Kinetic studies on the hafnium nad deuterium

International Nuclear Information System (INIS)

Bing Wenzeng; Long Xinggui; Zhu Zuliang

2009-04-01

Through the method of reaction rate analysis in a constant volume reactor, the time dependence of the pressure drop of the hafnium deuteride formation are studied over a temperature range 573-873 K on a metal hydride thermodynamic and kinetic parameters measuring apparatus. The rate constants of the hafnium deuteride formation, which are 0.0530 s -1 , 0.0452 s -1 , 0.0319 s -1 , 0.0261 s -1 , are calculated at a serial temperatures of 573 K, 673 K, 773 K, 873 K and the initial pressure of 13 kPa. The activation energy of the reaction is (-10.1±1.5) kJ·mol -1 . Comparing the above results with those of titanium deuteride formation on the same measuring apparatus, the kinetic mechanism of the deuteride formation of hafnium and titanium is considered different. It is concluded that the reaction rate of hafnium absorbing deuterium may be controlled by phase transformation and surface oxidation. (authors)

Electronic properties of hafnium oxide: A contribution from defects and traps

Energy Technology Data Exchange (ETDEWEB)

Gritsenko, Vladimir A., E-mail: grits@isp.nsc.ru; Perevalov, Timofey V.; Islamov, Damir R., E-mail: damir@isp.nsc.ru

2016-02-15

In the present article, we give a review of modern data and latest achievements pertaining to the study of electronic properties of oxygen vacancies in hafnium oxide. Hafnium oxide is a key dielectric for use in many advanced silicon devices. Oxygen vacancies in hafnium oxide largely determine the electronic properties of the material. We show that the electronic transitions between the states due to oxygen vacancies largely determine the optical absorption and luminescent properties of hafnium oxide. We discuss the role of oxygen vacancies as traps that facilitate charge transport in hafnium oxide films. Also, we demonstrate the fact that the electrical conductivity in hafnium oxide is controlled by the phonon-assisted tunnelling of charge carriers between traps that were identified as oxygen vacancies.

Preparation of complexes of zirconium and hafnium tetrachlorides with phosphorus oxychloride

International Nuclear Information System (INIS)

McLaughlin, D.F.

1989-01-01

This patent describes an improvement in a method for separating hafnium tetrachloride from zirconium tetrachloride where a complex of zirconium-hafnium tetrachlorides and phosphorus oxychloride is prepared from zirconium-hafnium tetrachlorides and the complex of zirconium-hafnium tetrachlorides and phosphorus oxychloride is introduced into a distillation column, which distillation column has a reboiler connected at the bottom and a reflux condenser connected at the top and where a hafnium tetrachloride enriched stream is taken from the top of the column and a zirconium enriched tetrachloride stream is taken from the bottom of the column. The improvement comprising: prepurifying the zirconium-hafnium tetrachlorides, prior to preparation of the complex and introduction of the complex into a distillation column, to substantially eliminate iron chloride from the zirconium hafnium tetrachlorides, whereby buildup or iron chloride in the distillation column and in the reboiler is substantially eliminated and the column can be operated in a continuous, stable and efficient manner

Correlations between nuclear data and results of integral slab experiments. Case of hafnium; Correlations entre donnees nucleaires et experiences integrales a plaques: le cas du hafnium

Energy Technology Data Exchange (ETDEWEB)

Palau, J M

1997-10-22

The aim of this thesis was to evaluate how much integral slab experiments can both reduce discrepancies between experimental results and calculations, and improve the knowledge of hafnium isotopes neutronic parameters by an adapted sensitivity and uncertainty method. A statistical approach, based on the generalized least squares method and perturbation theory, has been incorporated into our calculation system in order to deduce microscopic cross-section adjustments from observed integral measurements on this particular `mock-up` reactor. In this study it has been established that the correlations between integral parameters and hafnium capture cross-sections enable specific variations in the region of resolved resonances at the level of multigroup and punctual cross-sections recommended data (JEF-2.2 evaluation) to be highlighted. The use of determinist methods (APOLLO2 code) together with Monte Carlo- type simulations (TRIPOLI4 code) enabled a depth analysis of the modelling approximations to be carried out. Furthermore, the sensitivity coefficient validation technique employed leads to a reliable assessment of the quality of the new basic nuclear data. In this instance, the adjustments proposed for certain isotope {sup 177}Hf resonance parameters reduce, after error propagation, by 3 to 5 per cent the difference between experimental results and calculations related to this absorbent`s efficiency. Beyond this particular application, the qualification methodology integrated in our calculation system should enable other basic sizing parameters to be treated (chemical / geometric data or other unexplored nuclear data) to make technological requirements less stringent. (author) 128 refs.

Study of fine structure of deformed hafnium

International Nuclear Information System (INIS)

Voskresenskaya, L.A.; Petukhova, A.S.; Kovalev, K.S