiopharmaceuticals. Thus we could make sure that radiopharmaceuticals use will be even more established in the next years. (authors)

  5. 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.

  6. 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

  7. Production of bromine-75, a new radionuclide for marking radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Paans, A.M.J.; Wiegman, T.; Hoeve, W.; Vaalburg, W. (Rijksuniversiteit Groningen (Netherlands). Academisch Ziekenhuis)

    1982-01-01

    Bromine-75 is the most useful of all bromine isotopes for nuclear medicine. Its properties like half-life, nuclear reactions, production and chemical preparation, as well as the preparation of radiopharmaceuticals containing bromine-75 are presented.

  8. Options for shielding the hand during dispensing and administration of radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Whitby, M.; Martin, C. J.

    2002-07-01

    Hospital staff manipulating radiopharmaceuticals may receive significant radiation doses to their hands. A study of hand doses has been carried out in a large radionuclide dispensary and in nuclear medicine departments in the West of Scotland and the implications of different shielding options considered. Doses received for individual manipulation during many routine sessions have been measured with an electronic extremity dose monitor. Doses received from dispensing of radiopharmaceuticals in nuclear medicine were 4 mGy per 10 GBq handled, compared to 0.2 mGy per 10 GBq for radionuclide dispensary staff. There were a number of reasons for the large difference, with one of the most important being the speed with which the manipulations were performed. The actions performed in nuclear medicine consist of dispensing into a syringe and injection. Withdrawal of radiopharmaceuticals made up the higher dose component 5 to 500 {mu}Sv per procedure as a siring shield was not used for this part of the procedure. Doses received from individual injections for which syringe shields were used varied from 1.5 to 300 {mu}Sv depending on the degree of difficulty experienced during the injection. The study has shown the effectiveness of using local shielding in dose reduction. Tungsten vial shields limit the radiation dose and are useful for handling large activities during radiopharmaceutical preparation. Syringe shields substantially reduce doses for individual manipulations and should be used for procedures in which accurate reading of the syringe scale is not required. This includes higher dose manipulations in the radionuclide dispensary and injections in nuclear medicine. (Author)

  9. Preparation of radiopharmaceutical formulations; Fremstilling av radioaktive farmasoeytiske blandinger

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.; Garlich, J.R.; Frank, R.K.; McMillan, K

    1998-03-16

    Radiopharmaceutical formulations for complexes comprising at least one radionuclide complexed with a ligand, or its physiologically-acceptable salts thereof, especially {sup 153}samarium-ethylenediaminetetramethylenephosphonic acid, which optionally contains a divalent metal ion, e.g. calcium, and is frozen, thawed, and then administered by injection. Alternatively, the radiopharmaceutical formulations must contain the divalent metal and are frozen only if the time before administration is sufficiently long to cause concern for radiolysis of the ligand. 2 figs., 9 tabs.

  10. 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)

  11. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    Science.gov (United States)

    Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

    Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

  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. Technetium-99m radiopharmaceuticals for in vivo diagnostics

    Directory of Open Access Journals (Sweden)

    Đokić Divna Đ.

    2005-01-01

    Full Text Available Technetiiim-99m is an ideal radionuclide with optimum decay characteristics. It can be obtained in sterile, pyrogen-free and carrier-free condition, as sodium pertechnetate (Na99mTcO4, from 99Mo/99Tc generator. Because of its six-hour physical half-life and monochromatic 140 keV photons free of -radiation, administration of small amounts of 99mTc solution is possible, without a significant radiation damage to the patient. Technetium eluted from the 99Mo/99mTc generator is in the highest oxidation form (+7. It can be used for diagnostic purposes alone, but it is often used for labeling different organic and inorganic compounds. As it is unreactive, reduction with a chemical reductant, (+1, (+3 and (+5 oxidation are necessary before use. Nowadays almost 80% of radiopharmaceuticals are based on 99mTc. Radiopharmaceuticals. Radiopharmaceuticals are radionuclides or radioactive compounds used in diagnosis and therapy of human diseases. A pharmaceutical is chosen based on its localization in the organ, or its participation in its physiological function. Radiation emitted from a radionuclide is detected by a radiation detector. The ability to incorporate available radionuclides into tracer molecules has been the main goal in developing radiopharmaceuticals. As radionuclides with nuclear characteristics used as either diagnostic or therapeutic radiopharmaceuticals, are predominantly metals, they can be designed as metal essential, whereby biological distribution is determined by coordination compound, or metal tagged, in which case the properties of the carrier molecule (ligand system determine the biological distribution. This paper reviews the development of 99mTc-radiopharmaceuticals. .

  15. 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

  16. 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.

  17. Labeling radiopharmaceuticals with Se-75: using Se-75 selenious acid

    Energy Technology Data Exchange (ETDEWEB)

    Sadek, S.A.; Basmadjian, G.P.; Ice, R.D. (Oklahoma Univ., Oklahoma City (USA). Health Sciences Center)

    1982-08-01

    A cheap, easy method of introducing high specific activity Se-75 into radiopharmaceuticals is described. Se-75 selenious acid is reduced with NaBH/sub 4/ producing the nucleophile NaHSe. Using this method, a fatty acid, cholesterol, estrogen and phenethylamine are all labelled with Se-75.

  18. 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)

  19. European regulatory framework on the use and development of pharmaceuticals and radiopharmaceuticals for pediatrics.

    Science.gov (United States)

    Mensonides-Harsema, Marguérite; Otte, Andreas

    2011-01-01

    A survey in 2000 revealed that only about 30% of the prescriptions in the European pediatric population were on the basis of evidence-based medicine (EbM). Less for radiopharmaceuticals and principally for diagnostics, radiologists throughout Europe are referred to the pediatric guidelines of the European Association of Nuclear Medicine (EANM), as none of the frequently used tracers have been evaluated in clinical trials in the different pediatric subgroups. Following a resolution to address the lack of EbM in children, the European Commission published the Pediatric Regulation EC 1901/2006 and its amendment EC 1902/2006, effective from 2007. This regulation foresees the development of evidence-based medicine in the pediatric population. This is effected through a set of principles like the mandatory pediatric investigation plan (PIP) to be included with the market authorization application (MAA), and the pediatric use market authorization (PUMA) for off-patent pharmaceuticals, and to a very small part radiopharmaceuticals with funding possibilities for pediatric-specific research through the 7th Framework Programme (7FP) of the European Union.

  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. Pharmacokinetics of SPECT radiopharmaceuticals for imaging hypoxic tissues.

    Science.gov (United States)

    Wiebe, L I; Stypinski, D

    1996-09-01

    Although hypoxia has been known for decades to play an important role in the outcome of radiotherapy in oncology, and inspite of the contribution of hypoxia to a myriad of pathologies that involve vascular disease, the selective imaging of hypoxic tissue has attained prominence only within the past decade. Contemporary research in the hypoxia imaging field is based largely on radiosensitizer research of the 1960's and 1970's. Early sensitizer research identified a family of nitro-organic compounds, the N-1 substituted 2-nitroimidazoles as candidate drugs. The early champion, and still the reference standard for therapeutic radiosensitization of hypoxic tumor cells is misonidazole (MISO). Its peripheral neurotoxicity led to failure in clinical studies, but its biological, biophysical and biochemical properties have been investigated in detail and serve as a basis for further design, not only of sensitizers, but of diagnostic radiopharmaceuticals for imaging tissue hypoxia. Pharmacokinetic characterization of radiopharmaceuticals, specifically radiopharmaceuticals for imaging tissue hypoxia, has not been a central theme in their development. The advent of PET, through which quantitative determinations first became possible, opened the field for both descriptive and analytical radiopharmacokinetic studies. In SPECT, however, this approach is still undergoing refinement. This paper addresses some of the underlying issues in radiopharmaceutical pharmacokinetics. There is a paucity of published radiopharmacokinetic data for SPECT hypoxia imaging agents. Consequently, the pharmacokinetic issues for MISO are presented as a basis for development of pharmacokinetics for the chemically-related imaging agents. Properties of an hypoxia marker are described from a pharmacokinetic viewpoint, a theoretical model for descriptive pharmacokinetics is introduced and finally, recent pharmacokinetic studies from our laboratory are described.

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

    Science.gov (United States)

    Chang, Zhiwei; Li, Jiguang; Dong, Chenzhong

    2010-12-30

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

  4. 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

  5. Design Features Of Microfluidic Reactor For [18F]FDG Radiopharmaceutical Synthesis

    Science.gov (United States)

    Oh, J. H.; Lee, B. N.; Nam, K. R.; Attla, G. A.; Lee, K. C.; Cjai, J. S.

    2011-06-01

    Microfluidic reactor exhibits advantages for radiopharmaceutical synthesis. Microfluidic chips can reduce the time for radiosynthesis using tiny quantities of chemical compounds. It also has a good heat transfer, performance and provides an integrated system including synthesis, separation, and purification. These advantages make FDG production. So we have designed a microreactor chip which included the whole chemical processing; water evaporation, solvent exchange, radiofluorination and so on. It was designed by using a commercial 3D CAD modeling program CATIA V5, heat transfer performance was analyzed by ANSYS, and CFX was used for analyzing fluid performance. This paper described the design of FDG synthesis system on a microchip, the relevant locations of its parts, both heat and fluid performance efficiency analysis.

  6. GMP compliant radiosynthesis of11C and18F-labeled PET radiopharmaceuticals with a modular disposable cassette system

    NARCIS (Netherlands)

    Hessels-Scheper, J.G.; Maarsingh, P.; Kwizera, C.; Zijlma, R.; Maas, B.; De Vries, A.M.T.; Antunes, I.F.; Lub-de Hooge, M.N.; Boersma, H.H.; Dierckx, R.A.J.O.; De Vries, E.F.J.; Luurtsema, G.; Elsinga, P.H.

    2014-01-01

    Background Many nuclear medicine departments have an extensive radiopharmaceutical portfolio. Consequently, these multiple PET radiopharmaceuticals have to be produced with the same synthesis module. An important consideration in GMP-compliant PET production is to avoid potential cross-contamination

  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. In-vivo behavior of tin-radiopharmaceuticals

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Tin is an essential ingredient of most technetium-99m radiopharmaceuticals but its in-vivo distribution and long-term fate are not well understood. This work describes distribution in mice of several tin-117m labeled compounds. The results indicate that stannic-HEDTMP appears to be the best overall bone localizing agent with very low blood, muscle, kidney, or liver uptake, and its binding to bone is higher than that of tin-117m-DTPA, which make it potentially useful as an agent for skeletal scintigraphy and radiotherapy of bone tumors.

  10. Radiopharmaceuticals introduction to drug evaluation and dose estimation

    CERN Document Server

    Williams, Lawerence E

    2010-01-01

    Nanoengineering, energized by the desire to find specific targeting agents, is leading to dramatic acceleration in novel drug design. However, in this flurry of activity, some issues may be overlooked. This is especially true in the area of determining dosage and evaluating the effects of multiple agents designed to target more than one site of metastasis. Offering the unique perspective of a medical physicist who has worked directly with cancer patients for over three decades, Radiopharmaceuticals: Introduction to Drug Evaluation and Dose Estimation starts by exploring the recent history and

  11. Molecular Engineering of Technetium and Rhenium Based Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Zubieta, J.

    2003-06-30

    The research was based on the observation that despite the extraordinarily rich coordination chemistry of technetium and rhenium and several notable successes in reagent design, the extensive investigations by numerous research groups on a variety of N{sub 2}S{sub 2} and N{sub 3}S donor type ligands and on HYNIC have revealed that the chemistries of these ligands with Tc and Re are rather complex, giving rise to considerable difficulties in the development of reliable procedures for the development of radiopharmaceutical reagents.

  12. A Peltier thermal cycling unit for radiopharmaceutical synthesis

    Energy Technology Data Exchange (ETDEWEB)

    McKinney, C.J.; Nader, M.W

    2001-01-15

    We have investigated the use of Peltier devices to rapidly cycle the temperature of reaction vessels in a radiopharmaceutical synthesis system. Peltier devices have the advantage that they can be actively cooled as well as heated, allowing precise and rapid control of vessel temperatures. Reaction vessel temperatures of between -6 deg. C and 110 deg. C have been obtained with commercially available devices with reasonable cycle times. Two devices have been used as the basis for a general purpose, two-pot synthesis system for production of [{sup 11}C] compounds such as raclopride.

  13. A Peltier thermal cycling unit for radiopharmaceutical synthesis.

    Science.gov (United States)

    McKinney, C J; Nader, M W

    2001-01-01

    We have investigated the use of Peltier devices to rapidly cycle the temperature of reaction vessels in a radiopharmaceutical synthesis system. Peltier devices have the advantage that they can be actively cooled as well as heated, allowing precise and rapid control of vessel temperatures. Reaction vessel temperatures of between -6 degrees C and 110 degrees C have been obtained with commercially available devices with reasonable cycle times. Two devices have been used as the basis for a general purpose, two-pot synthesis system for production of [11C] compounds such as raclopride.

  14. 68Ga-Based Radiopharmaceuticals: Production and Application Relationship

    Directory of Open Access Journals (Sweden)

    Irina Velikyan

    2015-07-01

    Full Text Available The contribution of 68Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This review discusses the key aspects of the production of 68Ga and 68Ga-based radiopharmaceuticals in the light of the impact of regulatory requirements and endpoint pre-clinical and clinical applications.

  15. Guidance for nuclear medicine staff on radiopharmaceuticals drug interaction

    Directory of Open Access Journals (Sweden)

    Ralph Santos-Oliveira

    2009-12-01

    Full Text Available Numerous drug interactions related to radiopharmaceuticals take place every day in hospitals many of which are not reported or detected. Information concerning this kind of reaction is not abundant, and nuclear medicine staff are usually overwhelmed by this information. To better understand this type of reaction, and to help nuclear medicine staff deal with it, a review of the literature was conducted. The results show that almost all of radiopharmaceuticals marketed around the world present drug interactions with a large variety of compounds. This suggests that a logical framework to make decisions based on reviews incorporating adverse reactions must be created. The review also showed that researchers undertaking a review of literature, or even a systematic review that incorporates drug interactions, must understand the rationale for the suggested methods and be able to implement them in their review. Additionally, a global effort should be made to report as many cases of drug interaction with radiopharmaceuticals as possible. With this, a complete picture of drug interactions with radiopharmaceuticals can be drawn.Diversos casos de interações medicamentosas com radiofármacos ocorrem diariamente na rotina hospitalar, contudo muitos deles não são notificados ou mesmo percebidos. Informações a respeito desse tipo de reação não é abundante e os profissionais da medicina nuclear muitas vezes estão assoberbados por essas informações. De modo a entender esse tipo de reação e auxiliar a medicina nuclear a lidar com essa situação uma revisão da literatura foi realizada. Os resultados mostraram que a totalidade dos radiofármacos comercializados no mundo apresentam interação medicamentosa com uma enorme variedade de outros medicamentos. Dessa forma sugere-se que revisões sobre radiofármacos inclua um capítulo sobre efeitos adversos. Além disso, um esforço mundial para notificar efeitos adversos deve ser realizado, pois somente

  16. Basics and principles of radiopharmaceuticals for PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Wadsak, W. [Department of Nuclear Medicine, Medical University of Vienna (Austria); Mitterhauser, M. [Department of Nuclear Medicine, Medical University of Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

    2010-03-15

    The presented review provides general background on PET radiopharmaceuticals for oncological applications. Special emphasis is put on radiopharmacological, radiochemical and regulatory aspects. This review is not meant to give details on all different PET tracers in depth but to provide insights into the general principles coming along with their preparation and use. The PET tracer plays a pivotal role because it provides the basis both for image quality and clinical interpretation. It is composed of the radionuclide (signaller) and the molecular vehicle which determines the (bio-)chemical properties (e.g. binding characteristics, metabolism, elimination rate)

  17. 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.

  18. 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.

  19. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rothe, Sebastian

    2012-09-24

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

  1. 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

  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. 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)

  4. 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)

  5. 86Y based PET radiopharmaceuticals: radiochemistry and biological applications.

    Science.gov (United States)

    Nayak, Tapan K; Brechbiel, Martin W

    2011-09-01

    Development of targeted radionuclide therapy with (90)Y labeled antibodies and peptides has gained momentum in the past decade due to the successes of (90)Y-ibritumomab tiuxetan and (90)Y-DOTA-Phe(1)-Tyr(3)-octreotide in treatment of cancer. (90)Y is a pure β(-)-emitter and cannot be imaged for patient-specific dosimetry which is essential for pre-therapeutic treatment planning and accurate absorbed dose estimation in individual patients to mitigate radiation related risks. This review article describes the utility of (86)Y, a positron emitter (33%) with a 14.7-h half-life that can be imaged by positron emission tomography and used as an isotopically matched surrogate radionuclide for (90)Y radiation doses estimations. This review discusses various aspects involved in the development of (86)Y labeled radiopharmaceuticals with the specific emphasis on the radiochemistry and biological applications with antibodies and peptides.

  6. New selenium-75 labeled radiopharmaceuticals: selenonium analogues of dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Sadek, S.A.; Basmadjian, G.P.; Hsu, P.M.; Rieger, J.A.

    1983-07-01

    Selenium-75 labeled selenonium analogues of dopamine, (2-(3,4-dimethoxyphenyl)ethyl)dimethylselenonium iodide and its dihydroxy analogue, were prepared by reducing (/sup 75/Se)selenious acid with sodium borohydride at pH 6.0 and reacting the NaSeH produced with 1-(3,4-dimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethane. Tissue distribution studies in rats given the /sup 75/Se-labeled selenonium agents intravenously demonstrated high initial heart uptake. Prolonged adrenal retention and high adrenal to blood ratio of compound 4 were observed. The high uptake and adrenal to blood ratio suggest the potential use of compound 4 as a radiopharmaceutical for the adrenal gland.

  7. Receptor-binding radiotracers: a class of potential radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Eckelman, W.C.; Reba, R.C.; Gibson, R.E.; Rzeszotarski, W.J.; Vieras, F.; Mazaitis, J.K.; Francis, B.

    1979-04-01

    To date no radiopharmaceutical is routinely used to study changes in receptor concentration. Frequently changes in receptor concentration, or the appearance of receptors in tumors, indicates a specific pathologic state. With a receptor-binding radiotracer, in vivo studies of these changes will be possible. A reversible bimolecular model and in vitro tests were used to determine equilibrium constants and maximal target-to-blood ratios for new derivatives. Theoretical calculations showed that derivatives binding to the estrogen receptor, the beta adrenoceptor, or the cholinergic receptor are capable of achieving satisfactory target-to-blood ratios. Using in vitro tests, the apparent affinity constant was determined for five iodinated estrogen derivatives and five derivatives of beta blockers. Results of the in vitro study with derivatives of beta blockers. Results of the in vitro study with derivatives of beta blockers, and in vivo displacement studies using propranolol, indicated that the high heart-to-blood ratios (5 to 20) obtained with the new derivatives were not the result of a specific interaction with the receptor. In this instance factors other than receptor binding control the in vivo distribution. The in vitro assay using estrogen receptors showed that of the five derivatives, iodohexestrol and 17-alpha-iodoethynylestradiol bind to the receptor with the highest affinity. In vivo studies confirmed these results; iodohexestrol gave a uterus-to-blood ratio of 10 in immature rats when plasma-protein binding was blocked. With a tritiated muscarinic cholinergic blocking agent, heart-to-blood ratios near the theoretical maximum were obtained. This compound most closely follows the mechanism described by the model. Use of the theoretical model in conjunction with in vitro assays can greatly aid in the design of this new class of receptor-binding radiopharmaceuticals.

  8. 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

  9. 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. T

  10. 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.

  11. Investigation using an advanced extremity gamma instrumentation system of options for shielding the hand during the preparation and injection of radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Whitby, M; Martin, C J [Health Physics, Department of Clinical Physics and Bio-Engineering, Western Infirmary, Glasgow G11 6NY (United Kingdom)

    2003-03-01

    Staff preparing and injecting radiopharmaceuticals in hospitals may receive significant radiation doses to their hands. These doses may be high enough to warrant that they be classified as radiation workers. The influence of local shielding on finger doses has been investigated. Staff preparing radioactive liquids in a radionuclide dispensary and drawing up and injecting radiopharmaceuticals in a nuclear medicine department have been studied. Measurements have been recorded with an electronic extremity dose monitor, an advanced extremity gamma instrumentation system (AEGIS), worn near to the finger tip. The electronic dosimeter allows the pattern of doses received during different procedures to be determined. Doses received for individual manipulations during many routine sessions have been recorded for different staff members. Dose distributions around shielded vials and syringes have also been measured using AEGIS. In the radionuclide dispensary the vials from which radioactive liquids are dispensed are held in tungsten shields, whereas in nuclear medicine simple lead pots are used. Syringe shields are employed for some parts of dispensing and patient injections. Data on dose distributions have been used in interpretation of results from monitoring. Use of syringe shields during dispensing reduced the finger dose by 75-85%. The peaks in dose rate were 60% lower, and periods of exposure to high dose rates were reduced in length by a third because of the restriction in the region of high dose rate. The extremity doses to staff dispensing and injecting radiopharmaceuticals in nuclear medicine were of similar magnitude. Doses received during dispensing varied from 10 to 555 {mu}Gy depending upon whether the vial containing the radiopharmaceutical was directly handled or not. Dose received from individual injections varied from 1 to 150 {mu}Gy depending on the degree of difficulty experienced during the injection.

  12. Investigation using an advanced extremity gamma instrumentation system of options for shielding the hand during the preparation and injection of radiopharmaceuticals.

    Science.gov (United States)

    Whitby, M; Martin, C J

    2003-03-01

    Staff preparing and injecting radiopharmaceuticals in hospitals may receive significant radiation doses to their hands. These doses may be high enough to warrant that they be classified as radiation workers. The influence of local shielding on finger doses has been investigated. Staff preparing radioactive liquids in a radionuclide dispensary and drawing up and injecting radiopharmaceuticals in a nuclear medicine department have been studied. Measurements have been recorded with an electronic extremity dose monitor, an advanced extremity gamma instrumentation system (AEGIS), worn near to the finger tip. The electronic dosimeter allows the pattern of doses received during different procedures to be determined. Doses received for individual manipulations during many routine sessions have been recorded for different staff members. Dose distributions around shielded vials and syringes have also been measured using AEGIS. In the radionuclide dispensary the vials from which radioactive liquids are dispensed are held in tungsten shields, whereas in nuclear medicine simple lead pots are used. Syringe shields are employed for some parts of dispensing and patient injections. Data on dose distributions have been used in interpretation of results from monitoring. Use of syringe shields during dispensing reduced the finger dose by 75-85%. The peaks in dose rate were 60% lower, and periods of exposure to high dose rates were reduced in length by a third because of the restriction in the region of high dose rate. The extremity doses to staff dispensing and injecting radiopharmaceuticals in nuclear medicine were of similar magnitude. Doses received during dispensing varied from 10 to 555 microGy depending upon whether the vial containing the radiopharmaceutical was directly handled or not. Dose received from individual injections varied from 1 to 150 microGy depending on the degree of difficulty experienced during the injection.

  13. 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)

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Claesson, Kristina

    2011-05-15

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

  16. Use of radiopharmaceuticals in diagnostic nuclear medicine in the United States: 1960-2010.

    Science.gov (United States)

    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

    2015-05-01

    To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors 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 diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists' cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations.

  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. 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

  19. 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.

  20. 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.

  1. The next generation of positron emission tomography radiopharmaceuticals in oncology.

    Science.gov (United States)

    Rice, Samuel L; Roney, Celeste A; Daumar, Pierre; Lewis, Jason S

    2011-07-01

    Although (18)F-fluorodeoxyglucose ((18)F-FDG) is still the most widely used positron emission tomography (PET) radiotracer, there are a few well-known limitations to its use. The last decade has seen the development of new PET probes for in vivo visualization of specific molecular targets, along with important technical advances in the production of positron-emitting radionuclides and their related labeling methods. As such, a broad range of new PET tracers are in preclinical development or have recently entered clinical trials. The topics covered in this review include labeling methods, biological targets, and the most recent preclinical or clinical data of some of the next generation of PET radiopharmaceuticals. This review, which is by no means exhaustive, has been separated into sections related to the PET radionuclide used for radiolabeling: fluorine-18, for the labeling of agents such as FACBC, FDHT, choline, and Galacto-RGD; carbon-11, for the labeling of choline; gallium-68, for the labeling of peptides such as DOTATOC and bombesin analogs; and the long-lived radionuclides iodine-124 and zirconium-89 for the labeling of monoclonal antibodies cG250, and J591 and trastuzumab, respectively.

  2. Uptake of SPECT radiopharmaceuticals in neocortical brain cultures

    Energy Technology Data Exchange (ETDEWEB)

    Jong, B.M. de; Royen, E.A. van

    1989-01-01

    The uptake, retention and uptake antagonism of /sup 201/Tl-DDC, /sup 201/Tl-Cl, /sup 123/I-IMP, /sup 99m/Tc-HMPAO and /sup 99m/Tc-O4/sup -/ were compared in rat neocortex cultures. /sup 201/Tl-DDC and /sup 123/I-IP revealed the highest uptake of radioactivity in the cultures. /sup 99m/Tc-HMPAO and /sup 123/I-IMP showed the highest retention of radioactivity within the tissue in washout experiments. Blocking of bioelectric activity by tetrodotoxin did not significantly affect the uptake of the radiopharmaceuticals (RPHA). Inhibition of Na K ATPase by ouabain inhibited the uptake of /sup 201/Tl-Cl (77%) and /sup 201/Tl-DDC (27%). Imipramine showed a significantly stronger inhibitory effect on /sup 123/I-IMP uptake in comparison with the effect on other RPHA. /sup 99m/Tc-O4/sup -/ was not concentrated within the cultured tissue. Under the in vitro conditions used in this study, the various RPHA were characterised by distinct differences in their interaction with cortical brain tissue.

  3. New SPECT and PET Radiopharmaceuticals for Imaging Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Oyebola O. Sogbein

    2014-01-01

    Full Text Available Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT myocardial perfusion imaging (MPI with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET and magnetic resonance imaging (MRI continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed.

  4. 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

  5. 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

    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

  6. 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

  7. Incorporation of radiohalogens via versatile organometallic reactions: applications in radiopharmaceutical chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, P.C.; Goodman, M.M.; Knapp, F.F. Jr.

    1985-01-01

    Factors that must be considered for the design of radiohalogenated radio-pharmaceuticals include the stability and availability of the substrate, the physical half-life of the radiohalogen and the in vivo stability of the radiolabel. Vinyl and phenyl radiohalogen bonds show more in vivo stability than the alkyl radiohalogen bonds. Consequently, a variety of methods suitable for the synthesis of tissue specific radiopharmaceuticals bearing a vinyl or phenyl radiohalogen have been developed involving the synthesis and halogenation of metallovinyl and phenyl intermediates. The halogens and metallation reactions include iodine and bromine and alanation, boronation, mercuration, stannylation, and thallation, respectively. 19 refs., 1 fig., 1 tab.

  8. 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.

  9. 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.

  10. 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.

  11. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2015-07-01

    Full Text Available Objective(s: Peptide Receptor Radionuclide Therapy (PRRT with yttrium-90 (90Y and lutetium-177 (177Lu-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany. Sterile, GMP-certified, no-carrier added (NCA 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods.Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05% and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5% for this period.Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

  12. 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.

  13. 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)

  14. SPECT radiopharmaceuticals for imaging chronic inflammatory diseases in the last decade

    NARCIS (Netherlands)

    Anzola Fuentes, Luz; Galli, F.; Dierckx, R. A.

    2015-01-01

    In the recent years, many radiopharmaceuticals have been described for the diagnosis of inflammatory chronic diseases. Several peptides receptor ligands and monoclonal antibodies have been radiolabelled, allowing in-vivo visualization of inflammatory processes at a cellular and molecular level. The

  15. 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)

  16. 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)

  17. Current status of production and research of radioisotopes and radiopharmaceuticals in Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Soenarjo, Sunarhadijoso; Tamat, Swasono R. [Center for Development of Radioisotopes and Radiopharmaceuticals, National Nuclear Energy Agency (BATAN), Kawasan Puspiptek, Serpong, Tangerang (Indonesia)

    2000-10-01

    The use of radioactive preparation in Indonesia has sharply increased during the past years, indicated by increase of the number of companies utilizing radioisotopes during 1985 to 1999. It has been clearly stressed in the BATAN's Strategic Plan for 1994-2014 that the production of radioisotopes and radiopharmaceuticals is one of five main industrial fields within the platform of the Indonesian nuclear industry. Research programs supporting the production of radioisotopes and radiopharmaceuticals as well as development of production technology are undertaken by the Research Center for Nuclear Techniques (RCNT) in Bandung and by the Radioisotope Production Center (RPC) in Serpong, involving cooperation with other research center within BATAN, universities and hospitals as well as overseas nuclear research institution. The presented paper describes production and research status of radioisotopes and radiopharmaceuticals in Indonesia after the establishment of P.T. Batan Teknologi in 1996, a government company assigned for activities related to the commercial application of nuclear technology. The reviewed status is divided into two short periods, i.e. before and after the Chairman Decree No. 73/KA/IV/1999 declaring new BATAN organizational structure. Subsequent to the Decree, all commercial requests for radioisotopes and radiopharmaceuticals are fulfilled by P.T. Batan Teknologi, while demands on novel radioactive preparations or new processing technology, as well as research and development activities should be fulfilled by the Center for the Development of Radioisotopes and Radiopharmaceuticals (CDRR) through non-commercial arrangement. The near-future strategic research programs to response to dynamic public demand are also discussed. The status of research cooperation with JAERI (Japan) is also reported. (author)

  18. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

    Science.gov (United States)

    Lange, Rogier; Ter Heine, Rob; Knapp, Russ Ff; de Klerk, John M H; Bloemendal, Haiko J; Hendrikse, N Harry

    2016-10-01

    Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents.

  19. 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.)

  20. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Wilbur, D., Scott

    2011-12-14

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Ryuji [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: nakaor@nirs.go.jp; Furutsuka, Kenji [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Sumitomo Accelerator Service, Tokyo 141-8686 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180 (Japan); Suzuki, Kazutoshi [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2008-10-15

    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 [{sup 18}F]FDG samples. These methods could be applied successfully to the analysis of PET radiopharmaceuticals with ultra-high specific radioactivity.

  3. 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.

  4. 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.

  5. Radiopharmaceutical: options to marketing authorization; Le medicament radiopharmaceutique: les alternatives a l'AMM

    Energy Technology Data Exchange (ETDEWEB)

    Guilloteau, D.; Valat, Ch. [Centre Hospitalier Regional Universitaire, Service Medecine Nucleaire In Vitro, INSERM U 619, 37 - Tours (France); Verbruggen, A. [University Hospital Gasthuisberg, Lab. of Radiopharmaceutical Chemistry, Leuven (Belgium)

    2005-04-15

    In France, since the law 92-1279 (December 1992) the tracer used in nuclear medicine are considered as medicines, and all the regulations applicable to general medicines have to be followed for radiopharmaceuticals. The best situation in order to use radiopharmaceutical in nuclear medicine center is to use a tracer with a marketing authorization. However due to the very high cost to obtain this authorization, many tracers validated by scientific community will never been sold by pharmaceutical companies. However in respect with legal rules, it is possible to prepare these tracers in the hospital radiopharmacy, under the responsibility of the radio-pharmacist. We discuss here these different possibilities (magistral preparation...) and the conditions for these preparations. (author)

  6. Potential synergistic implications for stromal-targeted radiopharmaceuticals in bone-metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor

    2011-01-01

    Genetic heterogeneity and chemotherapy-resistant 'stem cells' represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this process.

  7. Radiochemistry on chip: towards dose-on-demand synthesis of PET radiopharmaceuticals.

    Science.gov (United States)

    Arima, Valentina; Pascali, Giancarlo; Lade, Oliver; Kretschmer, Hans R; Bernsdorf, Ingo; Hammond, Victoria; Watts, Paul; De Leonardis, Francesco; Tarn, Mark D; Pamme, Nicole; Cvetkovic, Benjamin Z; Dittrich, Petra S; Vasovic, Nikola; Duane, Russell; Jaksic, Aleksandar; Zacheo, Antonella; Zizzari, Alessandra; Marra, Lucia; Perrone, Elisabetta; Salvadori, Piero A; Rinaldi, Rosaria

    2013-06-21

    We have developed an integrated microfluidic platform for producing 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) in continuous flow from a single bolus of radioactive isotope solution, with constant product yields achieved throughout the operation that were comparable to those reported for commercially available vessel-based synthesisers (40-80%). The system would allow researchers to obtain radiopharmaceuticals in a dose-on-demand setting within a few minutes. The flexible architecture of the platform, based on a modular design, can potentially be applied to the synthesis of other radiotracers that require a two-step synthetic approach, and may be adaptable to more complex synthetic routes by implementing additional modules. It can therefore be employed for standard synthesis protocols as well as for research and development of new radiopharmaceuticals.

  8. Structure biodistribution relationship of radiolabeled ergolines: search for brain imaging radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Basmadjian, G.P.; Sadek, S.A.; Mikhail, E.A.; Parikh, A.; Weaver, A.; Mills, S.L. (Oklahoma Univ., Oklahoma City, OK (USA). Medical Center)

    1989-08-01

    A series of ergoline derivatives, analogues of Pergolide and Lysergol were synthesized, radiolabeled with {sup 125}I or {sup 75}Se, and evaluated for their ability to cross the Blood Brain Barrier of rats, for potential use as radiopharmaceuticals for imaging the brain. Introduction of the radiolabel was either at the 17- position (attached to the 8{beta}-methylene) or at the 2- position of the indole portion of the ergoline moiety. Of the 8 radiolabeled compounds tested, two pergoline analogues, 8{beta}-(methyl-{sup 75}Se-seleno)-methyl-6-propyl ergoline and 8{beta}-({sup 125}I)-iodomethyl-6-propyl ergoline, showed the highest uptake in the brain, adrenal and heart with good organ to blood ratios. This work has shown that analogues of pergolide, a dopamine agonist, if labeled with {sup 123}I may yield a clinically useful brain imaging radiopharmaceutical. (author).

  9. Detection of sentinel lymphnode using radiopharmaceuticals methods, importance and safety handling

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Kunihiko; Nakajima, Kenichi; Tonami, Norihisa; Tugawa, Koichiro; Noguchi, Masakuni [Kanazawa Univ. (Japan). Hospital

    2000-04-01

    In our district, there is no approved radiopharmaceutical appropriate for lymphoscintigraphy. Thus, we have attempted to evaluate the three radiopharmaceuticals such as {sup 99m}Tc-human serum albumin (HSA), {sup 99m}Tc-tin colloid (TC) and {sup 99m}Tc-phytate for this application. HSA demonstrated the sentinel LNs in 35 out 49 cases. However, it traveled so rapid that LNs might tend to be visualized more than the sentinel LN. TC was so big in size that it could only visualize the sentinel LNs in 18 out of 33 cases. Although the number of patients who received phytate is limited, it seemed to detect sentinel LNs better that the other 2 compounds. (author)

  10. Radiopharmaceutical stannic Sn-117m chelate compositions and methods of use

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Suresh C. (Setauket, NY); Meinken, George E. (Middle Island, NY)

    2001-01-01

    Radiopharmaceutical compositions including .sup.117m Sn labeled stannic (Sn.sup.4+) chelates are provided. The chelates are preferably polyhydroxycarboxylate, such as oxalates, tartrates, citrates, malonates, gluconates, glucoheptonates and the like. Methods of making .sup.117m Sn-labeled (Sn.sup.4+) polyhydroxycarboxylic chelates are also provided. The foregoing pharmaceutical compositions can be used in methods of preparing bone for scintigraphical analysis, for radiopharmaceutical skeletal imaging, treatment of pain resulting from metastatic bone involvement, treatment of primary bone cancer, treatment of cancer resulting from metastatic spread to bone from other primary cancers, treatment of pain resulting from rheumatoid arthritis, treatment of bone/joint disorders and to monitor radioactively the skeletal system.

  11. 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.

  12. A Study on the Quality Control of {sup 18}F-FDG Radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ssang Tae [CareCamp Inc., Seoul (Korea, Republic of); Yong, Chul Soon [Yeungnam University, Gyeongsan (Korea, Republic of); Han, Eun Ok [Daegu Health College, Daegu (Korea, Republic of)

    2010-12-15

    The types of test items which were recorded in this test report of quality control domestic {sup 18}F-FDG radiopharmaceutical which consisted of 13 different types: appearance, half-life, radioactive heterokaryosis, radiochemical Confirmation (measure of Rf value), radiochemical Purity, Ethanol, Acetonitrile, Kryptofix, Aluminium, pH, Endotoxin, aseptic test, and radioactivity·ml-1. The record was fully recorded in 'appearance', 'radioactive heterokaryosis', 'pH', 'Endotoxin', and 'aseptic test'. In 'half-life', 'radiochemical Confirmation (measure of Rf value), 'radiochemical Purity', 'Ethanol', 'Acetonitrile', 'Kryptofix', 'Aluminium', 'radioactivity·ml-1', there were differences in records of each manufacturing business on radioactive medicine and medical supplies. The result of the test showed all 13 items of quality control test were 100% suitable on the basis of recorded data. There were more radiopharmaceutical made in the laboratory than in hospitals and businesses and in for result of suitability test, the laboratory showed higher suitability than did the hospitals or businesses. Domestically, there are differences of the test report items in the safety of radiopharmaceutical of each facility, and since it is not standardized, supplements are needed. To submit standardized test reports of quality guarantee in radiopharmaceutical, GMP of U.S. and CE Mark of Europe should be referred as well as receiving advice from professionals to standardize as suitable domestic standard.

  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. 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)

  15. 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.

  16. 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.

  17. 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.

  18. Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing.

    Science.gov (United States)

    Belanger, Anthony P; Byrne, John F; Paolino, Justin M; DeGrado, Timothy R

    2009-11-01

    The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [(18)F]FDG and [(11)C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).

  19. Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Belanger, Anthony P.; Byrne, John F.; Paolino, Justin M. [Brigham and Women' s Hospital, Boston, MA 02115 (United States); DeGrado, Timothy R. [Brigham and Women' s Hospital, Boston, MA 02115 (United States)], E-mail: tdegrado@partners.org

    2009-11-15

    The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [{sup 18}F]FDG and [{sup 11}C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells)

  20. 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

  1. 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

  2. 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

  3. 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

  4. The relationship between administered radiopharmaceutical activity in myocardial perfusion scintigraphy and imaging outcome

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, C.N.; Aswegen, A. van; Tout, D.A. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Julious, S.A. [University of Sheffield, Sheffield (United Kingdom); Nunan, T.O. [Guy' s and St Thomas' Hospital NHS Trust, London (United Kingdom); Thomson, W.H. [Sandwell and West Birmingham Hospitals NHS Trust, Birmingham (United Kingdom); Tindale, W.B. [Sheffield Teaching Hospitals, Sheffield (United Kingdom); Underwood, S.R. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Imperial College London, London (United Kingdom); Royal Brompton Hospital, London (United Kingdom)

    2008-02-15

    Lower radiopharmaceutical activities are used for myocardial perfusion scintigraphy (MPS) in the UK than in other countries. There is no evidence to suggest that higher activities improve imaging or clinical outcome. We undertook a multicentre study of the relationship between radiopharmaceutical activity and imaging outcome. Fifty-one patients with clinical referrals for MPS followed a 2-day protocol with an injection of 1,000 MBq {sup 99m}Tc-tetrofosmin for each of the stress and rest images. ECG-gated acquisition was performed in three rotations occupying 25, 35 and 40% of a standard acquisition, and rotations were summed to simulate administered activities of 250, 400, 750 and 1,000 MBq. Each set of images was reported by an experienced physician who was blinded to all clinical information and to the simulated activity. Scores were assigned for image quality, low count, attenuation and reconstruction artefact, segmental tracer uptake, segmental and global defect classification, and confidence in the global classification. The images were reported twice to assess intra-observer variability. Positive relationships were found between administered activity and overall image quality, observer confidence and intra-observer agreement of uptake score, and a negative relationship was found with low-count artefact. For the majority of comparisons, there was no additional improvement with increasing activity from 750 to 1,000 MBq. Intra-observer agreement was found to be better in female patients and in those below average body mass index. We conclude that higher administered radiopharmaceutical activities lead to better quality images and improved surrogate parameters for clinical outcome, but that activities above 750 MBq may be unnecessary in average patients. (orig.)

  5. 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)

  6. Knowledge evaluation for knowledge management implementation: A case study of the radiopharmaceutical centre of IPEN

    Energy Technology Data Exchange (ETDEWEB)

    Ricciardi, R.I. [Instituto de Pesquisas Energeticas e Nucleares, Nuclear and Energy Research Institute, IPEN-Brazil, Cidade Universitaria, Sao Paulo, SP (Brazil)]. E-mail: rita@ipen.br; Barroso, A.C.O. [Instituto de Pesquisas Energeticas e Nucleares, Nuclear and Energy Research Institute, IPEN-Brazil, Cidade Universitaria, Sao Paulo, SP (Brazil)]. E-mail: barroso@ipen.br; Ermine, J.-L. [INT - Institut National des Telecommunications, Evry Cedex (France)]. E-mail: jean-louis.ermine@int-evry.fr

    2006-07-01

    In recent years, organisations have used multiple methods and approaches to design their strategic and action plans. In this context, resource-based view (RBV) and knowledge-based view (KBV) frameworks have received increased attention as being instrumental to strategy formulation. The synergy of these approaches with knowledge management initiatives is intuitive and their use in a common framework is discussed here to show the importance of methods and instruments to mapping and assessing the knowledge assets of an organisation. The application of such methods to the radiopharmaceutical centre of IPEN is described. (author)

  7. {sup 18}F-labeled radiopharmaceuticals for PET in oncology, excluding FDG

    Energy Technology Data Exchange (ETDEWEB)

    Varagnolo, L.; Stokkel, M.P.M.; Mazzi, U.; Pauwels, E.K.J

    2000-02-01

    This article reviews possible use of {sup 18}F-labelled radiopharmaceuticals in oncology with positron emission tomography. The characteristics of various {sup 18}F-labelled compounds are proteins and peptides, those that bind to {center_dot} receptors, agents to assess hypoxia, and agents to evaluate gene therapy are highlighted. Furthermore, different {sup 18}F-labelled tissue specific agents are indicated for the detection and monitoring of various malignancies: melanoma, brain tumours, breast cancer, prostate cancer and colorectal cancer. {sup 18}F-fluorodeoxyglucose has been excluded from this summary.

  8. Localization of placenta in scanning by /sup 113m/In radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Cho, O.K.; Oh, K.K.; Park, C.Y.; Choi, B.S.; Ha, C.H.; Chung, S.O.; Kwak, H.M.

    1975-01-01

    Placenta previa is a common grave complication of late pregnancy, usually manifestated clinically by painless antenatal vaginal bleeding. Digital and rectal examinations are dangerous, due to the possibility that profuse hemorrhage from the vagina may result. Various radiological examinations have been performed in placenta previa for diagnosis and localization. However radioisotopic methods are superior due to safety, simplicity and a lower radiation dose, both fetal and maternal, compared to plain radiography. Among radiopharmaceuticals, In/sup 113m/ (transferrin for blood pool scan) is useful, giving more satisfactory results without any complications or untoward reactions.

  9. 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.

  10. 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)

  11. Evaluation of quality control of radiopharmaceuticals in Nuclear Medicine service; Avaliacao do controle de qualidade de radiofarmacos em servico de medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, Jamille A. Lopes; Lira, Renata F. de, E-mail: jam_alt@hotmail.com, E-mail: renatafariasdelira@hotmail.com [Universidade Federal de Pernambuco (UFPE), Recife (Brazil); Santos, Marcus Aurelio P. dos, E-mail: masantos@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2014-07-01

    Radiopharmaceuticals are a type of pharmaceutical preparation associated with radionuclides with purpose of diagnosis and therapy. Nuclear Medicine Services (NMS) should perform quality control of radiopharmaceuticals according to the recommendations of the manufacturer and scientific evidences accepted by the National Agency Sanitary Surveillance ( Brazilian ANVISA). This study evaluated the quality of the main radiopharmaceuticals in a NMS of the state of Pernambuco in relation to pH and radiochemical purity. The results showed that 96.8% of the radiopharmaceuticals showed radiochemical purity and all pH values were within the range recommended by the American pharmacopoeia. The study found that the quality control when inserted into the NMS, provides important data that allows exclusion of radiopharmaceuticals with low radiochemistry purity, favoring a reliable diagnosis and ensuring good radiation protection practices and biosecurity for patient and occupationally exposed individuals.

  12. 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.

  13. 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.

  14. Comparative evaluation of glutamate-sensitive radiopharmaceuticals: Technetium-99m-glutamic acid and technetium-99m-diethylenetriaminepentaacetic acid-bis(glutamate) conjugate for tumor imaging.

    Science.gov (United States)

    Kakkar, Dipti; Tiwari, Anjani K; Chuttani, Krishna; Kaul, Ankur; Singh, Harpal; Mishra, Anil K

    2010-12-01

    Single-photon emission computed tomography has become a significant imaging modality with huge potential to visualize and provide information of anatomic dysfunctions that are predictive of future diseases. This imaging tool is complimented by radiopharmaceuticals/radiosubstrates that help in imaging specific physiological aspects of the human body. The present study was undertaken to explore the utility of technetium-99m (⁹⁹(m)Tc)-labeled glutamate conjugates for tumor scintigraphy. As part of our efforts to further utilize the application of chelating agents, glutamic acid was conjugated with a multidentate ligand, diethylenetriaminepentaacetic acid (DTPA). The DTPA-glutamate conjugate [DTPA-bis(Glu)] was well characterized by IR, NMR, and mass spectroscopy. The biological activity of glutamic acid was compared with its DTPA conjugate by radiocomplexation with ⁹⁹(m)Tc (labeling efficiency ≥98%). In vivo studies of both the radiolabeled complexes ⁹⁹(m)Tc-Glu and ⁹⁹(m)Tc-DTPA-bis(Glu) were then carried out, followed by gamma scintigraphy in New Zealand albino rabbits. Improved serum stability of ⁹⁹(m)Tc-labeled DTPA conjugate indicated that ⁹⁹(m)Tc remained bound to the conjugate up to 24 hours. Blood clearance showed a relatively slow washout of the DTPA conjugate when compared with the labeled glutamate. Biodistribution characteristics of the conjugate in Balb/c mice revealed that DTPA conjugation of glutamic acid favors less accumulation in the liver and bone and rapid renal clearance. Tumor scintigraphy in mice showed increasing tumor accumulation, stable up to 4 hours. These preliminary studies show that ⁹⁹(m)Tc-DTPA-bis(Glu) can be a useful radiopharmaceutical for diagnostic applications in single-photon emission computed tomography imaging.

  15. 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.

  16. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Vadim Bernard-Gauthier

    2014-01-01

    Full Text Available Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET. These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014 shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry.

  17. Evaluation of a measurement system for Uranium electrodeposition control to radiopharmaceuticals production

    Energy Technology Data Exchange (ETDEWEB)

    Tufic Madi Filho; Adonis Marcelo Saliba Silva; Jose Patricio Nahuel Cardenas; Maria da Conceicao Costa Pereira; Valdir Maciel Lopes; Alexandre, P. S.; Diogo, F. S.; Rafael, T. P.; Vitor, O. A; Anderson, F. L.; Lucas, R. S.; Brianna, S.; Eduardo, L. C. [Nuclear and Energy Research Institute, IPEN-CNEN/SP, Av. Prof. Lineu Prestes 2242 Cid Univers. CEP: 05508-000- Sao Paulo-SP, (Brazil)

    2015-07-01

    For 2016, studies by international bodies forecast a crisis in the supply of Molybdenum ({sup 99}Mo), which is the generator of {sup 99m}Tc, widely used for medical diagnoses and treatments. As a result, many countries are making efforts to prevent this crisis. Brazil is developing the Brazilian Multipurpose Reactor (RMB) project, under the responsibility of the National Nuclear Energy Commission (CNEN). The RMB is a nuclear reactor for research and production of radioisotopes used in the production of radiopharmaceuticals and radioactive sources, broadly used in industrial and research areas in Brazil. Electrodeposition of uranium is a common practice to create samples for alpha spectrometry and this methodology may be an alternative way to produce targets of low enriched uranium (LEU) to fabricate radiopharmaceuticals, as {sup 99}Mo, used for cancer diagnosis. To study the electrodeposition, a solution of 10 mM uranyl nitrate, in 2-propanol, containing uranium enriched to 2.4% in {sup 235}U, with pH = 1, was prepared and measurements with an alpha spectrometer were performed. These studies are justified by the need to produce {sup 99}Mo since, despite using molybdenum in bulk, Brazil is totally dependent on its import. In this project, we intend to obtain a process that may be technologically feasible to control the radiation targets for {sup 99}Mo production. (authors)

  18. 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)

  19. 正电子放射性药物的点击合成%Click synthesis of PET radiopharmaceuticals

    Institute of Scientific and Technical Information of China (English)

    许梅; 匡春香

    2009-01-01

    Increasing attention has been focused on synthesis radiopharmaceuticals for positron emission tomography (PET).The recent years witnessed applications of click chemistry to PET radiopharmaceutical synthesis,because of its distinctive advantages including high speed,yield and stereospecificity under mild conditions.Synthesis of 18F-labeled and 11C-labeled radiopharmaceuticals and intermediates via click chemistry are reviewed.The future trend of click chemistry for the synthesis of PET radiopharmaceutical is prospected.%正电子放射性药物的合成是核技术应用领域的焦点之一.近年来点击化学因其高速、高收率、高选择性和条件温和等优点而应用于正电子放射性药物的合成.本文综述了近年来点击化学在PET药物合成中的研究进展(包括将18F和11C导入药物分子),并展望其发展前景.

  20. 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 re

  1. 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

    2005-01-01

    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 (GM

  2. 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

    , 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...

  3. 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.)

  4. 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)

  5. 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)

  6. Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

    Science.gov (United States)

    Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

    2013-06-01

    In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less

  7. Enantiopure bifunctional chelators for copper radiopharmaceuticals--does chirality matter in radiotracer design?

    Science.gov (United States)

    Singh, Ajay N; Dakanali, Marianna; Hao, Guiyang; Ramezani, Saleh; Kumar, Amit; Sun, Xiankai

    2014-06-10

    It is well recognized that carbon chirality plays a critical role in the design of drug molecules. However, very little information is available regarding the effect of stereoisomerism of macrocyclic bifunctional chelators (BFC) on biological behaviors of the corresponding radiopharmaceuticals. To evaluate such effects, three enantiopure stereoisomers of a copper radiopharmaceutical BFC bearing two chiral carbon atoms were synthesized in forms of R,R-, S,S-, and R,S-. Their corresponding peptide conjugates were prepared by coupling with a model peptide sequence, c(RGDyK), which targets the αvβ3 integrin for in vitro and in vivo evaluation of their biological behaviors as compared to the racemic conjugate. Despite the chirality differences, all the conjugates showed a similar in vitro binding affinity profile to the αvβ3 integrin (106, 108, 85 and 100 nM for rac-H2-1, RR-H2-1, SS-H2-1, and RS-H2-1 respectively with all p values > 0.05) and a similar level of in vivo tumor uptake (2.72 ± 0.45, 2.60 ± 0.52, 2.45 ± 0.48 and 2.88 ± 0.59 for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 at 1 h p.i. respectively). Furthermore, they demonstrated a nearly identical biodistribution pattern in major organs (e.g. 2.07 ± 0.21, 2.13 ± 0.58, 1.70 ± 0.20 and 1.90 ± 0.46 %ID/g at 24 h p.i. in liver for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively; 1.80 ± 0.46, 2.30 ± 1.49, 1.73 ± 0.31 and 2.23 ± 0.71 at 24 h p.i. in kidneys for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively). Therefore we conclude that the chirality of BFC plays a negligible role in αvβ3-targeted copper radiopharmaceuticals. However, we believe it is still worthwhile to consider the chirality effects of BFCs on other targeted imaging or therapeutic agents.

  8. {sup 90}Y-oxine-ethiodol, a potential radiopharmaceutical for the treatment of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu Junfeng; Haefeli, U.O. E-mail: hafeliu@ccf.org; Sands, Mark; Dong Yonghua

    2003-05-01

    Ethiodol (or lipiodol) is selectively retained in hepatocellular carcinoma and is used as a vehicle to deliver radioactive agents following intraarterial hepatic infusion. We prepared the lipophilic complex {sup 90}Y-oxine with a radiolabeling efficiency of 97.6{+-}1.1%. After extraction into ethiodol, a stability test in serum at 37 deg. C showed that 87.8% of the {sup 90}Y remained ethiodol-bound for 7 days. Bremsstrahlung imaging of a rabbit for 48 h confirmed that the homogeneous mixture of radiolabeled {sup 90}Y-oxine and ethiodol stayed in the targeted liver lobe. This radiopharmaceutical is thus a potential candidate for the treatment of non-resectable liver cancer.

  9. The growing impact of bioorthogonal click chemistry on the development of radiopharmaceuticals.

    Science.gov (United States)

    Zeng, Dexing; Zeglis, Brian M; Lewis, Jason S; Anderson, Carolyn J

    2013-06-01

    Click chemistry has become a ubiquitous chemical tool with applications in nearly all areas of modern chemistry, including drug discovery, bioconjugation, and nanoscience. Radiochemistry is no exception, as the canonical Cu(I)-catalyzed azide-alkyne cycloaddition, strain-promoted azide-alkyne cycloaddition, inverse electron demand Diels-Alder reaction, and other types of bioorthogonal click ligations have had a significant impact on the synthesis and development of radiopharmaceuticals. This review will focus on recent applications of click chemistry ligations in the preparation of imaging agents for SPECT and PET, including small molecules, peptides, and proteins labeled with radionuclides such as (18)F, (64)Cu, (111)In, and (99m)Tc.

  10. 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.

  11. Sentinel node biopsy using two kinds of radiopharmaceuticals in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hisamatsu, Kazutoshi; Ishine, Masahiro; Takiyama, Wataru [Hiroshima City Asa Hospital (Japan)] [and others

    2002-08-01

    Between June 2000 and May 2001, 37 consecutive patients with breast cancer received sentinel node biopsy (SNB) be the gamma-probe method using two kinds of radiopharmaceutical, Tin colloid in 11 patients (T-group) and Phytate in 26 patients (P-group). The differences in their clinical results were evaluated retrospectively. The identification rate of SN in the P-group was superior than that in the T-group (92% vs. 64%). Accuracy and false negative rates in the P-group vs. the T-group were 96% vs. 100% and 17% vs. 0%, respectively. From these results, Phytate was more useful than Tin colloid in the SNB using gamma-probe method for patients with breast cancer. (author)

  12. The role of coordination chemistry in the development of copper and rhenium radiopharmaceuticals.

    Science.gov (United States)

    Donnelly, Paul S

    2011-02-01

    There are several isotopes of copper and rhenium that are of interest in the development of new molecular imaging or radiotherapeutic agents. This perspective article highlights the role of coordination chemistry in the design of copper and rhenium radiopharmaceuticals engineered to selectively target tissue of interest such as cancer cells or pathological features associated with Alzheimer's disease. The coordination chemistry of copper bis(thiosemicarbazone) derivatives and copper macrocyclic complexes is discussed in terms of their potential application as targeted positron emission tomography tracers for non-invasive diagnostic imaging. A range of rhenium complexes with different ligands with rhenium in different oxidation states are introduced and their potential to be translated to new radiotherapeutic agents discussed.

  13. 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)

  14. 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.

  15. Highway accident involving radiopharmaceuticals near Brookhaven, Mississippi on December 3, 1983

    Energy Technology Data Exchange (ETDEWEB)

    Mohr, P.B.; Mount, M.E.; Schwartz, M.W.

    1985-04-01

    A rear-end collision occurred between a passenger automobile and a luggage trailer carrying 84 packages, 76 of which contained radiopharmaceuticals, on US Highway 84 near Brookhaven, Mississippi on the afternoon of December 3, 1983. The purpose of this report is to document the mechanical circumstances of the accident, confirm the nature and quantity of radioactive materials involved, and assess the nature of the physical environment to which the packages were exposed and the response of the packages. The report consists of three major sections. The first deals wth the nature and circumstances of the accident and findings of fact. The second gives an accounting and description of the materials involved and the consequences of their exposure. The third gives an assessment and analysis of the mechanisms of damage and the conclusions which may be drawn from the investigation. 4 refs., 24 figs., 4 tabs.

  16. Development of specific radiopharmaceuticals for infection imaging by targeting infectious micro-organisms.

    Science.gov (United States)

    Ferro-Flores, Guillermina; Ocampo-Garcia, Blanca E; Melendez-Alafort, Laura

    2012-01-01

    Infectious diseases remain a major health problem and cause of death worldwide. A variety of radiopharmaceuticals are used for the imaging of infections and inflammation in the practice of nuclear medicine. Long-term clinical use has shown that the majority of radiolabeled probes cannot distinguish between inflammation and infection. Gallium-67-citrate binds to bacteria, but also to proteins accumulating at both sterile inflammation and bacterial infection sites. Other agents are used to interact with receptors or domains on circulating and infiltrating leukocytes or to label them directly. However, these probes cannot distinguish between infection and inflammation because they are not specific to infectious micro-organisms. This review examines the recent developments and applications of radiolabeled specific agents, such as antiviral drugs, antifungal, antibiotics and antimicrobial peptides, to visualize infectious foci by targeting viruses, fungi or bacteria.

  17. 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.

  18. Image quality and radiopharmaceutical parameters of Indium-111 granulocytes in scintigraphy of inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Arndt, J.W.; Blok, D.; Tjon, R.T.O.; Tham, A.; Pauwels, E.K.J.; Crama-Bohbouth, G.E.; Verspaget, H.W.; Pena, A.S.; Weterman, I.T.; Lamers, C.B.H.W.

    1989-04-01

    This study was undertaken to investigate the influence of various parameters of injected autologous /sup 111/In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: Good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of /sup 111/In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq /sup 111/In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.

  19. 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.

  20. 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.

  1. 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)

  2. 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.

  3. Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17. cap alpha. -methylestradiol in normal and tumor-bearing rats

    Energy Technology Data Exchange (ETDEWEB)

    Feenstra, A.; Vaalburg, W.; Nolten, G.M.J.; Reiffers, S.; Talma, A.G.; Wiegman, T.; van der Molen, H.D.; Woldring, M.G.

    1983-06-01

    Tritiated 17..cap alpha..-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17..cap alpha..-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (K/sub d/ = 1.96 x 10/sup -10/M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 h after injection. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23 to 30% of the uptake in the uterus. Tritiated 17..cap alpha..-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that a 17 ..cap alpha..-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical.

  4. (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization.

    Science.gov (United States)

    Vallabhajosula, Shankar

    2007-11-01

    Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on

  5. 10 CFR Appendix C to Part 20 - Quantities 1 of Licensed Material Requiring Labeling

    Science.gov (United States)

    2010-01-01

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

  6. Analysis of sup 99m Tc-labeled radiopharmaceuticals by high-performance liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Muto, Toshio (Tokyo Metropolitan Isotope Research Center (Japan))

    1990-02-01

    High-performance liquid chromatography (HPLC) equiped with on line radiometric and optical detectors (i.e. radio-HPLC) have been applied to the radiochemical analysis of commonly-used {sup 99m}Tc-radio pharma ceuticals with a view point to check the radiochemical purities of the compounds. Chromatographic conditions were determined by examination of the types of column, mobile phase and pH. An aqueous size-exclusion (Shim-pack Diol-300) and reversed-phase column (Zorbax-ODS) were found to be suitable for {sup 99m}Tc-HSA and the other {sup 99m}Tc-agents, respectively. The analysis of low molecular weight {sup 99m}Tc-agents (e.g. {sup 99m}Tc-DTPA, {sup 99m}Tc-DMSA, {sup 99m}Tc-pyrophosphate, {sup 99m}Tc-phytic acid, {sup 99m}Tc-MDS, {sup 99m}Tc-HMDP) were done by reversed-phaseion pairing chromatography using a optimized mobile phase consisted on a mixture of 50 mM phosphate buffer (pH 7.0) and 2 mM TBA (tetra nbutyl) ammonium hydroxide in 30 % methanol. The mobile phases for analysis of medium molecular weight {sup 99m}Tc-HSA were consisted of a mixture of 50 mM phosphate buffer (ph 7.0) in 30 % methanol, and a mixtures of 1 % SDS (sodium dodecyl sulfonate) in Tris buffer (pH. 7.0), respectively. It was apparent from the radio-chromatograms obtained from these chromatographic conditions, that impurity of {sup 99m}TcO{sub 4} was observed in {sup 99m}Tc-pyrophosphate, {sup 99m}Tc-phytic acid, {sup 99m}Tc-MDP, {sup 99m}Tc-HMDP, and impurities of {sup 99m}Tc-labeled species and {sup 99m}TcO{sub 4}, were observed in {sup 99m}Tc-HIDA, {sup 99m}Tc-HIDA, {sup 99m}Tc-HSA. The radiochemical impurities of the {sup 99m}Tc-radiopharmaceuticals were ranged between 90 and 100 %. From these results, radio-HPLC has been shown to be suitable method for analysis of {sup 99m}Tc-radiopharmaceuticals, with rapidity and excellent precision. (author).

  7. 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.

  8. 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.

  9. 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)

  10. RADIONUCLIDE STUDIES USING TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS OF PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    N. I. Tarassov

    2009-01-01

    Full Text Available Object: to evaluate the efficiency of prostate scintigraphy in the prebioptic diagnosis of prostate cancer (PC.Subjects and methods. Two hundred and two patients with suspected PC underwent comprehensive examination, including 99mTc-technetril prostate scintigraphy and a morphometric study of biopsy material columns. A computer program (official registration certificate No. 2007614475 dated October 24, 2007 was worked out and patented to calculate the intensity of accumulation of radiopharmaceuticals in different portions of the right and left prostate lobes.Results and discussion. When the division index point «pathological focus/background», 1.5; ≤ 1.5, healthy; > 1.5 suspected prostate cancer was used, the sensitivity of prostate scintigraphy was 81.65%; its specificity was 87.1%; the diagnostic effectiveness was 84.37%.Conclusion: The application of prostate scintigraphy can improve indicators for early detection of PC, due to the purposeful detection of the points, enhance the effectiveness of biopsy, and, having more grounds than the early ones, to exclude this disease at the prebioptic stage. The method is noninvasive and can be used to monitor patients with suspected PC.

  11. RADIONUCLIDE STUDIES USING TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS OF PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    N. I. Tarassov

    2014-08-01

    Full Text Available Object: to evaluate the efficiency of prostate scintigraphy in the prebioptic diagnosis of prostate cancer (PC.Subjects and methods. Two hundred and two patients with suspected PC underwent comprehensive examination, including 99mTc-technetril prostate scintigraphy and a morphometric study of biopsy material columns. A computer program (official registration certificate No. 2007614475 dated October 24, 2007 was worked out and patented to calculate the intensity of accumulation of radiopharmaceuticals in different portions of the right and left prostate lobes.Results and discussion. When the division index point «pathological focus/background», 1.5; ≤ 1.5, healthy; > 1.5 suspected prostate cancer was used, the sensitivity of prostate scintigraphy was 81.65%; its specificity was 87.1%; the diagnostic effectiveness was 84.37%.Conclusion: The application of prostate scintigraphy can improve indicators for early detection of PC, due to the purposeful detection of the points, enhance the effectiveness of biopsy, and, having more grounds than the early ones, to exclude this disease at the prebioptic stage. The method is noninvasive and can be used to monitor patients with suspected PC.

  12. 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).

  13. 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)

  14. A Concise Radiosynthesis of the Tau Radiopharmaceutical, [18F]T807

    Science.gov (United States)

    Shoup, Timothy M.; Yokell, Daniel L.; Rice, Peter A.; Jackson, Raul N.; Livni, Eli; Johnson, Keith A.; Brady, Thomas J.; Vasdev, Neil

    2014-01-01

    Fluorine-18 labelled 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([18F]T807) is a potent and selective agent for imaging paired helical filaments of tau (PHF-tau) and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one-step method for the synthesis of [18F]T807 that is broadly applicable for routine clinical production using a GE Tracerlab™ FXFN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert-butyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, as well as new HPLC separation conditions that enable a facile one-step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [18F]fluoride (K[18F]/K222) in DMSO at 130 °C over 10 min, the precursor is concurrently deprotected. Formulated [18F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/μmol (5837 ± 1621 mCi/μmol) at the end of synthesis (60 min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation which we anticipate will facilitate widespread clinical use of [18F]T807. PMID:24339014

  15. Laser stimulation of the acupoint 'Zusanli' (ST.36) on the radiopharmaceutical biodistribution in Wistar rats.

    Science.gov (United States)

    Frederico, Éric H F F; Santos, Ailton A; Sá-Caputo, Danubia C C; Neves, Rosane F; Guimarães, Carlos A S; Chang, Shyang; Bernardo-Filho, Mario

    2016-03-01

    Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the 'Zusanli' acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na(99m)TcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm(2)) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na(99m)TcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/ g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

  16. Tibial lead determination by 99Tcm radiopharmaceutical x-ray fluorescence.

    Science.gov (United States)

    Mountford, P J; Green, S; Bradley, D A; Lewis, A D; Morgan, W D

    1994-04-01

    The feasibility of measuring tibial lead concentration by x-ray fluorescence with an internal 99Tcm labelled bone-seeking radiopharmaceutical was investigated using phantoms containing known values of lead concentration and 99Tcm activity. The minimum detectable concentration (MDC) at two standard deviations based on the counts in the Kalpha1 peak of 10.9 microg Pb ml(-1) was estimated to correspond to an MDC for an individual within a range of approximately 8-15 microg Pb (g bone mineral)(-1) if the counts from all four K x-ray peaks were included. Due to its much greater dose compared to an external source, the MDC of this internal source technique would have to be reduced before it could be used for measurements of occupationally or environmentally exposed individuals other than as an adjunct for a patient undergoing a bone scan. Methods of achieving such a reduction include increasing the acquisition time and the number of HPGE detectors, and optimizing the design of their collimators.

  17. 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)

  18. 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.

  19. Risk assessment and economic impact analysis of the implementation of new European legislation on radiopharmaceuticals in Italy: the case of the new monograph chapter Compounding of Radiopharmaceuticals (PHARMEUROPA, Vol. 23, No. 4, October 2011).

    Science.gov (United States)

    Chitto, Giuseppe; Di Domenico, Elvira; Gandolfo, Patrizia; Ria, Francesco; Tafuri, Chiara; Papa, Sergio

    2013-12-01

    An assessment of the new monograph chapter Compounding of Radiopharmaceuticals has been conducted on the basis of the first period of implementation of Italian legislation on Good Radiopharmaceuticals Practice (NBP) in the preparation of radiopharmaceuticals, in keeping with Decree by the Italian Ministry of Health dated March 30, 2005. This approach is well grounded in the several points of similarity between the two sets of regulations. The impact on patient risk, on staff risk, and on healthcare organization risk, has been assessed. At the same time, the actual costs of coming into compliance with regulations have been estimated. A change risk analysis has been performed through the identification of healthcare-associated risks, the analysis and measurement of the likelihood of occurrence and of the potential impact in terms of patient harm and staff harm, and the determination of the healthcare organization's controlling capability. In order to evaluate the economic impact, the expenses directly related to the implementation of the activities as per ministerial decree have been estimated after calculating the overall costs unrelated to NBP implementation. The resulting costs have then been averaged over the total number of patient services delivered. NBP implementation shows an extremely positive impact on risk management for both patients receiving Nuclear Medicine services and the healthcare organization. With regard to healthcare workers, instead, the implementation of these regulations has a negative effect on the risk for greater exposure and a positive effect on the defense against litigation. The economic impact analysis of NBP implementation shows a 34% increase in the costs for a single patient service. The implementation of the ministerial decree allows for greater detectability of and control over a number of critical elements, paving the way for risk management and minimization. We, therefore, believe that the proposed tool can provide basic

  20. Development of radiopharmaceuticals based on aptamers: selection and characterization of DNA aptamers for CEA

    Energy Technology Data Exchange (ETDEWEB)

    Correa, C.R.; Andrade, A.S.R., E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Augusto-Pinto, L. [BioAptus, Belo Horizonte, MG (Brazil); Goes, A.M., E-mail: goes@icb.ufmg.br [Departamento de Imunologia e Bioquimica. Instituto de Ciencias Biologicas. Universidade Federal de Minas Gerais. Belo Horizonte, MG (Brazil)

    2011-07-01

    Colorectal cancer is among the top four causes of cancer deaths worldwide. Carcinoembryonic antigen (CEA) is a complex intracellular glycoprotein produced by about 90% of colorectal cancers. CEA has been identified as an attractive target for cancer research because of its pattern of expression in the surface cell and its likely functional role in tumorigenesis. Research on the rapid selection of ligands based on the SELEX (systematic evolution of ligands by exponential enrichment) forms the basis for the development of high affinity and high specificity molecules, which can bind to surface determinants of tumour cells, like CEA. The oligonucleotides ligands generated in this technique are called aptamers. Aptamers can potentially find applications as therapeutic or diagnostic tools for many kind of diseases, like a tumor. Aptamers offer low immunogenicity, good tumour penetration, rapid uptake and fast systemic clearance, which favour their application as effective vehicles for radiotherapy. In addition aptamers can be labeled with different radioactive isotopes. The aim of this work was select aptamers binding to the CEA tumor marker. The aptamers are obtained through by SELEX, in which aptamers are selected from a library of random sequences of synthetic DNA by repetitive binding of the oligonucleotides to target molecule (CEA). Analyses of the secondary structure of the aptamers were determined using the m fold toll. Three aptamers were selected to binding assay with target cells. These aptamers were confirmed to have affinity and specific binding for T84 cell line (target cell), showed by confocal imaging. We are currently studying the potential efficacy of these aptamers as targeted radiopharmaceuticals, for use as imaging agents or therapeutic applications. The development of aptamers specific to CEA open new perspectives for colorectal cancer diagnosis and treatment. Acknowledgments: This investigation was supported by the Centro de Desenvolvimento da

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

    Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available.In contrast toβ-emitters,223Radium as a a-emitter has a short path-length.The advantage of the a-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 a-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity.The a emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongslife in castrate resistant prostate cancer patients with wide-spread bone metastatic disease.In a phaseⅢ,randomized,double-blind,placebo-controlled study 921patients with castration-resistant prostate cancer and bone metastases were randomly assigned.The analysis confirmed the 223Radium survival benefit compared to the placebo(median,14.9 mo vs 11.3 mo;P<0.001).In addition,the treatment results in pain palliation and thus,improved quality of life and a delay of skeletal related events.At the same time the toxicity profile of223Radium was favourable.Since May 2013,223Radium dichloride(Xofigo?)is approved by the US Food and Drug Administration.

  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. Analysis of radionuclide concentration in air released through the stack of a radiopharmaceutical production facility based on a medical cyclotron

    Science.gov (United States)

    Giardina, M.; Tomarchio, E.; Greco, D.

    2015-11-01

    Positron emitting radionuclides are increasingly used in medical diagnostics and the number of radiopharmaceutical production facilities have been estimated to be growing worldwide. During the process of production and/or patient administration of radiopharmaceuticals, an amount of these radionuclides might become airborne and escape into the environment. Therefore, the analysis of radionuclide concentration in the air released to the stack is a very important issue to evaluate the dose to the population living around the plant. To this end, sampling and measurement of radionuclide concentration in air released through the stack of a Nuclear Medicine Center (NMC), provided with a cyclotron for radiopharmaceuticals production, must be routinely carried out with an automatic measurement system. In this work is presented the air monitoring system realized at "San Gaetano" NMC at Bagheria (Italy) besides the analysis of the recorded stack relesead air concentration data. Sampling of air was carried out continuously and gamma-ray spectrometric measurement are made on-line and for a short time by using a shielded Marinelli beaker filled with sampled air and a gamma detector. The use of this system allows to have 1440 values of air concentration per day from 2002, year of the start of operation with the cyclotron. Therefore, the concentration values are very many and an analysis software is needed to determine the dose to the population. A comparison with the results of a simulation code based on a Gaussian Plume air dispersion modelling allow us to confirm the no-radiological significance of the stack effluent releases in terms of dose to population and to evaluate possible improvements in the plant devices to reduce the air concentration at stack.

  4. 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.

  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. 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.

  7. 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.

  8. 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.

  9. 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.)

  10. Influence of the Generator in-Growth Time on the Final Radiochemical Purity and Stability of Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    L. Uccelli

    2013-01-01

    Full Text Available At Legnaro laboratories of the Italian National Institute for Nuclear Physics (INFN, a feasibility study has started since 2011 related to accelerated-based direct production of by the 100Mo(p,2n reaction. Both theoretical investigations and some recent preliminary irradiation tests on 100Mo-enriched samples have pointed out that both the / ratio and the specific activity will be basically different in the final accelerator-produced Tc with respect to generator-produced one, which might affect the radiopharmaceutical procedures. The aim of this work was to evaluate the possible impact of different / isomeric ratios on the preparation of different Tc-labeled pharmaceutical kits. A set of measurements with , eluted from a standard 99Mo/ generator, was performed, and results on both radiochemical purity and stability studies (following the standard quality control procedures are reported for a set of widely used pharmaceuticals (i.e., -Sestamibi, -ECD, -MAG3, -DTPA, -MDP, -HMDP, -nanocolloids, and -DMSA. These pharmaceuticals have been all reconstituted with either the first [O4]− eluate obtained from a 99Mo/ generator (coming from two different companies or eluates after 24, 36, 48, and 72 hours from last elution. Results show that the radiochemical purity and stability of these radiopharmaceuticals were not affected up to the value of 11.84 for the / ratio.

  11. 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)

  12. 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)

  13. 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

  14. 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)

  15. Evaluation of novel bifunctional chelates for the development of Cu-64-based radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Cara L. [MDS Nordion, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada)], E-mail: cara.ferreira@mdsinc.com; Yapp, Donald T. [British Columbia Cancer Agency Research Centre, Vancouver, BC, V5Z 1L3 (Canada); Lamsa, Eric [MDS Nordion, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Gleave, Martin [Prostrate Centre at Vancouver General Hospital, Vancouver, BC, V6H 3Z6 (Canada); Bensimon, Corinne [MDS Nordion, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Jurek, Paul; Kiefer, Garry E. [Macrocylics Inc., Dallas, Texas, 75235 (United States)

    2008-11-15

    Background: Currently available bifunctional chelates (BFCs) for attaching Cu-64 to a targeting molecule are limited by either their radiolabeling conditions or in vivo stability. With the goal of identifying highly effective BFCs, we compared the properties of two novel BFCs, 1-oxa-4,7,10-triazacyclododecane-S-5-(4-nitrobenzyl)-4,7,10-triacetic acid (p-NO{sub 2}-Bn-Oxo) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-S-4- (4-nitrobenzyl)-3,6,9-triacetic acid (p-NO{sub 2}-Bn-PCTA), with the commonly used S-2-(4-nitrobenzyl)-1,4,7,10-tetraazacyclododecanetetraacetic acid (p-NO{sub 2}-Bn-DOTA). Methods: p-NO{sub 2}-Bn-DOTA, p-NO{sub 2}-Bn-Oxo and p-NO{sub 2}-Bn-PCTA were each radiolabeled with Cu-64 under various conditions to assess the reaction kinetics and robustness of the radiolabeling. Stability of each Cu-64 BFC complex was evaluated at low pH and in serum. Small animal positron emission tomography imaging and biodistribution studies in mice were undertaken. Results: p-NO{sub 2}-Bn-Oxo and p-NO{sub 2}-Bn-PCTA possessed superior reaction kinetics compared to p-NO{sub 2}-Bn-DOTA under all radiolabeling conditions; >98% radiochemical yields were achieved in <5 min at room temperature even when using near stoichiometric amounts of BFC. Under nonideal conditions, such as low or high pH, high radiochemical yields were still achievable with the novel BFCs. The radiolabeled compounds were stable in serum and at pH 2 for 48 h. The imaging and biodistribution of the Cu-64-radiolabeled BFCs illustrated differences between the BFCs, including preferential clearance via the kidneys for the p-NO{sub 2}-Bn-PCTA Cu-64 complex. Conclusions: The novel BFCs facilitated efficient Cu-64 radiolabeling under mild conditions to produce stable complexes at potentially high specific activities. These BFCs may find wide utility in the development of Cu-64-based radiopharmaceuticals.

  16. 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

  17. The shielding against radiation produced by powder metallurgy with tungsten copper alloy applied on transport equipment for radio-pharmaceutical products

    Energy Technology Data Exchange (ETDEWEB)

    Cione, Francisco C.; Sene, Frank F.; Souza, Armando C. de; Betini, Evandro G.; Rossi, Jesualdo L., E-mail: fceoni@hotmail.com, E-mail: ffsene@hotmail.com, E-mail: armandocirilo@yahoo.com, E-mail: evandrobetini@gmail.com, E-mail: jelrossi@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Rizzuto, Marcia A., E-mail: marizzutto@if.usp.br [Universidade de Sao Paulo (IF/USP), SP (Brazil). Instituto de Fisica

    2015-07-01

    Safety is mandatory on medicine radiopharmaceutical transportation and dependent on radiation shielding material. The focus of the present work is to minimize the use of harmful materials as lead and depleted uranium usually used in packages transportation. The tungsten-copper composite obtained by powder metallurgy (PM) is non-toxic. In powder metallurgy the density and the porosity of the compacted parts depends basically upon particle size distribution of each component, mixture, compacting pressure and sintering temperature cycle. The tungsten-copper composite, when used for shielding charged particles, X-rays, gamma photons or other photons of lower energy require proper interpretation of the radiation transport phenomena. The radioactive energy reduction varies according to the porosity and density of the materials used as shielding. The main factor for radiation attenuation is the cross section value for tungsten. The motivation research factor is an optimization of the tungsten and cooper composition in order to achieve the best linear absorption coefficient given by equation I{sub (x)} = I{sub 0}e{sup (-ux)}. Experiments were conducted to quantify the effective radiation shielding properties of tungsten-copper composite produced by PM, varying the cooper amount in the composite. The studied compositions were 15%, 20% and 25% copper in mass. The Compaction pressure was 270 MPa and the sintering atmosphere was in 1.1 atm in N{sub 2}+H{sub 2}. The sintering temperature was 980 deg C for 2 h. The linear absorption coefficient factor was similar either for the green and the sintered compacts, due the amount of porosity did not affect the radiation attenuation. Thus the sintered was meant for size reduction and mechanical properties enhancement. (author)

  18. 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)

  19. 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 r

  20. 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)

  1. 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.

  2. First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Radiofluorination: Proof of Concept with the Tau Imaging Agent [18F]T807

    Directory of Open Access Journals (Sweden)

    Steven H. Liang

    2014-10-01

    Full Text Available Despite extensive preclinical imaging with radiotracers developed by continuous-flow microfluidics, a positron emission tomographic (PET radiopharmaceutical has not been reported for human imaging studies by this technology. The goal of this study was to validate the synthesis of the tau radiopharmaceutical 7-(6-fluoropyridin-3-yl-5H-pyrido[4,3-b]indole ([18F]T807 and perform first-in-human PET scanning enabled by microfluidic flow chemistry. [18F]T807 was synthesized by our modified one-step method and adapted to suit a commercial microfluidic flow chemistry module. For this proof of concept, the flow system was integrated to a GE Tracerlab FXFN unit for high-performance liquid chromatography purification and formulation. Three consecutive productions of [18F]T807 were conducted to validate this radiopharmaceutical. Uncorrected radiochemical yields of 17 ± 1% of crude [18F]T807 (≈ 500 mCi, radiochemical purity 95% were obtained from the microfluidic device. The crude material was then purified, and > 100 mCi of the final product was obtained in an overall uncorrected radiochemical yield of 5 ± 1% (n = 3, relative to starting [18F]fluoride (end of bombardment, with high radiochemical purity (≥ 99% and high specific activities (6 Ci/μmol in 100 minutes. A clinical research study was carried out with [18F]T807, representing the first reported human imaging study with a radiopharmaceutical prepared by this technology.

  3. Regional intracellular pH shift: a proposed new mechanism for radiopharmaceutical uptake in brain and other tissues.

    Science.gov (United States)

    Kung, H F; Blau, M

    1980-02-01

    This paper proposes a new mechanism for radiopharmaceutical uptake, which may be applicable to a variety of clinical studies. Many tissues and organs have low intracellular pH, either normally or as a result of various metabolic disturbances. We have developed a series of compounds that are neutral and lipid-soluble at blood pH. These molecules can diffuse freely into cells. In those regions where intracellular pH is low, they pick up a hydrogen ion and become charged. In this form they are no longer lipid-soluble and are trapped because they cannot diffuse out of the cell. Studies of the brain uptake of two compounds of this type, Se-75 labeled di-beta-(morpholinoethyl)-selenide (MOSE) and di-beta-(piperidinoethyl)-selenide (PIPSE), demonstrate the application of the principle.

  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. Food and Drug Administration process for development and approval of drugs and radiopharmaceuticals: treatments in urologic oncology.

    Science.gov (United States)

    Ning, Yang-Min; Maher, V Ellen

    2015-03-01

    Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and Drug Administration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies. This review provides general information about the FDA's role in the development of investigational new drugs, with an emphasis on the regulatory process and the requirements for marketing approval. In addition, this review summarizes the products for the treatment of urologic malignancies that were approved by the FDA in the last 30 years and the key issues concerning urologic oncology products that were discussed publicly at Oncologic Drug Advisory Committee meetings in the past 10 years.

  6. 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

  7. 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.

  8. Fully automatic, microprocessor-controlled system for the production of /sup 11/CO/sub 2/, /sup 11/CH/sub 3/I and /sup 11/C-labeled radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Vandewalle, T.; Vandecasteele, C.; Guchteneire, F. de; Meulewaeter, L.; Haver, D. van; Denutte, H.; Goethals, P.; Slegers, G. (Ghent Rijksuniversiteit (Belgium))

    1985-06-01

    An automated system for the production of /sup 11/C-labeled radiopharmaceuticals, using /sup 11/C-CH/sub 3/I as a precursor, has been developed. The whole procedure, including irradiation, production of /sup 11/C-CH/sub 3/I, synthesis of the labeled molecule and isolation of the final product is controlled by a microprocessor. Between 30 and 80 mCi of 5 different radiopharmaceuticals are produced routinely with this system.

  9. Difficulties and aspects to take into account in the production, use and distribution of new radiopharmaceuticals PET; Difficultes et aspects a prendre en compte dans la production, l'utilisation et la distribution des nouveaux radiopharmaceutiques TEP

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, R.; Rayo, J.I.; Serrano, J.; Infante, J.; Luz Dominguez, M.; Garcia, L.; Duran, C. [Hospital Infanta Cristina, Servicio de Medicina Nuclear, Badajoz (Spain)

    2008-10-15

    This article seeks to describe the requirements, legal and technical, for the production, distribution and use of new radiopharmaceuticals PET (other than the {sup 18}F.D.G.), describing the legislative framework in which we find ourselves, the characteristics of a production and types of synthesis and existing modules. A list of susceptible radiopharmaceuticals is presented that are being currently used in nuclear medicine by specifying the real possibilities of their production and use and which are the difficulties we face.

  10. 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.

  11. Radiation risk in pediatric patients: the need for criteria using radiopharmaceuticals activities;Risco radiologico em pacientes pediatricos: a necessidade de criterios para o uso de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Simas, Felipe [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Fisica; Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Servico de Monitoracao Individual Interna; Velasques, Silvia M. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Servico de Monitoracao Individual Interna

    2009-07-01

    The administration of radionuclides to children for diagnostic procedures should be carried out only if there is a strong clinical indication. The amount of activity administered may be reduced according to body weight, body surface area or other appropriate criteria. In Brazil, activities used for pediatric patients were evaluated (2003-2005) in sixteen selected public and private institutions in Northeast, Southeast and South geographical regions. The present work presents radiopharmaceuticals activities used in Brazil compared with international surveys performed in USA in 2005 and in the European Union in 2007. The activities per patient weight and minimum and maximum activities used per Brazilian installations were compared with those used in USA installations. Per patients, it was calculated the ideal minimum administered activity for each type of radiopharmaceutical by body weight according the Pediatric Dosage Card (PDC) criteria. It was not possible to compare activities for all radiopharmaceuticals used in Brazil because some are not more used outside, e.g. {sup 131}I-NaI, which is replaced by {sup 123}I-NaI for thyroid imaging. The discrepancy between activities used in Brazil compared with those used in USA and Europe may be attributed to the heterogeneity of Brazilian imaging equipment and lack for specific children protocols. The disadvantages for using fractions of adult activities are: necessity of minimum statistical counting for assurance of image quality and dependence upon equipment calibration. It was concluded that is necessary to establish standard criteria for radiopharmaceuticals activities applied to pediatric patients in Brazil and the risks due to additional activities should be estimated individually. (author)

  12. 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)

  13. Effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Jia-Lun Zhu; Zhi-Yong Deng; Chuan-Zhou Yang

    2016-01-01

    Objective:To find the effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis.Methods: A total of 102 lung cancer patients with bone metastases were included in the study and randomly divided into observation group and control group (n=51) according to different treatment they received. Control group received zoledronic acid injection therapy alone, observation group received zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy, and then differences in the growth of lung cancer bone metastasis, bone metabolism, tumor markers and alkaline phosphatase, pain score and pain-related mediator levels,etc. were compared between two groups.Results: Number of metastases of observation group after treatment was less than that of control group, and serum bone metabolism indexes OPG, BSP, TRACP-5b, ICTP and BAP levels, serum tumor markers CYFRA21-1, CEA, NSE, CA125 and BALP levels as well as serum pain-related mediators PGE2, ET-1 and TNF-α levels were lower than those of control group (P<0.05).Conclusions:Zoledronic acid injection combined with radiopharmaceutical89SrCI2 therapy can contain the growth of lung cancer bone metastasis, optimize bone metabolism state while alleviate patients’ perception of pain.

  14. 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.

  15. 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.

  16. Laser stimulation of the acupoint ‘Zusanli’ (ST.36) on the radiopharmaceutical biodistribution in Wistar rats

    Indian Academy of Sciences (India)

    Eric Hff Frederico; Ailton A Santos; Danubia C Sa-Caputo; Rosane F Neves; Carlos As Guimaraes; Shyang Chang; Mario Bernardo-Filho

    2016-03-01

    Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the ‘Zusanli’ acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na 99mTcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm2) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na 99mTcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

  17. New pathways to medicare coverage for innovative PET radiopharmaceuticals: report of a medical imaging & technology alliance (MITA) workshop.

    Science.gov (United States)

    Hillman, Bruce J; Frank, Richard A; Rodriguez, Gail M

    2012-02-01

    PET and PET/CT have revolutionized the diagnosis, staging, and monitoring of treatment effect or recurrence for a wide range of cancers and shown promise for improving health outcomes for patients with cardiovascular and central nervous system diseases. However, this technology is challenged by insurance coverage policies that hinder patients' access to PET and discourage technologic innovation. Recently, the Medical Imaging & Technology Alliance (MITA), a Washington-based industry association, convened a workshop to consider new pathways for making decisions on Medicare coverage of new PET radiopharmaceuticals and imaging procedures that are currently subject to a national noncoverage decision, or "exclusionary rule." Stakeholders from the government, medical professional societies, academia, patient groups, and industry gathered to brainstorm alternatives to the national noncoverage decision and evaluate their potential to improve access and enhance innovation. Ultimately, MITA, on behalf of the PET community, expects to use the outcomes of the workshop to propose that the Centers for Medicare and Medicaid Services reconsider this current national noncoverage decision for PET and adopt a new framework for coverage.

  18. Comparison of four technetium-99m radiopharmaceuticals for detection and localization of gastrointestinal bleeding in a sheep model

    Energy Technology Data Exchange (ETDEWEB)

    Owunwanne, A.; Al-Wafai, I.; Vallgren, S.; Sadek, S.; Abdel-Dayem, H.M.; Yacoub, T.

    1988-01-01

    Four Tc-99 radiopharmaceuticals, Tc-99m sulphur colloid, Tc-99m red blood cells (RBCs), Tc-99m mercaptoacetyltriglycine (MAG3), and Tc-99m DTPA, were studied in an experimental animal model for detection and localization of gastrointestinal (GI) bleeding site in both the upper and lower abdomen. With Tc-99m sulphur colloid and Tc-99m RBCs, it was possible to detect and localize the GI bleeding site in the lower abdomen. With Tc-99m MAG3, it was possible to visualize the bleeding site in both the upper and lower abdomen. However, Tc-99m MAG3 is partially excreted by the liver into the bile, hence it will be difficult to use Tc-99m MAG3 to localize the GI bleeding site in the lower abdomen. With Tc-99m DTPA, it was possible to detect and localize the GI bleeding site simultaneously in both upper and lower abdomen. The overall background radioactivity was reduced considerably by diuresis with frusemide and catheterization of the urinary bladder.

  19. Molecular modeling in the development of metal radiopharmaceuticals. Final progress report, July 15, 1989--July 14, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Green, M.A.

    1993-10-01

    We began this project with a compilation of a structural library to serve as a data base containing descriptions of the molecular features of metal-labeled radiopharmaceuticals known to efficiently cross the blood-brain barrier. Such a data base is needed in order to identify structural features (size, shape, molecular surface areas and volumes) that are critical in allowing blood-brain barrier penetration. Nine metal complexes have been added to this structural library. We have completed a detailed comparison of four molecular mechanics computer programs QUANTA, SYBYL, BOYD, and MM2DREW to assess their applicability to modeling the structures of low molecular weight metal complexes. We tested the ability of each program to reproduce the crystallographic structures of 38 complexes between nickel(II) and saturated N-donor ligands. The programs were evaluated in terns of their ability to reproduce structural features such as bond lengths, bond angles, and torsion angles. Recently, we investigated the synthesis and characterization of lipophilic cationic gallium complexes with hexadentate bis(salicylaldimine) ligands. This work identified the first gallium-68 radiopharrnaceuticals that can be injected intravenously and that subsequently exhibit significant myocardial uptake followed by prolonged myocardial retention of {sup 68}Ga radioactivity. Tracers of this type remain under investigation as agents for evaluation of myocardial perfusion with positron emission tomography.

  20. 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.

  1. 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)

  2. Technetium-99m d,l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Neirinckx, R.D.; Canning, L.R.; Piper, I.M.; Nowotnik, D.P.; Pickett, R.D.; Holmes, R.A.; Volkert, W.A.; Forster, A.M.; Weisner, P.S.; Marriott, J.A.

    1987-02-01

    Following investigation of a large number of new ligands based upon propylene amine oxime (PnAO) the d,l-diastereoisomer of hexamethyl propyleneamine oxime (HM-PAO) was selected as the preferred ligand for 99mTc as a tracer for cerebral perfusion imaging. The neutral, lipophilic 99mTc complex of d,l-HM-PAO was formed in high yield by stannous reduction of 99Mo/99mTc generator eluate using a kit formulation of the ligand. Two minutes following i.v. administration of this complex in rats, 2.25% of the injected dose appears in the brain. Little washout of the tracer is observed up to 24 hr postinjection. By qualitative autoradiographic comparison with iodoantipyrine this new radiopharmaceutical displays blood flow dependent brain uptake with little redistribution of the tracer over time. The lipophilic 99mTc complex converts slowly in vitro to a secondary complex. This conversion process may account for the ability of (99mTc)d,l-HM-PAO to be retained within the brain without redistribution.

  3. 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.

  4. A radiopharmaceutical for imaging areas of lymphocytic infiltration: [sup 123]I-interleukin-2. Labelling procedure and animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Signore, A.; Chianelli, M.; Toscano, A.; Monetini, L.; Ronga, G.; Pozzilli, P.; Negri, M. (Policlinico Umberto, Rome (Italy). Clinica Medica 2); Nimmon, C.C.; Britton, K.E. (Saint Bartholomew' s Hospital, London (United Kingdom). Dept. of Nuclear Medicine)

    1992-10-01

    The labelling of interleukin-2 (IL-2) with [sup 123]I and its in vivo application for imaging chronic pathological lymphocytic infiltrations are described. The lactoperoxidase/glucoseoxidase technique was the labelling method of choice leading to immunoreactive IL-2 with high specific activity. Labelled IL-2 was injected in diabetes-prone non-obese diabetic (NOD) mice with pancreatic lymphocytic infiltration. As control animals, Balb/c mice were used. As specificity control, monoclonal antibodies AMT13 and UCHT1, bovine serum albumin and [alpha]-lactalbumin were radioiodinated and injected in mice. Eighteen NOD mice and four control Balb/c mice were used for gamma camera imaging experiments. Fifty-four NOD and 20 Balb/c mice were used for time course single organ counting and autoradiography. Gamma camera images showed that radioactivity accumulated in the pancreatic region from the 10th minute onwards in NOD mice injected with [sup 123]I-IL-2 but not in Balb/c mice, or in NOD mice injected with control radiopharmaceuticals. These findings were confirmed by counting the radioactivity present in single organs. Autoradiography of NOD pancreas, after injection of labelled IL-2, showed that radioactivity was specifically associated with infiltrating lymphocytes. In conclusion, this technique is highly specific and easy to perform and we suggest its application in humans for in vivo detection of areas of lymphocytic infiltration. (Author).

  5. 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.

  6. {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.

  7. 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)

  8. 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)

  9. A new monoclonal antibody radiopharmaceutical for radioimmunoscintigraphy of breast cancer: direct labeling of antibody and its quality control

    Directory of Open Access Journals (Sweden)

    Mojtaba Salouti

    2006-03-01

    Full Text Available Radioimmunoscintigraphy (RIS has found widespread clinical application in tumor diagnosis. The antibody (Ab PR81 is a new murine anti-MUC1 monoclonal antibody (MAb against human breast carcinoma. In this study a very simple, rapid and efficient method for labeling of this MAb with 99mTc, particularly suitable for development of a ‘kit’is described. The reduction of Ab was performed with 2-mercaptoethanol (2-ME at a molar ratio of 2000:1 (2-ME:MAb and the reduced Ab was labeled with 99mTc via methylene diphosphonate (MDP as a transchelator. The labeling efficiency which was determined by instant thin layer chromatography (ITLC was 94.2%±2.3. Radiocolloides measured by cellulose nitrate electrophoresis were 2.5%±1.7. In vitro stability of the labeled product in human serum which was measured by gel filtration chromatography (FPLC was 70%±5.7 over 24 hr. The integrity of labeled MAb was checked by means of SDS-PAGE and no significant fragmentation was observed. The results of the cell-binding studies showed that both labeled and unlabeled PR81 were able to compete for binding to MCF 7 cells. Biodistribution studies were performed in normal BALB/c mice at 4 and 24 hrs post-injection and no important accumulation was observed in vital organs. These results show that the new radiopharmaceutical may be considered as a promising candidate for imaging of breast cancer.

  10. 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.

  11. Control flow of radiopharmaceuticals in nuclear medicine by means of an E-service; Control flujo de radiofarmacos en medicine nuclear por medio de un E-servicio

    Energy Technology Data Exchange (ETDEWEB)

    Nunez Martin, L.; Gonzalez de Mingo, M. A.; Fragua Redondo, J. A.; Martinez Ortega, J.; Gutierrez Camunas, S.; Redondo Miguel, A. B.

    2013-07-01

    The almost generalized use of single-dose Nuclear Medicine for performing diagnostic tests or treatments, and the consequent complexity that accompanies its management, has resulted in the need to control the flow of material radioisotopic tools. An e-service is designed to manage the flow of radiopharmaceuticals and control its use and spending. This control does not only affect the efficiency in the use and cost of material, but in the radioactive waste associated with the non-use and waste reduction and a more effective organization of the Department. (Author)

  12. 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)

  13. Study of the influence of the protective covering from contamination on the radiopharmaceutical bottle in measurement of activity; Estudo da influencia do involucro protetor de contaminacao no frasco de radiofarmacos na medicao da atividade

    Energy Technology Data Exchange (ETDEWEB)

    Kuahara, L.T.; Correa, E.L.; Potiens, M.P.A, E-mail: lilian547@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2014-07-01

    This study aims to determine the influence of the use of a plastic covering on the bottle used to supply radiopharmaceuticals to analyze the feasibility of its use at the time of manufacture, in order to avoid contamination in the activity meter well chamber. For that were held several measured with liquid {sup 137}Cs source with and without this envelope and the activity meters of the calibration laboratory. Tests showed a small variation in the percentage of measures with the plastic covering, value considerably low, which will not cause injury in providing radiopharmaceuticals for the Service Nuclear Medicine.

  14. Synthesis of [1-{sup 11}C]octanoic acid, [{sup 11}C]raclopride and [{sup 11}C]nicergoline with a general-purpose automated synthesis apparatus of {sup 11}C-labeled radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Yajima, Kazuyosi; Kawashima, Hidefumi; Cui, Ying-she; Hashimoto, Naoto; Miyake, Yoshihiro [National Cardiovascular Center, Suita, Osaka (Japan)

    1997-06-01

    We have developed a general-purpose automated synthesis apparatus of {sup 11}C-labeled radiopharmaceuticals for PET, which can be adopted to both one-pot and two-or-more-pot reactions. The features of the apparatus were shown in the successful preparation of [(1-{sup 11})C]octanoic acid in a one-pot reaction and [{sup 11}C]raclopride and [{sup 11}C]nicergoline in two-pot reactions, the latter being a novel radiopharmaceutical. (author).

  15. 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)

  16. 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)

  17. 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.

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

    Science.gov (United States)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2011-01-01

    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 (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 (Na⁹⁹mTcO₄)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 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.

  19. 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

  20. 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

  1. 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)

  2. 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)

  3. 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)

  4. Rapid brain scanning radiopharmaceutical

    Science.gov (United States)

    Sargent, III, Thornton W.; Shulgin, Alexander T.; Mathis, Chester A.

    1987-01-01

    A method for detecting the blood flow in animals, particularly in the brain, is provided wherein a detectable amount of a novel radioactive compound of the formula I is administered to one animal: ##STR1## wherein R.sub.1 and R.sub.2 are independently alkyl of 1 to 6 carbon atoms or benzyl; R.sub.3 is alkyl of 1 to 6 carbon atoms, benzyl, cyclopropylalkyl of 4 to 6 carbon atoms, or cyanoalkyl of 2 to 6 carbon atoms; R.sub.4 is hydrogen, benzyl or alkyl of 1 to 6 carbon atoms; with the provisos that R.sub.4 is not isopropyl and when R.sub.4 is methyl, R.sub.3 is not benzyl; and X is a radioactive halogen.

  5. 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...

  6. 中国放射性药物的现状与展望%Current Status and Prospects of Radiopharmaceuticals in China

    Institute of Scientific and Technical Information of China (English)

    贾红梅; 刘伯里

    2011-01-01

    放射性药物不仅可以作为有效的诊断和治疗手段,而且结合单光子断层扫描仪(SPECT)或正电子断层扫描仪(PET),还可以在分子水平上直接研究它们在正常人体(活体)内的功能和代谢过程,实现人体内生理和病理过程的快速、无损和实时成像,为真正意义上的早诊断、早治疗提供新方法和新手段,为预防医学、转化医学、个性化医学的实现提供可能的途径.本文概述了体内放射性药物的最新进展,分析了我国放射性药物的研究现状,提出大力加强医用放射性核素的研制、加强基础放射性药物化学研究、系统开展受体分子显像剂的研究以及开展多模式多功能复合分子探针的研究等建议.%Radiopharmaceuticals could not only serve as effective diagnostic and therapeutic tools in human diseases, but also allow the assessment of metabolism and functional processes by providing quick, non-invasive and real-time visualization of physiological and pathological processes in the living humans at the molecular level together with PET (positron e-mission tomography) and SPECT (single photon emission computed tomography) imaging modalities. They could provide new methods and new approaches of truly early diagnosis and therapy and possible pathways for the preventative medicine, translational medicine and personalized medicine. The present review provides an overview of current status of in vivo radiopharmaceuticals in China. Moreover, some prospects of research and development of radiopharmaceuticals in the near future was discussed. The addressed future trends include the following aspects. (1) Production of medical radioisotopes including 99Mo, 131I, 188/186Re and 123I. (2) Investigation on the basic radiopharmaceutical chemistry. (3) Development of receptor-based imaging agents. (4) Development of multi-modality imaging probes.

  7. 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

  8. Determination of {sup 125}I impurities in [{sup 123}I]labelled radiopharmaceuticals, by liquid scintillation counting: sensitivity of the method

    Energy Technology Data Exchange (ETDEWEB)

    Bonardi, M.L. E-mail: mauro.bonardi@mi.infn.itmauro.bonari@mi.infn.it; Birattari, C.; Groppi, F.; Gini, L.; Mainardi, C.H.S.; Menapace, E

    2004-01-01

    Iodine-125 is a radioisotopic impurity 'always' present in iodine-123, produced by nuclear reactions induced either on natural or 'highly' enriched targets. Liquid scintillation counting is a very sensitive tool to determine low level impurities of both low energy electrons and photons in aqueous and organic solutions of radiopharmaceutical compounds. With this technique it was possible to determine, on commercial samples, that the content of {sup 125}I was of the order of not less than 0.1% for {sup 123}I produced via {sup 127}I(p,5n) reactions and not less than 0.01% for {sup 123}I produced via 'highly' enriched {sup 124}Xe(p,X) nuclear reactions.

  9. 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)

  10. 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

  11. 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)

  12. 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.

  13. 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

  14. 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)

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA

    Science.gov (United States)

    Pereira, Edgar; Do Quental, Letícia; Palma, Elisa; Oliveira, Maria Cristina; Mendes, Filipa; Raposinho, Paula; Correia, Isabel; Lavrado, João; di Maria, Salvatore; Belchior, Ana; Vaz, Pedro; Santos, Isabel; Paulo, António

    2017-02-01

    A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners.

  20. 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.

  1. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Matthias Eder

    2014-06-01

    Full Text Available The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx-HBED-CC ([68Ga]Ga-PSMA-HBED-CC represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective 68Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [68Ga]Ga-PSMA-HBED-CC.

  2. 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)

  3. 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)

  4. 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

  5. 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

  6. 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.

  7. Synthesis, quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the Center for Development of Nuclear Technology - CDTN

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina Bicalho; Soares, Marcella Araugio; Valente, Eduardo Sarmento; Waquil, Samira Soares; Santos, Raquel Gouvea dos; Silva, Juliana Batista da, E-mail: silvajb@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Serv. de Aplicacao das Radiacoes na Saude; Ferreira, Andrea Vidal [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Serv. de Reator e Irradiacoes

    2010-07-15

    {sup 18}F-Sodium fluoride (Na{sup 18}F) is a radiopharmaceutical used for diagnosis in nuclear medicine by positron emission tomography (PET) imaging. Bone scintigraphy is normally performed using {sup 99m}Tc- MDP. However, {sup 18}F 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 Na{sup 18}F injectable solution with the physical-chemical, microbiological and biological characteristics recommended in the U.S. Pharmacopeia. Na{sup 18}F 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 < 5.0 EU.mL{sup -1} and no microbial contaminants. The biodistribution of Na{sup 18}F was similar to that described in the literature, with a clearance of 0.19 mL.min{sup -1} and distribution volume of 18.76 mL. The highest bone concentration (5.0 {+-} 0.5 %ID.g{sup -1}) was observed 20 minutes after injection. Na{sup 18}F produced at the UPPR presented all the quality assurance requirements of the U.S. Pharmacopeia and can be safely used for clinical bone imaging. (author)

  8. Radiolabeling of new generation magnetic poly(HEMA-MAPA) nanoparticles with (131) I and preliminary investigation of its radiopharmaceutical potential using albino Wistar rats.

    Science.gov (United States)

    Avcıbaşı, Uğur; Demiroğlu, Hasan; Ediz, Melis; Akalın, Hilmi Arkut; Özçalışkan, Emir; Şenay, Hilal; Türkcan, Ceren; Özcan, Yeşim; Akgöl, Sinan; Avcıbaşı, Nesibe

    2013-12-01

    In this study, N-methacryloyl-l-phenylalanine (MAPA) containing poly(2-hydroxyethylmethacrylate) (HEMA)-based magnetic poly(HEMA-MAPA) nanobeads [mag-poly(HEMA-MAPA)] were radiolabeled with (131) I [(131) I-mag-poly(HEMA-MAPA)], and the radiopharmaceutical potential of (131) I-mag-poly(HEMA-MAPA) was investigated. Quality control studies were carried out by radiochromatographic method to be sure that (131) I binded to mag-poly(HEMA-MAPA) efficiently. In this sense, binding yield of (131) I-mag-poly(HEMA-MAPA) was found to be about 95-100%. In addition to this, optimum radiodination conditions for (131) I-mag-poly(HEMA-MAPA) were determined by thin-layer radiochromatography studies. In addition to thin-layer radiochromatography studies, lipophilicity (partition coefficient) and stability studies for (131) I-mag-poly(HEMA-MAPA) were realized. It was determined that lipophilicities of mag-poly(HEMA-MAPA) and (131) I-mag-poly(HEMA-MAPA) were 0.12 ± 0.01 and 1.79 ± 0.76 according to ACD/logP algorithm program, respectively. Stability of the radiolabeled compound was investigated in time intervals given as 0, 30, 60, 180, and 1440 min. It was found that (131) I-mag-poly(HEMA-MAPA) existed as a stable complex in rat serum within 60 min. After that, biodistribution and scintigraphy studies were carried out by using albino Wistar rats. It was determined that the most important (131) I activity uptake was observed in the breast, the ovary, and the pancreas. Scintigraphy studies well supported biodistribution results.

  9. 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)

  10. 99mTc complex conjugated to insulin: CNS radio-pharmaceuticals design based on principles of blood-brain barrier transport vector

    Institute of Scientific and Technical Information of China (English)

    LIU Fei; FAN Caiyun; ZHANG Jinming; WANG Wushang; LIU Boli

    2005-01-01

    Hydrophilic 99mTc-EC and nonlipophilic 99mTc- MAMA′-BA complexes, owing to the existing of intact blood-brain barrier (BBB) in vivo, cannot cross from blood to brain. Previous studies showed that insulin is selectively transported by receptor-mediated transcytosis through the brain capillary endothelial wall that makes up the BBB. In this paper, based on the characteristic of the insulin receptor enriched in brain capillary, the complexes of hydrophilic 99mTc-EC and nonlipophilic 99mTc-MAMA′-BA are conjugated to insulin respectively. After purification, the radiochemical purity of 99mTc-EC-insulin and 99mTc-MAMA′- BA-insulin was > 90% and the stability in vitro was good. Expectation for the special formulation can be internalized and endocytosed into the capillary membrane by the vector-mediated brain delivery system, and transported 99mTc-labeled conjugate through the BBB in vivo, thus enhancing brain uptake in mice. The biodistribution results of 99mTc-EC-insulin and 99mTc-MAMA′-BA-insulin in mice indicated that the brain uptake was higher than 99mTc-EC and 99mTc-MAMA′-BA to some extent. The ratios of brain uptake of 99mTc-EC-insulin to 99mTc-EC, 99mTc-MAMA′-BA-insulin to 99mTc-MAMA′-BA were 4―6 at 2 and 3 h post-injection respectively. In conclusion, the given results have illustrated a new way of brain uptake enhancing for nonlipophilic like complexes that have BBB delivery problems. It has a potential value for the ongoing development of 99mTc-labeled radiopharmaceuticals for CNS receptors imaging.

  11. 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

  12. 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)

  13. 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

  14. 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

  15. 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)

  16. 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)

  17. Body parts

    Science.gov (United States)

    Ayiter, Elif

    2010-01-01

    In this project, the artist wishes to examine corporeality in the virtual realm, through the usage of the (non)-physical body of the avatar. An art installation created in the virtual world of Second Life, which is meant to be accessed with site specific avatars, will provide the creative platform whereby this investigation is undertaken. Thus, "body parts" seeks to challenge the residents of virtual environments into connecting with the virtual manifestations, i.e., avatars of others in an emotionally expressive/intimate manner.

  18. 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...... houses with measurements of heat, power and hot water consumption every 15th minute during one year. Three scenarios are analyzed ranging from heat following only (grid compensation for electricity) to heat and power following with net export of electricity during high and peak load hours. Average...

  19. 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.

  20. 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)

  1. Review of Domestic F-18 Multifunctional Module and Synthesis Positron Radiopharmaceuticals%国产氟-18多功能模块及合成正电子放射性药物概述

    Institute of Scientific and Technical Information of China (English)

    张帆; 于璟

    2016-01-01

    The ifeld of radiochemistry is moving towards exclusive use of automated synthesis modules for production of most clinical radiopharmaceutical doses. Such a move comes with many advantages, but also presents radiochemists with many chalenges. This review introduces the characteristic of the PET-MF-2V-IT-I synthesis module, and use it to automate synthetize a series of radiopharmaceutical with the method of single tube synthesis, double tube synthesis, click chemistry synthesis and combined with 1C-CH3I synthesis module, in order to meet the requirements of clinical and scientiifc research .%正电子放射性药品大多采用自动化模块合成以适应临床需要,这种全自动化模块的生产模式有其自身优势,但同时也带来了很大的挑战。本文介绍了国产PET-MF-2V-IT-I型氟-18多功能模块的特点,并运用该模块进行单反应管合成、双反应管合成、点击化学合成、联合11C碘代甲烷模块合成多种放射性药物,以满足临床及科研的需求。

  2. 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

  3. Synthesis, analysis, purification and biodistribution in an animal model of radiopharmaceutical {sup 177}Lu{sup 3+} -dotatato for diagnostic and therapeutic use in neuroendocrine tumors; Sintese, analise, purificacao e biodistribuicao em modelo animal do radiofarmaco {sup 177}Lu{sup 3+} -dotatato para uso diagnostico e terapeutico em tumores neuroendocrinos

    Energy Technology Data Exchange (ETDEWEB)

    Caldeira Filho, Jose de Souza

    2009-07-01

    The aim of this work was to propose rationalization in the synthesis, analysis and purification of radiopharmaceutical {sup 177} Lu{sup 3+} - DOTATATO for diagnostic and therapeutic use in neuroendocrine tumors, as well as for evaluation g biodistribution of this radiopharmaceutical an animal-mode. The complexation reaction for the synthesis of radiopharmaceutical was carried out in ammonium acetate buffer 0.5 M, p H 7.0, for 30 minutes at 95 deg C. The radiochemical purity was > 95%, according to analysis by chromatography in ITLC-SG, when using the sodium citrate buffer 0,1 M, p H 5.0, as the mobile phase. The molar-limit ratio {sup 177}Lu{sup 3+}:DOTATATO, in ammonium acetate buffer 0.5 M, p H 7.0, for 30 minutes at 95 deg C, was dependent on the specific activity and origin of the radioisotope, this being 1:3.5 (370 MBq : 26{mu}g) for that from the Oak Ridge National Laboratory /USA, and 1:16 (370 MBq: 11.8 {mu}g) for that from Nuclear Analytical and Medical Services/Holland, when considering a decay of five days from the production date of te radioisotopes. This rationalization in the synthesis of radiopharmaceutical {sup 177}Lu{sup 3+} - DOTATATO permits high economy in production costs. Chemical studies on the synthesis of radiopharmaceuticals also placed in evidence the interference of {sup 177}Hf{sup 4+}, the decay product of {sup 177}Lu{sup 3=}, as the {sup 177} Lu{sup 3=} competitor for DOTATATO. Radiopharmaceutical preparation proved to be stable during 24 hours, at an activity rate of 2775 MBq, with the addition of 0.6 mg/mL of gentisic acid and when kept in dry ice. In biodistribution studies on Swiss and Nuce mice, the specificity of radiopharmaceutical for somatostatin positive-receptor tissues, such as the pancreas, stomach, lungs, adrenal glands, kidneys and the cell tumor AR42J was demonstrated. (author)

  4. 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

  5. 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.

  6. 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)

  7. 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.

  8. [Bone metastases treated with radiopharmaceuticals].

    Science.gov (United States)

    Giammarile, Francesco

    2013-11-01

    The administration of a radionuclide in unsealed source whose radiation will destroy cells that have selectively accumulated product is called radiometabolic therapy. The management of bone pain is a major problem, particularly in cases of breast or prostate where the presence of metastases can remain compatible with long-term survival of cancer patients. In this context, the radiometabolic therapy reduces the pain secondary to bone metastases, in association or not with analgesics. This technique is rarely prescribed as first-line. It can also be combined with external beam radiotherapy or chemotherapy, if clinical conditions permit (due to the increased risk of hematologic toxicity). In this setting, the currently used substances are Metastron® and Quadramet®. Recently, a new product, radium chloride (or Alpharadin®) has shown efficacy in bone metastases from prostate cancer, particularly in terms of bone pain palliation, but also of increased overall survival. In addition, this product has virtually no hematologic toxicity.

  9. Small Molecule PET-Radiopharmaceuticals

    NARCIS (Netherlands)

    Elsinga, Philip H.; Dierckx, Rudi A. J. O.

    2014-01-01

    This review describes several aspects required for the development of small molecule PET-tracers. Design and selection criteria are important to consider before starting to develop novel PET-tracers. Principles and latest trends in C-11 and F-18-radiochemistry are summarized. In addition an update o

  10. Standardization of administered activities in pediatric nuclear medicine: a report of the first nuclear medicine global initiative project, part 1-statement of the issue and a review of available resources.

    Science.gov (United States)

    Fahey, Frederic H; Bom, Henry Hee-Seong; 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

    2015-04-01

    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 were 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. This article presents part 1 of the final report of this initial project of the NMGI. It provides a review of the value of pediatric nuclear medicine, the current understanding of the carcinogenic risk of radiation as it pertains to the administration of radiopharmaceuticals in children, and the application of dosimetric models in children. A listing of pertinent educational and reference resources available in print and online is also provided. The forthcoming part 2 report will discuss current standards for administered activities in children and adolescents that have been developed by various organizations and an evaluation of the current practice of pediatric nuclear medicine specifically with regard to administered activities as determined by an international survey of nuclear medicine clinics and centers. Lastly, the part 2 report will recommend a path forward toward global standardization of the administration of radiopharmaceuticals in children.

  11. 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

  12. 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

  13. 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.

  14. A simple method for preparation of pure (68) Ga-acetate precursor for formulation of radiopharmaceuticals: Physicochemical characteristics of the (68) Ga eluate of the SnO2 based-(68) Ge/(68) Ga column generator.

    Science.gov (United States)

    Chattopadhyay, Sankha; Alam, Md Neyar; Smita, Madhu; Kumar, Umesh; Das, Sujata Saha; Barua, Luna

    2017-01-01

    Gallium-68 radioisotope is an excellent source in clinical positron emission tomography application due to its ease of availability from germanium-68 ((68) Ge)/gallium-68 ((68) Ga) generator having a shelf life of 1 year. In this paper, a modified method for purification of the primary eluate of (68) Ge-(68) Ga generator by using a small cation exchange resin (Dowex-50) column has been described. The breakthrough of (68) Ge before and after purification of (68) Ga eluate was 0.014% and 0.00027%, respectively. The average recovery yield of (68) Ga after purification was 84% ± 8.6% (SD, n = 335). The results of the physiochemical studies confirmed that the (68) Ga-acetate obtained is suitable for labeling of radiopharmaceuticals.

  15. 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.

  16. 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)

  17. 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

  18. 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)

  19. 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)

  20. 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

  1. 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)

  2. Clinical applications of single photon emission tomography in neuromedicine. Part 1. Neuro-oncology, epilepsy, movement disorders, cerebrovascular disease; Klinische Anwendungen der Single-Photon-Emissionstomographie in der Neuromedizin. Teil 1. Neuroonkologie, Epilepsien, Basalganglienerkrankungen, zerebrovaskulaere Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Bartenstein, P.; Gruenwald, F.; Kuwert, T.; Tatsch, K.; Sabri, O.; Benkert, O.; Fahlbusch, R.; Gruender, G.; Herzholz, K.; Weiller, C. [Universitaetsklinikum Mainz (Germany). Klinik und Poliklinik fuer Nuklearmedizinn

    2000-11-01

    Single photon emission tomography is, because of its availability and the relatively low costs, the functional imaging modality currently most widely used for clinical applications in the brain. Beside the application of radiopharmaceuticals for the assessment of regional cerebral blood flow there is an increasing clinical use of more selective SPECT-radiopharmaceuticals, like amino acid analogs or receptor ligands. This article gives in its first part a critical review of the clinical applications of SPECT in neuro-oncology, epilepsy, basal ganglia disorders and cerebrovascular disease. (orig.) [German] Die Single-Photon-Emissionstomographie ist wegen ihrer allgemeinen Verfuegbarkeit und der relativen Kostenguenstigkeit weiterhin das funktionell bildgebende Verfahren mit der groessten klinischen Bedeutung fuer die Diagnostik von Erkrankungen des zentralen Nervensystems. Neben Radiopharmaka, die den regionalen zerebralen Blutfluss erfassen, werden zunehmend selektivere Pharmaka fuer klinische Fragestellungen eingesetzt, wie Aminosaeurederivate oder Rezeptorliganden. Die Arbeit vermittelt in ihrem ersten Teil eine kritisch wertende Uebersicht ueber die klinischen Anwendungsmoeglichkeiten von SPECT-Untersuchungen bei Fragestellungen aus der Neuroonkologie, der Epilepsiediagnostik, bei Basalganglienerkrankungen und zerebrovaskulaeren Erkrankungen. (orig.)

  3. 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

  4. 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

  5. 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)

  6. 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...

  7. 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...

  8. 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......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...

  9. GC法测定正电子类放射性药物制剂中有机溶剂残留量%GC Determination of Residual Solvents in PET Radiopharmaceutical Injection

    Institute of Scientific and Technical Information of China (English)

    武仙英; 贾娟娟; 乔洪文; 邓艾芳; 乔晋萍; 朱霖; 钟建国

    2014-01-01

    目的:建立GC法测定正电子类放射性药物注射剂中有机溶剂残留量。方法色谱柱为DB-FFAP石英毛细管柱(30 m ×0.32 mm,0.5μm),FID检测器,载气为氮气。进样口温度200℃;检测器温度250℃;程序升温:初始温度40℃,保持5 min,以40℃·min-1升温至200℃,保持5 min。手动进样,不分流模式。结果乙腈在0.008%~0.080%(g·g-1)范围内线性关系良好( r =0.9981),[18F]AV-133和[18F]AV-45制剂的平均加样回收率分别为94.26%和93.74%,RSD为3.27%和5.23%( n =9);二甲亚砜在0.10%~1.00%(g·g-1)范围内线性关系良好( r =0.9964),[18F]AV-133和[18F]AV-45制剂的平均加样回收率分别为96.10%和100.75%,RSD为5.17%和6.52%( n =9)。结论该法简单、灵敏、准确,重复性好,适用于[18 F]AV-133和[18 F]AV-45制剂有机溶剂残留量的检测。%Objective To establish a method of GC for the determination of residual organic solvents in PET ra-diopharmaceutical injection. Methods The residual solvents in PET radiopharmaceutical injection were separated by DB-FFAP capillary column(30 m × 0. 32 mm,0. 5 μm)and analyzed with an FID detector. The carried gas was nitrogen. The injector and detector temperatures were controlled at 200 ℃ and 250 ℃,respectively. The temperature was pro-grammed as follows:maintained at 40℃ for 5 min,raised to 200℃ at the rate of 40℃·min-1 ,and maintained again for 5 min. Hand injection was used in a splitless model. Results The linear range of acetonitrile and dimethylsulfoxide was 0. 008% -0. 080%(g·g-1)( r =0. 998)and 0. 10% -1. 00%(g·g-1)( r =0. 9964),respectively. The average recov-ery of acetonitrile was 94. 26%(RSD=3. 27%)and 93. 74%(RSD=5. 23%)for[18F]AV-133 and[18F]AV-45,while that of dimethylsulfoxide was 96. 10%(RSD=5. 17%)and 100. 75%(RSD=6. 52%)for[18F]AV-133 and[18F]AV-45,respectively. Conclusion This method is simple,accurate and sensitive with good

  10. 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.

  11. Testing the radiochemical purity of radiopharmaceuticals: application to {sup 99m}Tc-HMPAO; Controle de la purete radiochimique des radiopharmaceutiques: application au {sup 99m}Tc-HMPAO

    Energy Technology Data Exchange (ETDEWEB)

    Ait Ben Ali, S.; Darsin, D.; Rizzo, N.; Lours, S.; De Beco, V.; Dumont, A.; Goudou-Sinha, C.; Izembart, M.; Jourdain, J.R.; Lemercier, V.; Linsker, S.; Moati, F.; Piketty, M.L.; Schlageter, M.H.; Moretti, J.L. [Groupe de travail `Radiopharmaceutique - Ile de France` (France)

    1997-12-31

    The low stability of {sup 99m}Tc-HMPAO imposes to carry out the quality testing within the 15 minutes following the preparation. This study has the aim of comparing different methods of radiochemical purity determination (RP) of this radiopharmaceutical in order to validate a fast, reproducible, feasible technique, capable of separating the primary lipophilic {sup 99m}Tc-HMPAO (I) of impurities: hydrophilic secondary complex (II), TcO{sub 4}{sup -}, reduced and halyards Tc. The reference technique associating two thin-layer chromatographies (TLC), `C1` and `C2`, has been compared with a TLC `W` technique and with liquid-liquid extraction `E` technique: C1 - stationary phase, ITLC Silica gel/mobile phase, Butanone-2; C2 - stationary phase, ITLC Silica gel/mobile phase, 0.9% NaCl; W - stationary phase, Papier Whatman n{sup o} 1/mobile phase, Ether; E - extraction with ethyls acetate /0.9% NaCl (1/1 v/v). The `C1` chromatography allows isolating the reduced Tc and the complex II, the `C2` chromatography does the same with TcO{sub 4}{sup -} but it requires too long techniques (20 min.). The `W` and `E` techniques are rapid, reproducible and allow to separate the complex I from the other impurities without discrimination. However, as their results depend upon the deposited quantity of sampling, an optimization and standardization of the techniques are necessary. A forth technique by chromatography on Sep-Pak column is to be evaluated

  12. 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)

  13. 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

  14. Part Machinability Evaluation System

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In the early design period, estimation of the part or the whole product machinability is useful to consider the function and process request of the product at the same time so as to globally optimize the design decision. This paper presents a part machinability evaluation system, discusses the general restrictions of part machinability, and realizes the inspection of these restrictions with the relation between tool scan space and part model. During the system development, the expansibility and understandability were considered, and an independent restriction algorithm library and a general function library were set up. Additionally, the system has an interpreter and a knowledge manager.

  15. 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.

  16. Standard biological parts knowledgebase.

    Directory of Open Access Journals (Sweden)

    Michal Galdzicki

    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.

  17. 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....

  18. 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.

  19. 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)

  20. Scientists Create Part-Human, Part-Pig Embryo

    Science.gov (United States)

    ... 163262.html Scientists Create Part-Human, Part-Pig Embryo One goal of this stem cell research is ... have successfully used human stem cells to create embryos that are part-human, part-pig. Scientists said ...

  1. 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

  2. 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...

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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 comparisons, matrix generation, and the composition of proximity measures, are introduced and discussed. In this second part, the authors introduce and thoroughly demonstrate two related matrix comparison techniques the Mantel test and Procrustes analysis, respectively. These techniques can compare...... important. Alternatively, or as a supplement, Procrustes analysis compares the actual ordination results without investigating the underlying proximity measures, by matching two configurations of the same objects in a multidimensional space. An advantage of the Procrustes analysis though, is the graphical...

  8. Derecho Penal. Parte especial

    OpenAIRE

    Ríos Corbacho, José Manuel

    2014-01-01

    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...

  9. Part TRIPOLI TRIMARAN

    Energy Technology Data Exchange (ETDEWEB)

    Baur, A.; Bourdet, L.; Dejonghe, G.; Ermont, G.; Gonnord, J.; Monnier, A.; Nimal, J.C.; Vergnaud, T. (CEA, CEN Saclay, 91 - Gif-sur-Yvette (France))

    1983-05-01

    This article presents the Monte Carlo criticality codes TRIPOLI and TRIMARAN carried out at the Nuclear Studies Center (CEN) at Saclay. A first part deals with the main schemes of criticality studies carried out at Saclay, the generalities about the three-dimensional Monte-Carlo code TRIPOLI, the geometry and the utilization of sources in TRIPOLI. A second part present the cross section processing and the thermalization processing in TRIPOLI. Some criticality calculations with the code TRIPOLI are then presented. Finally, the TRIMARAN code is presented: the main features, the principles of operation, and the qualifications carried out on this code.

  10. 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

  11. Preparation and Preliminary Evaluation of 177Lu-EDTMP

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>The study on 177Lu labeled radiopharmaceuticals for cancer therapy is fast emerging as an important part of nuclear medicine. 177Lu-EDTMP is possible to be an effective radiopharmaceutical for pain

  12. Multiple part feeding

    DEFF Research Database (Denmark)

    Hvilshøj, Mads; Bøgh, Simon; Nielsen, Oluf Skov

    2012-01-01

    " is capable of successfully servicing four part feeders in three production cells using command signals from an Open Process Control (OPC) server. Furthermore, the paper presents future research and development suggestions for AIMM, which contributes to near-term industrial maturation and implementation...

  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.

  14. Peptide Based Radiopharmaceuticals: Specific Construct Approach

    Energy Technology Data Exchange (ETDEWEB)

    Som, P; Rhodes, B A; Sharma, S S

    1997-10-21

    The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures). In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays RGD receptor with higher density. The results have indicated good diagnostic potential for their use in this clinical situation, as an imaging agent to diagnose ischemic renal injury and differentiate from other causes. Very promising results were obtained with newly developed tuftsin related metallopeptides. A number of these peptides displayed high potency (nM range) in imaging infection. Antagonists were successfully used to image experimentally induced abscesses in rodents. One of the antagonists, termed 99mTc-RMT-1, was evaluated in rabbits and dogs for its applicability as infection/inflammation imaging agent. Both in dog and rabbit infection/inflammation models 99mTc-RMT-1 could be used for rapid scintigraphic diagnosis. A very high and rapid uptake was observed in both soft tissue and bone infection providing a good target to background contrast. The agent also allowed distinction between bone fracture and osteomyelitis. All these results warrant human clinical trials with 99mTc-RMT-1 which may help replace hazardous ex-vivo WBC labeling procedures that are current clincial modality for imaging infection foci.

  15. {sup 188}Re-Labeled Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jae Min [Seoul National University, Seoul (Korea, Republic of)

    2001-10-01

    The search for an ideal radioisotope for radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays with a short physical half-life of 16.9 hr, {sup 188}Re is an excellent candidate for radiotherapy. Its applications include the irradiation of coronary artery to prevent restenosis, treatment of rheumatoid arthritis, treatment of peritoneal effusion. palliation of metastatic bone pain, and treatment of liver cancer.

  16. 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

  17. Son: Part Two

    Directory of Open Access Journals (Sweden)

    Jennifer Higgie

    2005-03-01

    Full Text Available It is 1842. Two Englishman set out on a Grand Tour of Europe and the Middle East. One is a young, gifted artist; the other a Gentleman. By the time they return to England, the artist has become a devotee of the Egyptian god Osiris. One night, after dining together in a small inn in Cobham, he violently murders his beloved father, believing him to be an imposter. Why? Son is a novel inspired by the life of Richard Dadd, one of the greatest Victorian painters and inmate of Bethlem Hospital - more commonly known as Bedlam. Part one of Son was published in PORTAL vol. 1, no. 2, in July 2004. This is the second and concluding part of the novel.

  18. 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)

  19. Exposure of the surgery room during procedures for the per operative detection after administration to the patient of a radiopharmaceutical: preliminary results; Exposition du personnel de bloc operatoire lors des procedures de detection peroperatoire apres administration au patient d'un radiopharmecautique: resultats preliminaires

    Energy Technology Data Exchange (ETDEWEB)

    Ricard, M.; Lamon, A.; Aubert, B. [Institut Gustave Roussy, 94 - Villejuif (France)

    1999-07-01

    The per operative detection consists in administrating to the patient a radiopharmaceutical that will be localised during a surgical operation with a small detector handled by the surgeon. For the thyroid cancers the measurements have been made for four operations, long of three hours, practiced five days after administration of 4 GBq of iodine 131. The measure gave the following results: (right handed surgeon) right hand extremity 40 mSv, left hand 70 mSv, eyes 13 mSv and thyroid 15 mSv. In the case of injection of 40 MBq of indium 111, the dosemeters wore during respectively eight and five hours, the surgeon exposure was 30 mSv and his assistant exposure, situated a little further, was 5 mSv. (N.C.)

  20. 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.

  1. 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

  2. R806 (part 1)

    CERN Multimedia

    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.

  3. Use of HPLC in testing the radiochemical purity of tiatide: comparison with procedure of National Commission for Radiopharmaceuticals; Apport de l`HPLC dans le control de la purete radiochimique du tiatide: comparaison a la procedure de la Commission Nationale des Radiopharmaceutiques

    Energy Technology Data Exchange (ETDEWEB)

    Zimmer, L.; Baulieu, F.; Bugeon, S.; Besnard, J.C.; Guilloteau, D. [CHU Tour (France)

    1997-12-31

    The tiatide (mercapto-acetyl-tri-glycine or MAG-3) is a Tc-labelled radiopharmaceutical currently used in renal functional exploration. However, its labelling does not reach always a pure radiochemical product. The different types of radioactive impurities (hydrophile, lipophile, colloids, reduced pertechnetate) have not all the same renal kinetics and can falsify the scintigraphic quantification of renal clearance, among others by a hepato-biliary fixation. Hence, it is useful for the nuclear physicians to know the radiochemical purity of the labeller injected in order to interpret better the values of renal clearance. We have compared the different available techniques allowing to make evident qualitatively and/or quantitatively the labelling impurities in tiatide. Our aim is to validate, in our working conditions the procedure utilising micro-columns described by National Commission of Radiopharmaceuticals. The thin-layer chromatography (TLC) (plates Merck RP18), currently used, allows separating the tiatide from reduced or hydrolyzed technetium and from free pertechnetate. The hydrophilic or lipophilic impurities are not distinguished among them. Different revealing techniques are available: quantification by the radiochromatography reader (Bioscan, autoradiography on sensible film or by grating plates) and counting by a gamma counter. Secondly, we made use of fractioned elution on chromatographic micro-columns (Sep Pack C18) followed by a gamma counting which allows to distinguish the tiatide and the lipophilic and hydrophilic impurities (without discriminating the reduced pertechnetate and the colloids). Finally, by HPLC (column RP18, isocratic or with gradient elution) allows quantifying the tiatide and the different present impurities: reduced pertechnetate, lipophilic and hydrophilic impurities. In conclusion, the most suited technique of routine analysis of radiochemical purity of tiatide is the fractional elution on micro-column. The TLC seems to be

  4. Happy to be taking part?

    NARCIS (Netherlands)

    M.H. Kwekkeboom; C.M.C. van Weert

    2008-01-01

    Original title: Meedoen en gelukkig zijn. 'Taking part': that is the central plank of Dutch government policy for people with disabilities. But what exactly does 'taking part' mean, and what is needed to ensure that people are willing or able to take part? Does taking part make people happier?. Doe

  5. Son: Part One

    Directory of Open Access Journals (Sweden)

    Jennifer Higgie

    2004-08-01

    Full Text Available It is 1842. Two Englishman set out on a Grand Tour of Europe and the Middle East. One is a young, gifted artist; the other a Gentleman. By the time they return to England, the artist has become a devotee of the Egyptian god Osiris. One night, after dining together in a small inn in Cobham, he violently murders his beloved father, believing him to be an imposter. Why? Son is a novel inspired by the life of Richard Dadd, one of the greatest Victorian painters and inmate of Bethlem Hospital - more commonly known as Bedlam. Part Two of Son will be published in Portal vol. 2, no. 1, January 2005.

  6. 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.

  7. 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...

  8. Visible parts of fractal percolation

    CERN Document Server

    Arhosalo, I; Järvenpää, M; Rams, M; Shmerkin, P

    2009-01-01

    We study dimensional properties of visible parts of fractal percolation in the plane. Provided that the dimension of the fractal percolation is at least 1, we show that, conditioned on non-extinction, almost surely all visible parts from lines are 1-dimensional. Furthermore, almost all of them have positive and finite Hausdorff measure. We also verify analogous results for visible parts from points. These results are motivated by an open problem on the dimensions of visible parts.

  9. 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)

  10. 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

  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. 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

  13. Small Bowel Review - Part I

    OpenAIRE

    ABR Thomson; Wild, G.

    1997-01-01

    Significant advances have been made in the study of the small bowel. Part I of this two-part review of the small bowel examines carbohydrates, including brush border membrane hydrolysis and sugar transport; amino acids, dipeptides, proteins and food allergy, with a focus on glutamine, peptides and macromolecules, and nucleoside...

  14. 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…

  15. The Majorana Parts Tracking Database

    CERN Document Server

    Abgrall, N; Avignone, F T; 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; 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; Zhitnikov, I

    2015-01-01

    The Majorana Demonstrator is an ultra-low background physics experiment searching for the neutrinoless double beta decay of $^{76}$Ge. 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 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 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. Evaluation of new radiopharmaceuticals: synthesis, evaluation, and biodistribution of radiolabelled peptide of VCAM-1 and {alpha}{sub v}{beta}{sub 3}; Evaluation de nouveaux radiopharmaceutiques: synthese, evaluation et biodistribution de nouveaux radiologands peptidiques de VCAM-1 et {alpha}{sub v}{beta}{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Ardisson, V

    2006-07-15

    The new development of nuclear medicine implies the search of new isotopes but also for new vectors specific of functions or metabolic pathways. We investigated new radiopharmaceuticals intended for new diagnostic approaches of two physiopathological mechanisms frequently met in our populations: the atherosclerosis vulnerable plaque and the tumor angio genesis. We studied and optimized the iodine and 99 m-technetium radiolabelling, of a series of peptides in order to allow the in vivo use of these tracers for imaging studies in animals and possibly in humans. The radioiodination, was carried out by electrophilic substitution, and technetium was linked by a tri-carbonyl B.F.C.A. (Isolink). The reaction parameters were defined so that the labelling reactions presents a high radiochemical purity (>95%), and a high specificity activity. The reactions are fast and reproducible. Various physicochemical properties: lipo-solubility, stability of labelling, and pharmacokinetic properties: non specific binding, metabolization and organ biodistribution of peptides in animal model, were studied. These results indicate which peptide may be a suitable candidate for targeting trials. (author)

  18. Gastric emptying scintigraphy: choice by in vitro test, of a new {sup 99m}Tc marker to label solid phase and further analysis with the better radiopharmaceuticals; Radiomarquage au {sup 99m}Tc de la phase solide pour la vidange gastrique: stabilite de 5 radiopharmaceutiques par test in vitro et analyse complementaire sur les 2 plus stables

    Energy Technology Data Exchange (ETDEWEB)

    Blanc, F

    2005-05-15

    The study of gastric emptying by isotopic method occurs regularly in Brest nuclear medicine department. It consists in eating radiolabelled omelette with rhenium sulphide macro-colloid and in drinking radiolabelled water with {sup 111}In-DTPA. The two phases are followed in stomach with gamma-camera. Rhenium sulphide macro-colloid have been taken off the market in january 2004 and no radiopharmaceutical has replaced them. in vitro test permitted us to test solid phase radiolabeling stability with 5 {sup 99m}Tc-vectors used in nuclear medicine. Two of them are suitable for gastric emptying solid phase labelling: the tin fluoride colloids and the sodium phytate but tin fluoride colloids give better labelling stability than sodium phytate. In order to define solid phase marker properties, studies of medium composition by X fluorescence, size by laser granulometry, structure by NMR (nuclear magnetic resonance), TLC (thin layer chromatography) and by centrifugation are done either with the two vectors or only with sodium phytate. Structural properties of tin fluoride colloids are known. Results of this study indicate that phytates can be colloids. Finally, the good gastric emptying solid phase marker must be a colloid with a size of about 200 nm. (author)

  19. High resolution beta imaging systems for quantitative autoradiography. Potential applications in the field of drug or radiopharmaceuticals developments; Autoradiographie quantitative a l'aide des nouveaux systemes d'imagerie Beta a haute resolution: applications a l'evaluation de medicaments ou a la mise au point de radiopharmaceutiques

    Energy Technology Data Exchange (ETDEWEB)

    Barthe, N

    2004-04-01

    Autoradiography, an imaging technique allowing to get the spatial distribution of a radioactive substance in a tissue, is generally obtained by means of films or photographic emulsions. This is a difficult methodology with several limitations: the major one being quantification which is not precise. We have contributed to the development of new high resolution beta imaging systems to replace the photographic emulsion by a direct counting of beta radioactivity. They have similar or improved performances compared to the film. The sensitivity of the detection is specially enhanced, multiplying by a factor of 100 to 500 the rapidity of image acquisition. Linearity of the detectors is improved giving a better dynamic range than the film. So quantification of radioactivity in the tissue sections is obtained with a good reliability. Multi-isotopes imaging is also achieved by using algorithms of separation based on the different characteristics of energies or decaying schemes of the isotopes. Many potential applications can be found in the development of drugs or radiopharmaceuticals. (author)

  20. 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

  1. 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

  2. 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

  3. 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

  4. Medicare Utilization for Part A

    Data.gov (United States)

    U.S. Department of Health & Human Services — This link takes you to the Medicare utilization statistics for Part A (Hospital Insurance HI) which include the Medicare Ranking for all Short-Stay Hospitals by...

  5. World Auto Parts Market Thriving

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ In a global market with increased competition, the global auto industrial chain in some regions of Europe, the U.S. and Japan is transforming into a new relationship between the auto parts producers and complete vehicle producers.

  6. Bringing Ceramic Parts to Earth

    Institute of Scientific and Technical Information of China (English)

    履之

    1995-01-01

    The benefits of using ceramic engine components are well known:They are tougher than metal parts, weigh less, and can withstand hotter operating temperatures.So why aren’t they being used now? High cost.

  7. Medicare Part D Claims Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — This page contains information on Part D claims data for the purposes of research, analysis, reporting, and public health functions. These data will also be used to...

  8. Medicare Part D Program Analysis

    Data.gov (United States)

    U.S. Department of Health & Human Services — This page contains information on Part D program analysis performed by CMS. These reports will also be used to better identify, evaluate and measure the effects of...

  9. Small Bowel Review - Part I

    OpenAIRE

    Thomson, ABR; Wild, G.

    1997-01-01

    Significant advances have been made in the study of the small bowel. Part I of this two-part review of the small bowel examines carbohydrates, including brush border membrane hydrolysis and sugar transport; amino acids, dipeptides, proteins and food allergy, with a focus on glutamine, peptides and macromolecules, and nucleosides, nucleotides and polyamines; salt and water absorption, and diarrhea, including antidiarrheal therapy and oral rehydration treatment; lipids (digestion and absorption...

  10. Identification based on facial parts

    Directory of Open Access Journals (Sweden)

    Stevanov Zorica

    2007-01-01

    Full Text Available Two opposing views dominate face identification literature, one suggesting that the face is processed as a whole and another suggesting analysis based on parts. Our research tried to establish which of these two is the dominant strategy and our results fell in the direction of analysis based on parts. The faces were covered with a mask and the participants were uncovering different parts, one at the time, in an attempt to identify a person. Already at the level of a single facial feature, such as mouth or eye and top of the nose, some observers were capable to establish the identity of a familiar face. Identification is exceptionally successful when a small assembly of facial parts is visible, such as eye, eyebrow and the top of the nose. Some facial parts are not very informative on their own but do enhance recognition when given as a part of such an assembly. Novel finding here is importance of the top of the nose for the face identification. Additionally observers have a preference toward the left side of the face. Typically subjects view the elements in the following order: left eye, left eyebrow, right eye, lips, region between the eyes, right eyebrow, region between the eyebrows, left check, right cheek. When observers are not in a position to see eyes, eyebrows or top of the nose, they go for lips first and then region between the eyebrows, region between the eyes, left check, right cheek and finally chin.

  11. Staircase and fractional part functions

    Science.gov (United States)

    Amram, Meirav; Dagan, Miriam; Ioshpe, Michael; Satianov, Pavel

    2016-10-01

    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 various programming tasks. In this paper, we view the staircase and fractional part functions as a classical example of non-continuous real functions. We introduce some of their basic properties, present some interesting constructions concerning them, and explore some intriguing interpretations of such functions. Throughout the paper, we use these functions in order to explain basic concepts in a first calculus course, such as domain of definition, discontinuity, and oddness of functions. We also explain in detail how, after researching the properties of such functions, one can draw their graph; this is a crucial part in the process of understanding their nature. In the paper, we present some subjects that the first-year student in the exact sciences may not encounter. We try to clarify those subjects and show that such ideas are important in the understanding of non-continuous functions, as a part of studying analysis in general.

  12. Assembly sequencing with toleranced parts

    Energy Technology Data Exchange (ETDEWEB)

    Latombe, J.C. [Stanford Univ., CA (United States). Robotics Lab.; Wilson, R.H. [Sandia National Labs., Albuquerque, NM (United States). Intelligent Systems and Robotics Center

    1995-02-21

    The goal of assembly sequencing is to plan a feasible series of operations to construct a product from its individual parts. Previous research has thoroughly investigated assembly sequencing under the assumption that parts have nominal geometry. This paper considers the case where parts have toleranced geometry. Its main contribution is an efficient procedure that decides if a product admits an assembly sequence with infinite translations that is feasible for all possible instances of the components within the specified tolerances. If the product admits one such sequence, the procedure can also generate it. For the cases where there exists no such assembly sequence, another procedure is proposed which generates assembly sequences that are feasible only for some values of the toleranced dimensions. If this procedure produces no such sequence, then no instance of the product is assemblable. Finally, this paper analyzes the relation between assembly and disassembly sequences in the presence of toleranced parts. This work assumes a simple, but non-trivial tolerance language that falls short of capturing all imperfections of a manufacturing process. Hence, it is only one step toward assembly sequencing with toleranced parts.

  13. Calculus: A Computer Oriented Presentation, Part 1 [and] Part 2.

    Science.gov (United States)

    Stenberg, Warren; Walker, Robert J.

    Parts one and two of a one-year computer-oriented calculus course (without analytic geometry) are presented. The ideas of calculus are introduced and motivated through computer (i.e., algorithmic) concepts. An introduction to computing via algorithms and a simple flow chart language allows the book to be self-contained, except that material on…

  14. Parts : ministrite minevik olgu avalik / Juhan Parts ; interv. Toomas Sildam

    Index Scriptorium Estoniae

    Parts, Juhan, 1966-

    2003-01-01

    Peaminister Juhan Parts vastab küsimustele, mis on seotud politseinike altkäemaksu andmise avalikuks tulekuga, komissar Indrek Sirgi ametist lahkumisega ja ministrite seadusrikkumiste avalikustamisega. Kommenteerivad: Margus Leivo, Tarmo Loodus, Ain Seppik. Vt. samas: Valik saladuses peetavast teabest

  15. Function Concepts for Machine Parts

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik

    1999-01-01

    The majority of resources, like time and costs, consumed in industrial product development can be related to detailed design, i.e. the materialisation of machine parts (German Maschinenteile). Existing design theories based on a systems approach, e.g. Haberfellner [5] all have function, i.......e. transformation from input to output or ability to deliver purposeful effects as the core concept. The units in a product which posses functions are the organs (German: Funktionsträgern). Because individual parts do not posses functions, one could argue that the design theories based on a systems approach...... to be identification of a purposeful behaviour concept, i.e. function for a machine part. The contribution is based on the theory of technical systems, Hubka and the domain theory, Andreasen....

  16. Update on rheumatology: part 1.

    Science.gov (United States)

    Neal-Boylan, Leslie

    2009-05-01

    There are many rheumatic diseases. Part 1 of this 2 part series on rheumatology presented a few of those most commonly seen in the community. Home health clinicians can be helpful in managing these diseases and preventing progression by watching for new symptoms or acute attacks of pain or disability, ensuring that patients take their medications appropriately, reminding patients to see their rheumatology providers and have their lab work done regularly, and reporting adverse effects to medications promptly. Additionally, as with most home health patients, an interdisciplinary approach that includes physical and occupational therapy, social work, nursing, nutrition, and other disciplines as needed should be implemented so that all patient needs are met and the patient is discharged at the highest level of self-care that is possible. Part 2 of this series will discuss the care of the patient with rheumatic disease at home and will provide a more in-depth look at lab diagnosis of rheumatic diseases.

  17. SPSS for Starters, Part 2

    CERN Document Server

    Cleophas, Ton J

    2012-01-01

    The first part of this title contained all statistical tests that are relevant for starters on SPSS, and included standard parametric and non-parametric tests for continuous and binary variables, regression methods, trend tests, and reliability and validity assessments of diagnostic tests. The current part 2 of this title reviews multistep methods, multivariate models, assessments of missing data, performance of diagnostic tests, meta-regression, Poisson regression, confounding and interaction, and survival analyses using log tests and segmented time-dependent Cox regression. Methods for asses

  18. Understanding quantitative research: part 1.

    Science.gov (United States)

    Hoe, Juanita; Hoare, Zoë

    This article, which is the first in a two-part series, provides an introduction to understanding quantitative research, basic statistics and terminology used in research articles. Critical appraisal of research articles is essential to ensure that nurses remain up to date with evidence-based practice to provide consistent and high-quality nursing care. This article focuses on developing critical appraisal skills and understanding the use and implications of different quantitative approaches to research. Part two of this article will focus on explaining common statistical terms and the presentation of statistical data in quantitative research.

  19. Small Bowel Review - Part I

    Directory of Open Access Journals (Sweden)

    ABR Thomson

    1997-01-01

    Full Text Available Significant advances have been made in the study of the small bowel. Part I of this two-part review of the small bowel examines carbohydrates, including brush border membrane hydrolysis and sugar transport; amino acids, dipeptides, proteins and food allergy, with a focus on glutamine, peptides and macromolecules, and nucleosides, nucleotides and polyamines; salt and water absorption, and diarrhea, including antidiarrheal therapy and oral rehydration treatment; lipids (digestion and absorption, fatty acid binding proteins, intracellular metabolism, lipoproteins and bile acids; and metals (eg, iron and vitamins.

  20. Ultrasonic Assembly of Thermoplastic Parts

    Energy Technology Data Exchange (ETDEWEB)

    Schurman, W. R.

    1970-03-31

    Four ultrasonic methods were evaluated for assembly of experimental plastic parts for detonators: (1) welding, (2) crimping and staking, (3) insertion, and (4) reactivation of adhesives. For welding, staking and insertion, plastics with low elastic moduli, such as acrylics and polycarbonate, produced the best results. Thermosetting, hot-melt, and solution adhesives could all be activated ultrasonically to form good bonds on plastics and other materials. This evaluation indicated that thermoplastic detonator parts could be assembled ultrasonically in shorter times than by present production techniques with high bond strengths and high product acceptance rates.

  1. An improved synthesis and biological evaluation of a new cage-like bifunctional chelator, 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1-ylamino)methyl) benzoic acid, for {sup 64}Cu radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Cai Hancheng; Li Zibo; Huang, C.-W.; Park, Ryan; Shahinian, Anthony H. [Molecular Imaging Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States); Conti, Peter S. [Molecular Imaging Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033 (United States)], E-mail: pconti@usc.edu

    2010-01-15

    Introduction: Stable attachment of {sup 64}Cu{sup 2+} to a targeting molecule usually requires the use of a bifunctional chelator (BFC). Sarcophagine (Sar) ligands rapidly coordinate {sup 64}Cu{sup 2+} within the multiple macrocyclic rings comprising the cage structure under mild conditions, providing high stability in vivo. Previously, we have designed a new versatile cage-like BFC Sar ligand, 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane-1-ylamino)methyl) benzoic acid (AmBaSar), for {sup 64}Cu radiopharmaceuticals. Here we report the improved synthesis of AmBaSar, {sup 64}Cu{sup 2+} labeling conditions and its biological evaluation compared with the known BFC 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). Methods: The AmBaSar was synthesized in four steps starting from (1,8-diamine-Sar) cobalt(III) pentachloride ([Co(DiAmSar)]Cl{sub 5}) using an improved synthetic method. The AmBaSar was labeled with {sup 64}Cu{sup 2+} in pH 5.0 ammonium acetate buffer solution at room temperature, followed by analysis and purification with HPLC. The in vitro stability of {sup 64}Cu-AmBaSar complex was evaluated in phosphate buffered saline (PBS), fetal bovine serum and mouse blood. The microPET imaging and biodistribution studies of {sup 64}Cu-AmBaSar were performed in Balb/c mice, and the results were compared with {sup 64}Cu-DOTA. Results: The AmBaSar was readily prepared and characterized by MS and {sup 1}H NMR. The radiochemical yield of {sup 64}Cu-AmBaSar was {>=}98% after 30 min of incubation at 25 deg. C. The {sup 64}Cu-AmBaSar complex was analyzed and purified by HPLC with a retention time of 17.9 min. The radiochemical purity of {sup 64}Cu-AmBaSar was more than 97% after 26 h of incubation in PBS or serum. The biological evaluation of {sup 64}Cu-AmBaSar in normal mouse demonstrated renal clearance as the primary mode of excretion, with improved stability in vivo compared to {sup 64}Cu-DOTA. Conclusions: The

  2. Air Pollution Control, Part I.

    Science.gov (United States)

    Strauss, Werner, Ed.

    Authoritative reviews in seven areas of current importance in air pollution control are supplied in this volume, the first of a two-part set. Titles contained in this book are: "Dispersion of Pollutants Emitted into the Atmosphere,""The Formation and Control of Oxides of Nitrogen in Air Pollution,""The Control of Sulfur Emissions from Combustion…

  3. Geometric design of part feeders

    NARCIS (Netherlands)

    Berretty, R.-P.M.

    2001-01-01

    This thesis presents solutions for problems derived from industrial assembly and robotic manipulation. The basic tasks in a factory are manufacturing the parts, and combining them into the desired product. In automating these tasks, we want to use robot manipulators that require little or no h

  4. Parts loob superametit / Koit Brinkmann

    Index Scriptorium Estoniae

    Brinkmann, Koit

    2007-01-01

    Majandus- ja kommunikatsiooniminister Juhan Parts kavatseb 2008. aastal liita uueks ametiks viis järelvalveametkonda - konkurentsiameti, sideameti, raudteeinspektsiooni, energiaturu inspektsiooni ja tehnilise järelevalve inspektsiooni - eesmärgiks on kulude kokkuhoid ning tõhusam kontroll monopolide üle. Kommenteerivad Valdo Kalm, Meelis Atonen. Lisa: Number. Vt. samas: Intervjuu majandus- ja kommunikatsiooniministri Juhan Partsiga

  5. Speech parts as Poisson processes.

    Science.gov (United States)

    Badalamenti, A F

    2001-09-01

    This paper presents evidence that six of the seven parts of speech occur in written text as Poisson processes, simple or recurring. The six major parts are nouns, verbs, adjectives, adverbs, prepositions, and conjunctions, with the interjection occurring too infrequently to support a model. The data consist of more than the first 5000 words of works by four major authors coded to label the parts of speech, as well as periods (sentence terminators). Sentence length is measured via the period and found to be normally distributed with no stochastic model identified for its occurrence. The models for all six speech parts but the noun significantly distinguish some pairs of authors and likewise for the joint use of all words types. Any one author is significantly distinguished from any other by at least one word type and sentence length very significantly distinguishes each from all others. The variety of word type use, measured by Shannon entropy, builds to about 90% of its maximum possible value. The rate constants for nouns are close to the fractions of maximum entropy achieved. This finding together with the stochastic models and the relations among them suggest that the noun may be a primitive organizer of written text.

  6. Theorem of Mystery: Part 2

    Science.gov (United States)

    Lopez-Real, Francis

    2008-01-01

    The Varignon parallelogram has always provided a simple geometric investigation for students that gives rise to a surprising result. It is possible to extend the Varignon investigation by looking at special quadrilaterals or by considering different dissection points along the sides. In the second of his two-part series, the author offers some…

  7. Piecing Together a College Education behind Bars. Part One [and] Part Two [and] Part Three [and] Part Four.

    Science.gov (United States)

    Taylor, Jon Marc

    2002-01-01

    This is a four-part article on how to earn a college degree from inside prison. The author, who earned his master's while in prison, argues that education offers prisoners the best chance of staying out of prison after their release, as well as qualifying them for a decent job and easing social reintegration. The author outlines the approaches…

  8. Local Area Networks: Part II.

    Science.gov (United States)

    Dessy, Raymond E., Ed.

    1982-01-01

    Discusses five approaches used by industry/colleges to provide local area network (LAN) capabilities in the analytical laboratory: (1) mixed baseband bus network coupled to a star net; (2) broadband bus network; (3) ring network; (4) star network coupled to broadband net; and (5) simple multiprocessor center. Part I (September issue) focused on…

  9. Inaccessibility and subinaccessibility. In two parts. Part II (in Russian)

    CERN Document Server

    Kiselev, Alexander

    2011-01-01

    This work represents a translation from English into Russian of the second part of the monograph by Alexander Kiselev under the same title. It contains the proof (in ZF) of inaccessible cardinals nonexistence. The first edition of this work was published in 2000. This part II contains applications of the subinaccessible cardinals apparatus and its basic tools - theories of reduced formula spectra and matrices, disseminators and others, which are used here in this proof and are set forth now in their more transparent and refined form. Much attention is devoted to the more explicit and substantial development and cultivation of basic ideas, serving as grounds for all main constructions and reasonings. The proof of the theorem about inaccessible cardinals nonexistence is presented in its detailed exposition. Several easy consequences of this theorem and some well-known results are presented. Appropriated for specialists in Set Theory and Mathematical Logic, and also for teachers and students of faculties of the ...

  10. Inaccessibility and subinaccessibility. In two parts. Part I (in Russian)

    CERN Document Server

    Kiselev, Alexander

    2011-01-01

    This work represents a translation from English into Russian of the first part of the monograph by Alexander Kiselev under the same title, containing the proof (in ZF) of inaccessible cardinals nonexistence. The first edition of this work was published in 2000. This part contains the apparatus of subinaccessible cardinals and its basic tools - theories of reduced formula spectra and matrices, disseminators and others - which are used in this proof and are set forth now in their more transparent and detailed form. Much attention is devoted to the explicit and substantial development and cultivation of basic ideas, serving as grounds for all main constructions and reasonings. Appropriated for specialists in Set Theory and Mathematical Logic, and also for teachers and students of faculties of the mathematical profile.

  11. Cleaning of parts for new manufacturing and parts rebuilding

    Science.gov (United States)

    Doherty, Jeff

    1994-06-01

    Parts cleaning is the largest single expense, and the most time consuming activity, in rebuilding and new manufacturing. On average, 25% to 40% of the total labor and overhead burden is spent on cleaning. EPA and OSHA pressures add to the burden by making some methods and chemicals obsolete. Some of the processes and chemicals in current use will be curtailed and or outlawed in the future. How can a shops and industries make long term decisions or capital investments in cleaning and process improvements when the government keeps changing its rules? At the MART Corporation in Saint Louis, Missouri, we manufacture a line of cabinet-style batch cleaning machines known as Power Washers. Twenty years ago MART invented and patented the Power Washer process, a cleaning method that recycles wash solution and blasts contaminates as they are washed off the more heavily contaminated parts. Since the initial invention MART has continued to R&D the washing process and develop ancillary systems that comply with EPA and OSHA regulations. For applications involving new industrial parts or items requiring specification cleaned surfaces. MART provides filtration and solution conditioning systems, part drying operations, and triple rinsing. Units are available in stainless steel or higher alloys. We are not alone in the washer manufacturing business. You have many choices of cleaning solutions (no pun intended) which will perform in your operations and yield good results. As a manufacturer, we are interested in your success with our equipment. We have all heard the horror stories of companies having selected inappropriate cleaning systems and or processes which then brought the company to its knees, production wise. Assembly, appearance, warranty, and performance shortcomings of finished products can often be directly related to the cleaning process and its shortcomings.

  12. Part-time Work in International Perspective.

    Science.gov (United States)

    Thurman, Joseph E.; Trah, Gabriele

    1990-01-01

    Examines the reasons for part-time work and characteristics of part-time workers, legislative protection, national incentives to increase access to part-time jobs, and forms of part-time work. Explores arguments for and against part-time employment. (SK)

  13. The Emergence of Axial Parts

    Directory of Open Access Journals (Sweden)

    Peter Svenonius

    2007-01-01

    Full Text Available Many languages have specialized locative words or morphemes translating roughly into words like ‘front,’ ‘back,’ ‘top,’ ‘bottom,’ ‘side,’ and so on. Often, these words are used instead of more specialized adpositions to express spatial meanings corresponding to ‘behind,’ ‘above,’ and so on. I argue, on the basis of a cross-linguistic survey of such expressions, that in many cases they motivate a syntactic category which is distinct from both N and P, which I call AxPart for ‘Axial Part’; I show how the category relates to the words which instantiate it, and how the meaning of the construction is derived from the combination of P[lace] elements, AxParts, and the lexical material which expresses them.

  14. Modernizing medical photography, part 2.

    Science.gov (United States)

    Crompton, Paul

    2005-03-01

    Part 1 of this paper explored the origins of process activity mapping, one of the major tools currently being used to modernize patient pathways in the National Health Service in Great Britain. Within medical photography the current notion of modernization is inextricably linked to the development of digital technology. Whilst the core principle of capturing light on a sensitive medium remains as clear and relevant as ever, the mechanisms by which the image is processed and presented to the client have changed profoundly. Part 2 shows how the principles of lean thinking and process activity mapping can be utilized to harness the advantages of digital technology to provide a modern and appropriate medical photography service in a large disparate teaching hospital.

  15. Modernizing medical photography, part 1.

    Science.gov (United States)

    Crompton, Paul

    2004-12-01

    Government, media and public focus on waiting times in the National Health Service in the United Kingdom has forced the organization to look closely at the process by which a patient progresses through an increasingly complex and ever changing system. In an effort to streamline the patient journey or care pathway, modernizers have turned to business and manufacturing for solutions. Whilst medical photographers need to recognize their role in this context, they are also facing major technological modernization through the development of digital photography. Part 1 of this paper looks at the origins of some of the techniques presently being used to modernize the patient journey. Part 2 shows how these tools of modernization can be utilized to harness the advantages of digital technology to provide a modern and appropriate medical photography service in a large, disparate teaching hospital.

  16. Counterfeit Parts Prevention Strategies Guide

    Science.gov (United States)

    2014-06-24

    as part of an International Standards Organization ( ISO ) 9001 :200818 or AS9100C19 quality management system. The third and fourth steps, Reporting...when problems are detected after delivery. Companies operating to ISO 9001 or other QMS processes may need to enhance customer reporting practices...Critical Ground Support Hardware ISO - 9001 Quality Management System - Requirements ISO /IEC 17025 General Requirements for the Competence of Testing and

  17. Repair Types, Procedures - Part 1

    Science.gov (United States)

    2010-05-01

    New Jersey, USA. Repair Types, Procedures – Part I RTO-EN-AVT-156 9 - 19 [5] Drieker R, Botello C, MacBeth S, and Grody J, “Aircraft Battle... MacBeth S, and Grody J, “Aircraft Battle Damage Assessment and Repair (ABDAR), Vol. III: Field Test Report,” AFRL-HE-WP-TR-2002-0039, July 2000. [8

  18. Body part categorisation in Punjabi

    OpenAIRE

    Majid, A.

    2006-01-01

    A key question in categorisation is to what extent people categorise in the same way, or differently. This paper examines categorisation of the body in Punjabi, an Indo-European language spoken in Pakistan and India. First, an inventory of body part terms is presented, illustrating how Punjabi speakers segment and categorise the body. There are some noteworthy terms in the inventory, which illustrate categories in Punjabi that are unusual when compared to other languages presented in this vol...

  19. EMC Part Ⅱ Regulatory Requirements

    Institute of Scientific and Technical Information of China (English)

    JohnWong

    2005-01-01

    As described in the Part I, the goal of electromagnetic compatibility, or EMC, is to design electronic systems that are electromagnetically compatible with their environment. EMC requirements exist so that electronic systems designers have a set of guidelines that explain the limits of what is considered electromagnetically compatible. There is not, however, one allencompassing set of EMC guidelines. Instead, EMC guidelines are created by individual product manufacturers,

  20. Automotive stamped part fatigue design

    Directory of Open Access Journals (Sweden)

    Caudoux Mélanie

    2014-06-01

    Full Text Available Fatigue design of automotive axle parts is of prior concern because of these are high safety parts and they are expected to drive the overall vehicle mass reduction. In this framework, the stamping process is widely used to form axle parts, before assembling them by welding. Consequently, the mechanical and physical characteristics of the blank sheet are modified, having a strong influence on the fatigue behavior. In this paper, we address the consequences of the stamped process on the fatigue design and how they may be effectively taken into account in the automotive industry. Actually, the coupling between the stamping process and the fatigue design is under development at PSA Peugeot Citroën Company since several years. Such an analysis deals with some major topics: thickness variation, plastic hardening and deformation, and residual stress. All of these ingredients result in fatigue criteria evolutions: it is important to stress that the stamping process can have advantageous or disadvantageous consequences on the fatigue design. This is here highlighted on some examples, dealing with front and rear axles.

  1. NASA EEE Parts 2014 Year in Review

    Science.gov (United States)

    Lee, Sara-Anne

    2015-01-01

    The NASA Electronic Parts and Packaging Program continue to support Electrical, Electronic and Electromagnetic Parts for the agency with an eventful year of workshops, innovations, testing and challenges.

  2. Experimental Data Processing. Part 2

    Directory of Open Access Journals (Sweden)

    Wilhelm LAURENZI

    2011-03-01

    Full Text Available This paper represents the second part of a study regarding the processing of experimental monofactorialdata, and it presents the original program developed by the author for processing experimental data.Using consecrated methods and relations, this program allows establishing the number of samples,generating the experimental plan, entering and saving the measured data, identifying the data corrupted byaberrant errors, verifying the randomness, verifying the normality of data repartition, calculating the mainstatistical parameters and exporting the experimental data to Excel or to other programs for statistical dataprocessing.

  3. The Sum of its Parts

    Science.gov (United States)

    Spriggs, John

    A safety case is a collation of the arguments and supporting evidence needed to demonstrate that an item is safe to use. Although there are regulatory and legislative requirements in some industries, and in some parts of the world, for the production of a safety case, there are few standard definitions of what should go into one. Indeed, there is no single, correct, way to prepare a safety case; but this should not be surprising, given the wide variety of applications to which they are put.

  4. The Inconvenient Truth. Part 2

    Energy Technology Data Exchange (ETDEWEB)

    Athanasiou, T.

    2007-01-15

    Essay-type of publication on what should happen next after Al Gore's presentations on the Inconvenient Truth about the impacts of climate change. The essay states in the first lines: 'We've seen the movie, so we know the first part - we're in trouble deep. And it's time, past time, for at least some of us to go beyond warning to planning, to start talking seriously about a global crash program to stabilize the climate.

  5. Part time secretarial assistant needed

    CERN Document Server

    2004-01-01

    The English National Programme at the Lycée International, Ferney-Voltaire, one of the Programmes originally set up by CERN to provide schooling for children of Members of the Personnel in their maternal language, is recruiting a part time secretarial assistant. Applications for this post should be sent as soon as possible. The closing date is the end of the day on July 19th. Applicants will find details on the ‘Staff Vacancies' page of our website: http://enpferney.org/

  6. Two-part set systems

    CERN Document Server

    Gerbner, Dániel; Lemons, Nathan; Mubayi, Dhruv; Palmer, Cory; Patkós, Balázs

    2011-01-01

    The two part Sperner theorem of Katona and Kleitman states that if $X$ is an $n$-element set with partition $X_1 \\cup X_2$, and $\\cF$ is a family of subsets of $X$ such that no two sets $A, B \\in \\cF$ satisfy $A \\subset B$ (or $B \\subset A$) and $A \\cap X_i=B \\cap X_i$ for some $i$, then $|\\cF| \\le {n \\choose \\lfloor n/2 \\rfloor}$. We consider variations of this problem by replacing the Sperner property with the intersection property and considering families that satisfiy various combinations of these properties on one or both parts $X_1$, $X_2$. Along the way, we prove the following new result which may be of independent interest: let $\\cF, \\cG$ be families of subsets of an $n$-element set such that $\\cF$ and $\\cG$ are both intersecting and cross-Sperner, meaning that if $A \\in \\cF$ and $B \\in \\cG$, then $A \

  7. Standards in neurosonology. Part III

    Directory of Open Access Journals (Sweden)

    Joanna Wojczal

    2016-06-01

    Full Text Available The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specific brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler. Part II and III are devoted to standards for specific clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-to-left shunts, confirmation of the arrest of the cerebral circulation, an assessment of the functional efficiency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity.

  8. Standards in neurosonology. Part III.

    Science.gov (United States)

    Wojczal, Joanna; Tomczyk, Tomasz; Luchowski, Piotr; Kozera, Grzegorz; Kaźmierski, Radosław; Stelmasiak, Zbigniew

    2016-06-01

    The paper presents standards related to ultrasound imaging of the cerebral vasculature and structures. The aim of this paper is to standardize both the performance and description of ultrasound imaging of the extracranial and intracranial cerebral arteries as well as a study of a specific brain structure, i.e. substantia nigra hyperechogenicity. The following aspects are included in the description of standards for each ultrasonographic method: equipment requirements, patient preparation, study technique and documentation as well as the required elements of ultrasound description. Practical criteria for the diagnosis of certain pathologies in accordance with the latest literature were also presented. Furthermore, additional comments were included in some of the sections. Part I discusses standards for the performance, documentation and description of different ultrasound methods (Duplex, Doppler). Part II and III are devoted to standards for specific clinical situations (vasospasm, monitoring after the acute stage of stroke, detection of a right-to-left shunts, confirmation of the arrest of the cerebral circulation, an assessment of the functional efficiency of circle of Willis, an assessment of the cerebrovascular vasomotor reserve as well as the measurement of substantia nigra hyperechogenicity).

  9. Facilitation of learning: part 2.

    Science.gov (United States)

    Warburton, Tyler; Houghton, Trish; Barry, Debbie

    2016-04-27

    The previous article in this series of 11, Facilitation of learning: part 1, reviewed learning theories and how they relate to clinical practice. Developing an understanding of these theories is essential for mentors and practice teachers to enable them to deliver evidence-based learning support. This is important given that effective learning support is dependent on an educator who possesses knowledge of their specialist area as well as the relevent tools and methods to support learning. The second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice relates to the facilitation of learning. To fulfil this domain, mentors and practice teachers are required to demonstrate their ability to recognise the needs of learners and provide appropriate support to meet those needs. This article expands on some of the discussions from part 1 of this article and considers these from a practical perspective, in addition to introducing some of the tools that can be used to support learning.

  10. Future Jet Technologies, Part C

    Science.gov (United States)

    Gal-Or, Benjamin

    2013-06-01

    This updated, PART C REVIEW, covers the dangerous global spread of JS-stealth, drone technology [1-91], canard-free, stealth, new agile drones and the highly debated, 480 billion F-35 International Program as reported on March 13, 2013 to the U.S. Congress [92]. Due to serious design issues, spiraling high costs and years in delays, alternatives are analyzed here, depicted and proposed, mainly from the propulsion-design point of view. These include fleets of low-cost, stealth, jet-steered-drones mixed with non-stealthy, low-cost, ready-to-be-delivered, U.S. or European or Russian fighter aircraft. Can a few F-35s win against large fleets of stealth agile drones? To understand the dangers and critical issues involved, the author's own, past classified information is partly disclosed, while resorting to images in Figs. 2(a) and 2(b) taken from his book [2] and from Wikipedia, the "Free Encyclopedia", in all other images.

  11. Tool sharing in parallel part production

    NARCIS (Netherlands)

    Gaalman, G.J.C.; Nawijn, W.M.

    1996-01-01

    A group of identical NC machines, laid out in a line, manufactures relatively few part types in large batch size. Parts of the same type are processed by the machines simultaneously. The operations on a part are performed by one machine only, using a part type specific tool set. During batch product

  12. 30 CFR 33.38 - Electrical parts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical parts. 33.38 Section 33.38 Mineral... § 33.38 Electrical parts. (a) Units with electrical parts and designed to operate as electric face... which is Schedule 2F), and the examination and testing of the electrical parts shall be...

  13. 20 CFR 726.3 - Relationship of this part to other parts in this subchapter.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Relationship of this part to other parts in...; REQUIREMENTS FOR COAL MINE OPERATOR'S INSURANCE General § 726.3 Relationship of this part to other parts in...) If the provisions of this part appear to conflict with any provision of any other part in...

  14. Development of methods for the selective separation of scandium, zirconium and tin for radiopharmaceutical applications; Entwicklung von Methoden zur selektiven Trennung von Scandium, Zirkonium und Zinn fuer radiopharmazeutische Anwendungen

    Energy Technology Data Exchange (ETDEWEB)

    Dirks-Fandrei, Carina

    2014-07-01

    to have a good potential for this use. Another part of this work is dealing with the preparation and application of an extraction chromatographic resin based on the use of multi-walled nanotubes. It could be shown that resins based on nanotubes do have some interesting properties; but it could also be shown that of such resins have some distinct disadvantages especially with respect to their practical use. Packing a column with nanotubes based materials is far more challenging then packing a column with classical resin. Achieving flow rates sufficiently high for their foreseen use turned out to be difficult to achieve.

  15. Revenue cycle management, Part II.

    Science.gov (United States)

    Crew, Matt

    2007-01-01

    The proper management of your revenue cycle requires the application of "best practices" and the continual monitoring and measuring of the entire cycle. The correct technology will enable you to gain the insight and efficiencies needed in the ever-changing healthcare economy. The revenue cycle is a process that begins when you negotiate payor contracts, set fees, and schedule appointments and continues until claims are paid in full. Every single step in the cycle carries equal importance. Monitoring all phases and a commitment to continually communicating the results will allow you to achieve unparalleled success. In part I of this article, we explored the importance of contracting, scheduling, and case management as well as coding and clinical documentation. We will now take a closer look at the benefits charge capture, claim submission, payment posting, accounts receivable follow-up, and reporting can mean to your practice.

  16. Biodistribution of the radiopharmaceutical sodium pertechnetate (Na{sup 99m}TcO{sub 4}) after massive small bowel resection in rats; Biodistribuicao do radiofarmaco pertecnetato de sodio (Na{sup 99m}TcO{sub 4}) em ratos submetidos a resseccao extensa de intestino delgado

    Energy Technology Data Exchange (ETDEWEB)

    Chacon, Damaso de Araujo; Araujo-Filho, Irami; Villarim-Neto, Arthur; Brandao-Neto, Jose; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Programa de Pos-graduacao em Ciencias da Saude]. E-mail: damasochacon@uol.com.br; Rego, Amalia Cinthia Meneses [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Programa de Iniciacao Cientifica; Azevedo, Italo Medeiros [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Cirurgia; Bernardo-Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Dept. de Biofisica e Biometria

    2007-11-15

    , if an examination using this radiopharmaceutical is indicated. (author)

  17. Room for Sustainable Agriculture. Part 1 Advice. Part 2 Analysis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-03-15

    An outline is given of the social dilemmas associated with agriculture and horticulture in the Netherlands. Ongoing innovation and accelerated sustainable development are essential to resolve these dilemmas. Given the importance of the Dutch agriculture and horticulture sector, there is every reason for the central government to play its part and help remove the obstacles to the continuing sustainable development of the sector. The Council recommends that the central government continues developing the Council's vision for agriculture and horticulture with the parties concerned, allows scope for the development of different agricultural business models, applies knowledge and innovation as drivers of continuing sustainable development, amends laws and regulations as necessary, and facilitates a permanent dialogue between the sector and society. The advisory report also sets out the Council's vision concerning the political and public debate on agriculture and horticulture. This debate is most clearly characterised by major and seemingly insurmountable differences of opinion. The Council hopes that its report will induce a shift in thinking about Dutch agriculture among politicians and society at large, so that the transitions considered necessary by the Council can be implemented more rapidly.

  18. 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.

  19. 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.

  20. Somos parte de la crisis?

    Directory of Open Access Journals (Sweden)

    Ingeniería e Investigación Revista

    2011-06-01

    Full Text Available Muchos años estuvimos resistiéndonos a aceptar la difícil situación que en todos los órdenes vivía el país. Finalmente, y como consecuencia de intereses ajenos a los que realmente debían guiarnos, estalló o quizá sea mejor decir, se agudizo la crisis del sistema. El tema no es nuevo, y recabar sobre el mismo, no pasaría, en el mejor de los casos, de ser un simple mea-culpa que dudamos aporte luces a la solución del problema. Sin embargo, pretender cerrar los ojos frente a la crisis, también resulta imposible, y mas aun, cuando la consecuencia directa de ella se refleja en la perdida, cada vez mayor, de confianza de la ciudadanía en todos los estamentos de la nación, pero fundamentalmente porque institucionalmente somos parte de ella.

  1. Higher Spin Theory -- Part I

    CERN Document Server

    Rahman, Rakibur

    2013-01-01

    These notes comprise a part of the introductory lectures on Higher Spin Theory presented in the Eighth Modave Summer School in Mathematical Physics. We construct free higher-spin theories and turn on interactions to find that inconsistencies show up in general. Interacting massless fields in flat space are in tension with gauge invariance and this leads to various no-go theorems. While massive fields exhibit superluminal propagation, appropriate non-minimal terms may cure such pathologies as they do in String Theory -- a fact that we demonstrate. Given that any interacting massive higher-spin particle is described by an effective field theory, we compute a model independent upper bound on the ultraviolet cutoff in the case of electromagnetic coupling in flat space and discuss its implications. Finally, we consider various possibilities of evading the no-go theorems for massless fields, among which Vasiliev's higher-spin gauge theory is one. We work out a simple example of a higher-derivative cubic coupling in...

  2. Drilling miniature holes, Part III

    Energy Technology Data Exchange (ETDEWEB)

    Gillespie, L.K.

    1978-07-01

    Miniature components for precision electromechanical mechanisms such as switches, timers, and actuators typically require a number of small holes. Because of the precision required, the workpiece materials, and the geometry of the parts, most of these holes must be produced by conventional drilling techniques. The use of such techniques is tedious and often requires considerable trial and error to prevent drill breakage, minimize hole mislocation and variations in hole diameter. This study of eight commercial drill designs revealed that printed circuit board drills produced better locational and size repeatability than did other drills when centerdrilling was not used. Boring holes 1 mm in dia, or less, as a general rule did not improve hole location in brass or stainless steel. Hole locations of patterns of 0.66-mm holes can be maintained within 25.4-..mu..m diametral positional tolerance if setup misalignments can be eliminated. Size tolerances of +- 3.8 ..mu..m can be maintained under some conditions when drilling flat plates. While these levels of precision are possible with existing off-the-shelf drills, they may not be practical in many cases.

  3. Getting from Organ- to Part- Structure

    DEFF Research Database (Denmark)

    Andreasen, Mogens Myrup; Mortensen, Niels Henrik

    1997-01-01

    The paper gives definitions of organ and part and elaborate on the relations between organ, parts and production methods. The importance of the law of superimposed structures on part design is illustrated and a domain- and view concept is developed.The paper is a collective of overhead-copies, pu......The paper gives definitions of organ and part and elaborate on the relations between organ, parts and production methods. The importance of the law of superimposed structures on part design is illustrated and a domain- and view concept is developed.The paper is a collective of overhead...

  4. Range Imaging without Moving Parts

    Science.gov (United States)

    Blair, J. Bryan; Scott, V. Stanley, III; Ramos-Izquierdo, Luis

    2008-01-01

    Range-imaging instruments of a type now under development are intended to generate the equivalent of three-dimensional images from measurements of the round-trip times of flight of laser pulses along known directions. These instruments could also provide information on characteristics of targets, including roughnesses and reflectivities of surfaces and optical densities of such semi-solid objects as trees and clouds. Unlike in prior range-imaging instruments based on times of flight along known directions, there would be no moving parts; aiming of the laser beams along the known directions would not be accomplished by mechanical scanning of mirrors, prisms, or other optical components. Instead, aiming would be accomplished by using solid-state devices to switch input and output beams along different fiber-optic paths. Because of the lack of moving parts, these instruments could be extraordinarily reliable, rugged, and long-lasting. An instrument of this type would include an optical transmitter that would send out a laser pulse along a chosen direction to a target. An optical receiver coaligned with the transmitter would measure the temporally varying intensity of laser light reflected from the target to determine the distance and surface characteristics of the target. The transmitter would be a combination of devices for generating precise directional laser illumination. It would include a pulsed laser, the output of which would be coupled into a fiber-optic cable with a fan-out and solid-state optical switches that would enable switching of the laser beam onto one or more optical fibers terminated at known locations in an array on a face at the focal plane of a telescope. The array would be imaged by the telescope onto the target space. The receiver optical system could share the aforementioned telescope with the transmitter or could include a separate telescope aimed in the same direction as that of the transmitting telescope. In either case, light reflected

  5. The genus Allium. Part 2.

    Science.gov (United States)

    Fenwick, G R; Hanley, A B

    1985-01-01

    Allium is a genus of some 500 species belonging to the family Liliaceae. However only a few of these are important as food plants, notably onion, garlic, chive, leek, and rakkyo. Such plants have been used for many centuries for the pungency and flavoring value, for their medicinal properties, and, in some parts of the world, their use also has religious connotations. The flavors of members of the genus Alliums, in addition to having certain characteristics, are also complex, being derived enzymically from a number of involatile precursors. In addition to there being variation of flavor between different alliums, there are also considerable changes that occur as a result of cooking and processing. Of course, these are of importance to the consumer and food technologist-processor. The review will introduce the subject by an historical perspective and will set this against data on the present cultivation and usage of commercially cultivated alliums. The chemical composition of these plants will be discussed, emphasis being given to nonvolatile constituents which are, perhaps, less often considered. Discussion of the volatile constituents, which will include mention of the methods currently used for their analysis and for the determination of "flavor strength", will be mainly concerned with literature taken from the last 5 years. In considering the extent and nature of allium cultivation and processing, factors affecting the nutritional value and quality will be highlighted. The medicinal properties of garlic and onion oils have been much studied over the last decade and the review will include critical assessment of this area and also will touch on the more general properties (antimicrobial, antifungal, antibacterial, and insecticidal) of these oils. Finally mention will be made of the antinutritional, toxic, or otherwise undesirable effects of alliums, for example, as inadvertent components of animal diets, tainting of milk and other food products. It is our

  6. Primer for Purchasing Computer Programs: Part 3.

    Science.gov (United States)

    Delf, Robert M.

    1981-01-01

    The last section of a three-part series deals with computer hardware requirements, program installation, and evaluation techniques. The first two parts appeared in the July and September 1981 issues. (Author/MLF)

  7. The Progressing Auto Parts Sector in China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The auto parts sector was not only the basis for the entire auto industry in China, but continues to be an important part of industry development. China's auto parts sector had lagged behind the world's auto industry for a long time; however, since the start of the new century, the country's auto parts sector has been put on a fast track to meet the rapid growth in the auto industry.

  8. Using GPU shaders for visualization, part 3.

    Science.gov (United States)

    Bailey, Mike

    2013-01-01

    GPU shaders aren't just for glossy special effects. Parts 1 and 2 of this discussion looked at using them for point clouds, cutting planes, line integral convolution, and terrain bump-mapping. Part 3 covers compute shaders and shader storage buffer objects-two features announced as part of OpenGL 4.3.

  9. Expertise revisited, Part I-Interactional expertise.

    Science.gov (United States)

    Collins, Harry; Evans, Robert

    2015-12-01

    In Part I of this two part paper we try to set out the 'essence' of the notion of interactional expertise by starting with its origins. In Part II we will look at the notion of contributory expertise. The exercise has been triggered by recent discussion of these concepts in this journal by Plaisance and Kennedy and by Goddiksen.

  10. Expertise revisited, Part II: Contributory expertise.

    Science.gov (United States)

    Collins, Harry; Evans, Robert; Weinel, Martin

    2016-04-01

    In Part I of this two part paper we tried to elicit the 'essence' of the notion of interactional expertise by looking at its origins. In Part II we will look at the notion of contributory expertise. The exercise has been triggered by recent discussion of these concepts in this journal by Plaisance and Kennedy and by Goddiksen.

  11. 14 CFR 27.602 - Critical parts.

    Science.gov (United States)

    2010-01-01

    ... STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction General § 27.602 Critical parts. (a) Critical... the required level of integrity. (b) If the type design includes crtical parts, a critical parts list shall be established. Procedures shall be established to define the critical design...

  12. 14 CFR 29.602 - Critical parts.

    Science.gov (United States)

    2010-01-01

    ... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction General § 29.602 Critical parts. (a... required level of integrity. (b) If the type design includes critical parts, a critical parts list shall be established. Procedures shall be established to define the critical design characteristics, identify...

  13. Parts, Cavities, and Object Representation in Infancy

    Science.gov (United States)

    Hayden, Angela; Bhatt, Ramesh S.; Kangas, Ashley; Zieber, Nicole

    2011-01-01

    Part representation is not only critical to object perception but also plays a key role in a number of basic visual cognition functions, such as figure-ground segregation, allocation of attention, and memory for shapes. Yet, virtually nothing is known about the development of part representation. If parts are fundamental components of object shape…

  14. TSUNAMI INFORMATION SOURCES - PART 4

    Directory of Open Access Journals (Sweden)

    Robert L. Wiegel

    2006-01-01

    Full Text Available I have expanded substantially my list of information sources on: tsunami generation (sources, impulsive mechanisms, propagation, effects of nearshore bathymetry, and wave run-up on shore - including physical (hydraulic modeling and numerical modeling. This expanded list includes the subjects of field investigations of tsunamis soon after an event; damage effects in harbors on boats, ships, and facilities; tsunami wave-induced forces; damage by tsunami waves to structures on shore; scour/erosion; hazard mitigation; land use planning; zoning; siting, design, construction and maintenance of structures and infrastructure; public awareness and education; distant and local sources; tsunami warning and evacuation programs; tsunami probability and risk criteria. A few references are on "sedimentary signatures" useful in the study of historic and prehistoric tsunamis (paleo-tsunamis. In addition to references specifically on tsunamis, there are references on long water wave and solitary wave theory; wave refraction, diffraction, and reflection; shelf and basin free and forced oscillations (bay and harbor response; seiches; edge waves; Mach- reflection of long water waves ("stem waves"; wave run-up on shore; energy dissipation. All are important in understanding tsunamis, and in hazard mitigation. References are given on subaerial and submarine landslide (and rockfall generated waves in reservoirs, fjords, bays, and ocean; volcano explosive eruptions/collapse; underwater and surface explosions; asteroid impact. This report is in two parts: 1 Bibliographies, books and pamphlets, catalogs, collections, journals and newsletters, maps, organizations, proceedings, videos and photos; 2 Articles, papers, reports listed alphabetically by author.Many papers on the Indian Ocean (Sumatra tsunami of 26 December 2004, were given at the 22nd IUGG International Tsunami Symposium, Chania, Crete, 27-29 June 2005, but had not been published at the date of this report. For

  15. Asmparts: assembly of biological model parts.

    Science.gov (United States)

    Rodrigo, Guillermo; Carrera, Javier; Jaramillo, Alfonso

    2007-12-01

    We propose a new computational tool to produce models of biological systems by assembling models from biological parts. Our software not only takes advantage of modularity, but it also enforces standardisation in part characterisation by considering a model of each part. We have used model parts in SBML to design transcriptional networks. Our software is open source, it works in linux and windows platforms, and it could be used to automatically produce models in a server. Our tool not only facilitates model design, but it will also help to promote the establishment of a registry of model parts.

  16. The specific uptake size index for quantifying radiopharmaceutical uptake

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, John S [Department of Medical Physics and Bioengineering, Southampton University Hospitals NHS Trust, Southampton (United Kingdom); Bolt, Livia [Department of Medical Physics and Bioengineering, Southampton University Hospitals NHS Trust, Southampton (United Kingdom); Stratford, Jennifer S [Department of Medical Physics and Bioengineering, Southampton University Hospitals NHS Trust, Southampton (United Kingdom); Kemp, Paul M [Department of Nuclear Medicine, Southampton University Hospitals NHS Trust, Southampton (United Kingdom)

    2004-07-21

    Quantitative indices of radionuclide uptake in an object of interest provide a useful adjunct to qualitative interpretation in the diagnostic application of radionuclide imaging. This note describes a new measure of total uptake of an organ, the specific uptake size index (SUSI). It can either be related in absolute terms to the total activity injected or to the specific activity in a reference region. As it depends on the total activity in the object, the value obtained will not depend on the resolution of the imaging process, as is the case with some other similar quantitative indices. This has been demonstrated in an experiment using simulated images. The application of the index to quantification of dopamine receptor SPECT imaging and parathyroid-thyroid subtraction planar scintigraphy is described. The index is considered to be of potential value in reducing variation in quantitative assessment of uptake in objects with applications in all areas of radionuclide imaging. (note)

  17. PET/CT in prostate cancer: non-choline radiopharmaceuticals.

    Science.gov (United States)

    Castellucci, P; Jadvar, H

    2012-08-01

    In this brief review, the major potential clinical applications of 18F-FDG, 11C-acetate, 18F-FDHT, 18F-FLT, 18F-FMAU, and anti-18F-FACBC in the imaging evaluation of men with prostate cancer are discussed. 18F-FDG has a limited role in primary diagnosis and staging but it may be able to reflect tumour aggressiveness, detect sites of recurrence in some men with high serum PSA after biochemical failure and assess response to chemo- and hormonal treatment in metastatic disease. 11C-acetate has been investigated for intra-prostatic primary tumour detection and staging as well as for re-staging in case of biochemical relapse with results that are overall similar to those with 18F- and 11C-labeled choline. 18F-FDHT targets the androgen receptor and may be particularly useful in the assessment of the pharmacodynamics of the androgen signalling pathway. PET in conjunction with 18F-FLT or 18F-FMAU that track the thymidine salvage pathway of DNA synthesis has also been investigated for imaging cellular proliferation in prostate cancer. Initial experience with the radiolabeled synthetic amino acid, anti-18F-FACBC, which displays slow urinary excretion has been encouraging but further studies will be needed to decipher its exact role in the imaging management of men with prostate cancer.

  18. Radiopharmaceuticals for renal function imaging; Radiopharmaka fuer die Nierenfunktionsdiagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Brandau, W. [Klinik fuer Nuklearmedizin, Arbeitsgruppe Nuklearchemie und Radiopharmazie, Universitaetsklinikum Essen (Germany)

    2003-09-01

    Due to its favourable physical properties, [{sup 99m}Tc]Technetium is the mostly used radionuclide in nuclear medicine. It can only be used as metal complexes, whose pharmacokinetics cannot be predicted easily. By systematic variations of a known compound, Tc-complexes could be synthesized which are actively excreted by the kidneys. Thus, on the one hand, the tubular extraction rate can now be quantified in addition to the glomerular filtration rate and on the other hand, scintigraphic imaging is possible by the use of Tc-pharmaceuticals, which are eliminated by active tubular transport. (orig.) [German] [{sup 99m}Tc]Technetium ist aufgrund seiner optimalen physikalischen Eigenschaften fuer die Bildgebung das meistverwendete Radionuklid in der Nuklearmedizin. Es kann aber nur in Form von Metallkomplexen eingesetzt werden, deren in vivo Verhalten schwer vorhersagbar ist. In den letzten Jahren ist es jedoch durch systematische Variation einer Leitstruktur gelungen, Technetium-Radiopharmaka zu entwickeln, die renal aktiv transportiert werden. Dadurch kann einerseits neben der Glomerulaeren Filtrationsrate nun auch die Tubulaere Extraktionsrate quantifiziert werden, andererseits ist erstmals die Szintigraphie mit Technetiummarkierten Substanzen moeglich, die tubulaer sezerniert werden. (orig.)

  19. Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science)

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, M.; Beck, R.N.

    1992-06-01

    This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of (F18)fluorinated benzamides (dopamine D-2 receptor tracers), (F18)fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of (F18)-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.

  20. Compact cyclotrons for the production of tracers and radiopharmaceuticals

    NARCIS (Netherlands)

    Paans, AMJ

    2003-01-01

    Positron Emission Tomography (PET) is a method for determining biochemical and physiological processes in vivo in a quantitative manner. The most commonly used radionuclides are C-11, N-13, O-15 and F-18, with respective half-lives of approximately 20 min, 10 min, 2 min, and 110 min. F-18 labeled FD

  1. Evaluation of syringe shield effectiveness in handling radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Cho Yong-In

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the effectiveness of the radiation shield of radionuclide syringes and the personal dose equivalent by performing a simulation of radionuclides used in nuclear medicine diagnosis. In order to evaluate the dose depending on the distance between the radiation source and the ICRU sphere against the thickness of the shielding device, the distance at which a nuclear medicine worker may inadvertently come into contact with radiation from the radiation source was set at 0 cm to 30 cm according to the thickness of the shield, thus fixing the ICRU sphere. For a dose evaluation, Hp(10, Hp(3, and Hp(0.07 measurable in specific depth of the ICRU were evaluated. It was found that a dose measured on skin surface of nuclear medicine workers was relatively higher, that the dose varied in relation to the thickness of the radiation shield, and that the shielding effect decreased for some radiation sources such as 67Ga and 111In. It proved necessary to increase thickness of shielding device to the radiation sources such as 67Ga and 111In. It is also considered that a study of proper shielding thickness will be needed in future.

  2. Radiopharmaceuticals developed at the University of Missouri research reactor

    Energy Technology Data Exchange (ETDEWEB)

    Ketring, A.R.; Ehrhardt, G.J. [Univ. of Missouri, Columbia, MO (United States); Day, D.E. [Univ. of Missouri, Rolla, MO (United States)

    1997-12-01

    The University of Missouri Research Reactor (MURR) has put a great deal of effort in the last two decades into development of radiotherapeutic beta emitters as nuclear medicine radiotherapeutics for malignancies. This paper describes the development of two of these drugs, {sup 153}Sm ethylenediaminetetra-methylene phosphonic acid (EDTMP) (Quadramet{trademark}) and {sup 90}Y glass microspheres (TheraSphere{trademark}). Samarium-153 EDTMP is a palliative used to treat the pain of metastatic bone cancer without the side effects of narcotic pain killers. Yttrium-90 glass microspheres are delivered via hepatic artery catheter to embolize the capillaries of liver tumors and deliver a large radiation dose for symptom palliation and life prolonging purposes.

  3. Quantitative autoradiographic microimaging in the development and evaluation of radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Som, P. [Brookhaven National Lab., Upton, NY (United States); Oster, Z.H. [State Univ. of New York, Stony Brook, NY (United States)

    1994-04-01

    Autoradiographic (ARG) microimaging is the method for depicting biodistribution of radiocompounds with highest spatial resolution. ARG is applicable to gamma, positron and negatron emitting radiotracers. Dual or multiple-isotope studies can be performed using half-lives and energies for discrimination of isotopes. Quantitation can be performed by digital videodensitometry and by newer filmless technologies. ARG`s obtained at different time intervals provide the time dimension for determination of kinetics.

  4. Development of new radiopharmaceuticals for imaging monoamine oxidase B

    Energy Technology Data Exchange (ETDEWEB)

    Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca; Sadovski, Oleg; Moran, Matthew D.; Parkes, Jun; Meyer, Jeffrey H.; Houle, Sylvain; Wilson, Alan A.

    2011-10-15

    Introduction: Imaging monoamine oxidase B (MAO-B) in the central nervous system with PET is an important goal for psychiatric studies. We here report an improved and automated radiosynthesis of N-(6-[{sup 18}F]-fluorohexyl)-N-methylpropargylamine ([{sup 18}F]FHMP; [{sup 18}F]-1), as well as the radiosynthesis of two new promising candidates for imaging cerebral MAO-B, namely, carbon-11-labeled 3-(4-[{sup 11}C]-methoxyphenyl)-6-methyl-2H-1-benzopyran-2-one ([{sup 11}C]-2) and N-((1H-pyrrol-2-yl)methyl)-N-[{sup 11}C]-methyl-1-phenylmethanamine ([{sup 11}C]-3). Methods: Fluorine-18-labeled 1 was prepared via a tosyloxy precursor in 29%{+-}5% uncorrected radiochemical yield, relative to [{sup 18}F]-fluoride. Both carbon-11-labeled compounds were prepared with [{sup 11}C]CH{sub 3}I using the 'LOOP' method in 11% and 18% uncorrected radiochemical yields, respectively, relative to starting [{sup 11}C]CO{sub 2}. All radiotracers had specific activities >37 GBq/{mu}mol and were >98% radiochemically pure at end of synthesis (<40 min). All radiotracers were evaluated by ex vivo biodistribution studies in conscious rodents. Results: A major radioactive metabolite in the rodent brain was observed following administration of [{sup 18}F]-1. While [{sup 11}C]-2 had moderate brain penetration and good clearance from normal brain tissue, distribution of radioactivity in brain was indicative of free and nonspecific binding. Good brain uptake was observed with [{sup 11}C]-3 (0.8%-1.4% injected dose per gram at 5 min postinjection), binding appeared to be reversible and distribution conformed with regional distribution of MAO-B in the rat brain. Preinjection of 3 or L-deprenyl showed a modest reduction (up to 25%) of brain activity. Conclusion: Carbon-11-labeled 3 was found to have the most favorable properties of the radiotracers evaluated; however, the signal-to-noise ratio was too low to warrant further in vivo imaging studies. Alternative radiotracers for imaging MAO-B are under development.

  5. Preparation and quality control of {sup 153}Sm radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Swasono, R. Tamat; Widyastuti, W.; Purwadi, B.; Laksmi, I. [Radioisotope Production Center - BATAN, Jakarta (Indonesia)

    1998-10-01

    The paper summarizes the preparation and quality control of {sup 153}Sm-EDTMP and three {sup 153}Sm-radiosynovectomy agents. Natural and enriched Sm{sub 2}O{sub 3} (98.7% {sup 152}Sm) irradiated in RSG-GAS 30 MW reactor yielded pure and high specific activity {sup 153}Sm. Labeling of EDTMP with {sup 153}Sm was carried out by mixing {sup 153}SmCl{sub 3} solution of pH 4.0 to an EDTMP solution at room temperature then pH adjustment to 8. The {sup 153}Sm-EDTMP complex was separated from the free {sup 153}Sm{sup +3} on a Chelex 100 column. Radiochemical purity was determined by thin layer chromatography using Cellulose sheets and pyridine: ethanol: water (1: 2: 4) mixture as solvent. The {sup 153}Sm-EDTMP has been shown to be stable for two weeks. Three particulate preparations of {sup 153}Sm used for the irradiation of chronic synovitis have been studied. They are hydroxyapatite particles, human serum albumin microspheres and ferric hydroxide macroaggregates. The {sup 153}Sm-ferric hydroxide macroaggregates were prepared in a single step by coprecipitation of {sup 153}Sm in the formation of Fe(OH){sub 3}. Preparation of {sup 153}Sm-labelled hydroxyapatite particles and {sup 153}Sm-labelled albumin microspheres were carried out by {sup 153}Sm labelling of previously prepared particles. Radiolabelling efficiency were greater than 95% for hydroxyapatite particles and macroaggregates and was lower than 20% for albumin microspheres. The particle sizes were inspected using an optical microscope with a haemocytometer and micrometric ocular. (author)

  6. Recent applications of nuclear medicine in diagnostics (I part

    Directory of Open Access Journals (Sweden)

    Giorgio Treglia

    2013-04-01

    Full Text Available Introduction: Aim of this review is to describe the recent applications of nuclear medicine techniques in diagnostics, particularly in oncology. Materials and methods: We reviewed scientific literature data searching for the current role of tomographic nuclear medicine techniques (SPECTand PET in oncology and summarized the main applications of these techniques. Results: Nuclear medicine techniques have a key role in oncology allowing early diagnosis of many tumours, an accurate staging of disease and evalutation of treatment response. Hybrid SPECT/CT and PET/CT imaging systems now provide metabolic and functional information from SPECTor PETcombined with the high spatial resolution and anatomic information of CT. The most frequent applications of SPECT/CT in oncology concern thyroid tumours, neuroendocrine tumours, bone metastases and lymph node mapping. Furthermore the evaluation of many tumours may benefit from PET/CT imaging. Discussion: The recent development of new radiopharmaceuticals and the growth of hybrid tomographic devices, such as SPECT/CT and PET/CT, now permits molecular imaging of biologic processes at the cellular level to improve both the diagnosis and treatment of many tumours.

  7. Identificação do linfonodo sentinela no câncer de mama com injeção subdérmica periareolar em quatro pontos do radiofármaco Sentinel lymph node identification in breast cancer using periareolar and subdermal injection of the radiopharmaceutical in four points

    Directory of Open Access Journals (Sweden)

    Afrânio Coelho-Oliveira

    2004-08-01

    Full Text Available Este estudo visa identificar o linfonodo sentinela por meio da injeção exclusiva de radiofármaco periareolar subdérmico em quatro pontos, independente da topografia do tumor. A biópsia do linfonodo sentinela diminui a morbidade no estadiamento da axila. Foram realizadas 57 biópsias do linfonodo sentinela, em pacientes com câncer de mama, prospectivamente, em dois grupos: grupo A (25 pacientes e grupo B (32 pacientes. Realizamos a injeção do radiofármaco peritumoral no grupo A, e nova técnica periareolar em quatro pontos no grupo B. A biópsia do linfonodo sentinela foi estudada por "imprint" citológico e hematoxilina e eosina, seguida de linfadenectomia axilar no grupo A e nos casos positivos do grupo B. No grupo A foram identificados 88% (22/25 de linfonodos sentinelas, não houve falso-negativo, com sensibilidade e especificidade de 100%; no grupo B foram identificados 96% (31/32 de linfonodos sentinelas e valor preditivo positivo de 100%. O número de linfonodos sentinelas variou de 1 a 7, moda de 1 e média de 2,7, a área de maior captação variou de 10 a 100 vezes. A injeção periareolar em quatro pontos se apresenta como bom método no mapeamento linfático para identificação do linfonodo sentinela. A padronização deste sítio pode ser o de escolha para identificação do linfonodo sentinela, sendo necessário maior número de casos para confirmação destes achados.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 hematoxilin and eosin staining

  8. Design Concepts in Set Parts Supply Implementation

    Directory of Open Access Journals (Sweden)

    Suhartini Mohd Jainury

    2013-10-01

    Full Text Available The increasing number of parts variants on an assembly line requires an improvement for a cost efficient and flexible parts supply system. For that reason, the Set Parts Supply (SPS system was introduced by Toyota as a new material handling system for supplying parts in sets based on the kitting concept. In this study, we investigate the consideration of design concepts in SPS implementation at one of Malaysia’s automotive manufacturers through a case study in a mixed-model assembly line that contains many parts to be assembled to the car body. From our case study, we found that the design of the ‘parts only’ or minomi concept on the component racks contributes to the elimination of waste; mura, muri and muda. Finally, we present the lean approach in the minomi concepts that used in designing the component racks.

  9. Neuroscience in Nazi Europe Part III

    DEFF Research Database (Denmark)

    Zeidman, Lawrence A; Kondziella, Daniel

    2012-01-01

    In Part I, neuroscience collaborators with the Nazis were discussed, and in Part II, neuroscience resistors were discussed. In Part III, we discuss the tragedy regarding european neuroscientists who became victims of the Nazi onslaught on “non-Aryan” doctors. Some of these unfortunate neuroscient...... of neuroscience, we pay homage and do not allow humanity to forget, lest this dark period in history ever repeat itself....

  10. Machining Thin-Walled Cylindrical Parts

    Science.gov (United States)

    Cimbak, Joe; Spagnolo, Jim; Kraus, Dan

    1988-01-01

    Cylindrical walls only few thousandths of inch thick machined accurately and without tears or punctures with aid of beryllium copper mandrel. Chilled so it contracts, then inserted in cylinder. As comes to room temperature, mandrel expands and fits snugly inside cylinder. Will not allow part to slide and provides solid backup to prevent deflection when part machined by grinding wheel. When machining finished, cylinder-and-mandrel assembly inserted in dry ice, mandrel contracts and removed from part.

  11. Reliability and quality EEE parts issues

    Science.gov (United States)

    Barney, Dan; Feigenbaum, Irwin

    1990-01-01

    NASA policy and procedures are established which govern the selection, testing, and application of electrical, electronic, and electromechanical (EEE) parts. Recent advances in the state-of-the-art of electronic parts and associated technologies can significantly impact the electronic designs and reliability of NASA space transportation avionics. Significant issues that result from these advances are examined, including: recent advances in microelectronics technology (as applied to or considered for use in NASA projects); electron packaging technology advances (concurrent with, and as a result of, the development of the advanced microelectronic devices); availability of parts used in space avionics; and standardization and integration of parts activities between projects, centers, and contractors.

  12. Research on Part Experssion Methodology of Part Library Based on ISO13584

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    ISO13584 (PLIB) is an international standard, which is established to realize computer's identification ofdata expression and data exchange of part library. In this international standard, part expression methodology ofpart library is an important characteristic, which distinguishes itself from STEP. So, the methodology is a focus inthe research of part library. This article describes the principles of part information expression of part library basedon ISO13584, and the research results of the methodology in details.

  13. Metrology of Large Parts. Chapter 5

    Science.gov (United States)

    Stahl, H. Philip

    2012-01-01

    As discussed in the first chapter of this book, there are many different methods to measure a part using optical technology. Chapter 2 discussed the use of machine vision to measure macroscopic features such as length and position, which was extended to the use of interferometry as a linear measurement tool in chapter 3, and laser or other trackers to find the relation of key points on large parts in chapter 4. This chapter looks at measuring large parts to optical tolerances in the sub-micron range using interferometry, ranging, and optical tools discussed in the previous chapters. The purpose of this chapter is not to discuss specific metrology tools (such as interferometers or gauges), but to describe a systems engineering approach to testing large parts. Issues such as material warpage and temperature drifts that may be insignificant when measuring a part to micron levels under a microscope, as will be discussed in later chapters, can prove to be very important when making the same measurement over a larger part. In this chapter, we will define a set of guiding principles for successfully overcoming these challenges and illustrate the application of these principles with real world examples. While these examples are drawn from specific large optical testing applications, they inform the problems associated with testing any large part to optical tolerances. Manufacturing today relies on micrometer level part performance. Fields such as energy and transportation are demanding higher tolerances to provide increased efficiencies and fuel savings. By looking at how the optics industry approaches sub-micrometer metrology, one can gain a better understanding of the metrology challenges for any larger part specified to micrometer tolerances. Testing large parts, whether optical components or precision structures, to optical tolerances is just like testing small parts, only harder. Identical with what one does for small parts, a metrologist tests large parts and optics

  14. The Search for Another Earth - Part II

    Indian Academy of Sciences (India)

    2016-10-01

    In the first part, we discussed the various methods for thedetection of planets outside the solar system known as theexoplanets. In this part, we will describe various kinds ofexoplanets. The habitable planets discovered so far and thepresent status of our search for a habitable planet similar tothe Earth will also be discussed.

  15. Reproduce and die! Why aging? Part II

    NARCIS (Netherlands)

    Schuiling, GA

    2005-01-01

    Whilst in part I of this diptych on aging the question why aging exists at all is discussed; this part deals with the question which mechanisms underly aging and, ultimately, dying. It appears that aging is not just an active process as such - although all kinds of internal (e.g., oxigen-free radica

  16. Search Engines for Tomorrow's Scholars, Part Two

    Science.gov (United States)

    Fagan, Jody Condit

    2012-01-01

    This two-part article considers how well some of today's search tools support scholars' work. The first part of the article reviewed Google Scholar and Microsoft Academic Search using a modified version of Carole L. Palmer, Lauren C. Teffeau, and Carrier M. Pirmann's framework (2009). Microsoft Academic Search is a strong contender when…

  17. Part Time Study in Higher Education.

    Science.gov (United States)

    Neville, Colin

    This document, which is intended for adults considering enrolling in part-time study in higher education, examines the objectives and experiences of adults who have pursued part-time study in higher education in the United Kingdom. The following reasons why adults return to higher education are discussed: personal development; self-fulfillment;…

  18. Recurring part arrangements in shape collections

    KAUST Repository

    Zheng, Youyi

    2014-05-01

    Extracting semantically related parts across models remains challenging, especially without supervision. The common approach is to co-analyze a model collection, while assuming the existence of descriptive geometric features that can directly identify related parts. In the presence of large shape variations, common geometric features, however, are no longer sufficiently descriptive. In this paper, we explore an indirect top-down approach, where instead of part geometry, part arrangements extracted from each model are compared. The key observation is that while a direct comparison of part geometry can be ambiguous, part arrangements, being higher level structures, remain consistent, and hence can be used to discover latent commonalities among semantically related shapes. We show that our indirect analysis leads to the detection of recurring arrangements of parts, which are otherwise difficult to discover in a direct unsupervised setting. We evaluate our algorithm on ground truth datasets and report advantages over geometric similarity-based bottom-up co-segmentation algorithms. © 2014 The Author(s) Computer Graphics Forum © 2014 The Eurographics Association and John Wiley & Sons Ltd. Published by John Wiley & Sons Ltd.

  19. Spatial part-set cuing facilitation.

    Science.gov (United States)

    Kelley, Matthew R; Parasiuk, Yuri; Salgado-Benz, Jennifer; Crocco, Megan

    2016-07-01

    Cole, Reysen, and Kelley [2013. Part-set cuing facilitation for spatial information. Journal of Experimental Psychology: Learning, Memory, & Cognition, 39, 1615-1620] reported robust part-set cuing facilitation for spatial information using snap circuits (a colour-coded electronics kit designed for children to create rudimentary circuit boards). In contrast, Drinkwater, Dagnall, and Parker [2006. Effects of part-set cuing on experienced and novice chess players' reconstruction of a typical chess midgame position. Perceptual and Motor Skills, 102(3), 645-653] and Watkins, Schwartz, and Lane [1984. Does part-set cuing test for memory organization? Evidence from reconstructions of chess positions. Canadian Journal of Psychology/Revue Canadienne de Psychologie, 38(3), 498-503] showed no influence of part-set cuing for spatial information when using chess boards. One key difference between the two procedures was that the snap circuit stimuli were explicitly connected to one another, whereas chess pieces were not. Two experiments examined the effects of connection type (connected vs. unconnected) and cue type (cued vs. uncued) on memory for spatial information. Using chess boards (Experiment 1) and snap circuits (Experiment 2), part-set cuing facilitation only occurred when the stimuli were explicitly connected; there was no influence of cuing with unconnected stimuli. These results are potentially consistent with the retrieval strategy disruption hypothesis, as well as the two- and three-mechanism accounts of part-set cuing.

  20. CRACK REASON ANALYSIS OF DAMAGED CARBONITRIDED PART

    Directory of Open Access Journals (Sweden)

    Karin Kocúrová

    2010-03-01

    Full Text Available The article deals with the analysis of a damaged part, which was designed for use in a mechanical clutch of a car. The crack in the part was found during the production inspection. The aim of metallographic and fractography analyses of the fracture surfaces was to discover the reasons for the crack. The reason for creating the crack was the formation of smaller cracks in the production during pressing process of the semiproduct. These cracks even grew after the following thermochemical treatment. The fracture was initiated during the straightening process of quenched part.

  1. A Universal Part-of-Speech Tagset

    CERN Document Server

    Petrov, Slav; McDonald, Ryan

    2011-01-01

    To facilitate future research in unsupervised induction of syntactic structure and to standardize best-practices, we propose a tagset that consists of twelve universal part-of-speech categories. In addition to the tagset, we develop a mapping from 25 different treebank tagsets to this universal set. As a result, when combined with the original treebank data, this universal tagset and mapping produce a dataset consisting of common parts-of-speech for 22 different languages. We highlight the use of this resource via two experiments, including one that reports competitive accuracies for unsupervised grammar induction without gold standard part-of-speech tags.

  2. Concurrent Process Planning for Machined Parts

    Institute of Scientific and Technical Information of China (English)

    吴丹; 王先逵; 李志忠

    2002-01-01

    Detailed manufacturing information about the parts can help designers produce better designs. Detailed manufacturing information is conveyed to the designer through micro-circles within the concurrent design process for machined parts, focusing on instantaneous product design and process planning. The process has three key elements: a hierarchical architecture design of the concurrent process planning system, modeling and reengineering of the concurrent process planning, and modeling of information. The approach is successfully implemented and applied for concurrent design and process planning of some complicated parts.

  3. 49 CFR 236.505 - Proper operative relation between parts along roadway and parts on locomotive.

    Science.gov (United States)

    2010-10-01

    ... roadway and parts on locomotive. 236.505 Section 236.505 Transportation Other Regulations Relating to... SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards § 236.505 Proper operative relation between parts along roadway and parts on locomotive....

  4. The Use and Abuse of Part-Time Faculty: The Part-Timers' Point of View.

    Science.gov (United States)

    Wilson, Wendy L.

    Problems faced by part-time faculty members are identified, and suggestions to avoid mistreatment of these teachers are offered. Disadvantages of part-time teaching include the lack of equitable pay and benefits. Since most institutions have a standard pay rate for part-timers, it is suggested that teaching excellence be recognized by creating…

  5. 45 CFR Appendix A to Part 1110 - Federal Financial Assistance to Which This Part Applies

    Science.gov (United States)

    2010-10-01

    ... research in the humanities. 5. Support of educational programs in the humanities, including the training of... Applies A Appendix A to Part 1110 Public Welfare Regulations Relating to Public Welfare (Continued... Pt. 1110, App. A Appendix A to Part 1110—Federal Financial Assistance to Which This Part Applies...

  6. 22 CFR Appendix A to Part 141 - Federal Financial Assistance to Which This Part Applies

    Science.gov (United States)

    2010-04-01

    ... and cultural exchange—studies, research, instruction and other educational activities—cultural... Applies A Appendix A to Part 141 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS NONDISCRIMINATION IN... 1964 Pt. 141, App. A Appendix A to Part 141—Federal Financial Assistance to Which This Part Applies...

  7. Medicare Provider Data - Part D Prescriber

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Part D Prescriber Public Use File (PUF) provides information on prescription drugs prescribed by individual physicians and other health care providers and paid...

  8. Langevarjurid ja Pekingi part / Kaarel Kressa

    Index Scriptorium Estoniae

    Kressa, Kaarel, 1983-

    2010-01-01

    Kahest lühifilmist, mis linastusid 14. detsembril kinos Sõprus. Mihkel Soe dokumentaalfilmist ekstreemsportlasest Toomas Taltsist "3. 2. 1 - ilus hüpe" ja Kristin Kalamehe lühikomöödiast "Pekingi part"

  9. Smart variations: Functional substructures for part compatibility

    KAUST Repository

    Zheng, Youyi

    2013-05-01

    As collections of 3D models continue to grow, reusing model parts allows generation of novel model variations. Naïvely swapping parts across models, however, leads to implausible results, especially when mixing parts across different model families. Hence, the user has to manually ensure that the final model remains functionally valid. We claim that certain symmetric functional arrangements (sFarr-s), which are special arrangements among symmetrically related substructures, bear close relation to object functions. Hence, we propose a purely geometric approach based on such substructures to match, replace, and position triplets of parts to create non-trivial, yet functionally plausible, model variations. We demonstrate that starting even from a small set of models such a simple geometric approach can produce a diverse set of non-trivial and plausible model variations. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  10. Medicare Part D Opioid Drug Mapping Tool

    Data.gov (United States)

    U.S. Department of Health & Human Services — The opioid prescribing rate interactive mapping tool shows geographic comparisons, at the state, county, and ZIP code levels, of de-identified Medicare Part D opioid...

  11. Labor law update--Part 1.

    Science.gov (United States)

    Fiesta, J

    1997-01-01

    To ensure proper actions when making managerial decisions, nurses must be aware of labor laws and the policies that apply to them. Part 1 of "Labor Law Update" discusses public policy considerations and gender, racial and pregnancy discrimination.

  12. Labor law update--Part 4.

    Science.gov (United States)

    Fiesta, J

    1997-09-01

    Many hospitals are eliminating positions as part of the restructuring process. If these decisions involve race, nationality, age or gender discrimination, back pay and punitive damages may be awarded. Cases involving wrongful termination issues are discussed.

  13. Manganese ferrite thin films Part II: Properties

    NARCIS (Netherlands)

    Hulscher, W.S.

    1972-01-01

    Some properties of evaporated manganese ferrite thin films are investigated, e.g. resistivity, magnetization reversal, Curie temperature, Faraday rotation and optical absorption. The properties are partly related to the partial oxygen pressure present during a preceding annealing process.

  14. Periodontal Disease Part IV: Periodontal Infections

    OpenAIRE

    Turnbull, Robert S.

    1988-01-01

    In Part IV of this article, the author describes two periodontal infections, acute necrotizing ulcerative gingivitis (trench mouth) and periodontal abscess, both acute painful conditions for which patients may seek advice from their family physician rather than their dentist.

  15. Medicare Part D Prescriber Interactive Dataset

    Data.gov (United States)

    U.S. Department of Health & Human Services — As part of the Obama Administrations efforts to make our healthcare system more transparent, affordable, and accountable, the Centers for Medicare and Medicaid...

  16. Rapid Prototyping Of Layered Composite Parts

    Science.gov (United States)

    Wolff, Edwin D.

    1992-01-01

    Numerically controlled cutting accelerates fabrication of layers. Proposed method derived from stereoscopic lithography. CATIA or CAEDS computer program used to generate three-dimensional mathematical model of prototype part. In model, geometry of part specified in layers, as in stereoscopic lithography. Model data for each layer fed to computer-numerically-controlled ultrasonic cutting machine. Sheet of prepreg (uncured composite material) of specified layer thickness placed in machine and cut, under control of model data, to specified shape of layer.

  17. Social security and part-time employment.

    Science.gov (United States)

    Euzeby, A

    1988-01-01

    "The author examines social security provisions that constitute obstacles to part-time employment before considering a number of measures that could be taken to make the schemes more flexible and hence promote part-time employment both as a means of meeting the needs of many workers and as a form of work sharing that can help to combat unemployment." The geographical focus is on developed countries, with an emphasis on Europe.

  18. DISCRETIZATION APPROACH USING RAY-TESTING MODEL IN PARTING LINE AND PARTING SURFACE GENERATION

    Institute of Scientific and Technical Information of China (English)

    HAN Jianwen; JIAN Bin; YAN Guangrong; LEI Yi

    2007-01-01

    Surface classification, 3D parting line, parting surface generation and demoldability analysis which is helpful to select optimal parting direction and optimal parting line are involved in automatic cavity design based on the ray-testing model. A new ray-testing approach is presented to classify the part surfaces to core/cavity surfaces and undercut surfaces by automatic identifying the visibility of surfaces. A simple, direct and efficient algorithm to identify surface visibility is developed. The algorithm is robust and adapted to rather complicated geometry, so it is valuable in computer-aided mold design systems. To validate the efficiency of the approach, an experimental program is implemented. Case studies show that the approach is practical and valuable in automatic parting line and parting surface generation.

  19. Living musical instruments and inanimate body parts?

    Science.gov (United States)

    Barbarotto, R; Capitani, E; Laiacona, M

    2001-01-01

    In the literature about category effects in semantic memory, body parts and musical instruments are often considered atypical, because in cases with a disproportionate impairment of living categories body parts are relatively spared, while musical instruments are often severely defective. In this study the performance of 57 subjects affected by diseases generally associated with lexical-semantic impairment, for the most part Alzheimer's disease and other forms of cortical degeneration, but also herpetic encephalitis and traumatic brain damage are analyzed. The subjects were given a picture naming task tapping eight categories: three living categories (animals, fruits and vegetables) and three non-living categories (tools, furniture and vehicles), plus body parts and musical instruments. On a preliminary analysis at the group level, body parts were the least impaired category and musical instruments the most severely impaired, the six living and non-living categories being intermediate. However, these differences disappeared after covariance for lexical frequency, name agreement and age of acquisition. The relationship between living categories, non-living categories, musical instruments and body parts was investigated by means of a Lisrel model of Confirmatory Factor Analysis. Two latent variables related to living and non-living categories respectively were defined, and it was found that both body parts and musical instruments were significantly related only with non-living categories. The results showed that the definition of the latent variable expressing the substrate of non-living categories was less satisfactory than that expressing the living categories. On this basis, the conclusions of this study appear statistically definite but their psychological interpretation is less straightforward.

  20. Comparison beta absorbed dose from 203Hg, 166Ho and 177LU isotopes in cortex and medulla in tree part kidney and integrated kidney using Monte Carlo method

    Directory of Open Access Journals (Sweden)

    Mohammad Mirzaei

    2015-04-01

    Full Text Available Background: Large quantities of radiopharmaceuticals prescribed for treatment and diagnosis are excreted through kidney. Therefore, radiation unwanted dose is created in kidney. As a result, exact calculation of prescribed medicine amount is important. In Mird pamphlet, 5 kidneys have considered in ellipsoidal shape that radiopharmaceutical is uniform distributed in them and gamma absorption fraction is calculated and recorded in the tables and the fraction of beta absorption is considered unit. While, kidney has internal organs and radioisotope is not uniform distributed in and beta absorbed fraction is not unit. Material and method: In this research, for the first time kidney is considered integrated shape and for the second time has been considered that it is consisted of three areas, pelvis, medulla and cortex. It is supposed that radiopharmaceutical is distributed in medulla. Then, beta absorbed dose is calculated in medulla and cortex using MCNPX code and is compared with integrated kidney results. Resuts: This research has been showed that beta absorbed dose from 203Hg, 166Ho and 177Lu isotopes in medulla is four times as much as dose in integrated kidney and beta dose in cortex is 0.004 to 0.012 times as much as beta dose in integrated kidney. Conclusion: Internal structure of kidney should be considered in simulation to achieve a more accurate prescribed dose. It is recommended that simulation results of three areas kidney are replaced with integrated kidney to prevent from renal toxicity.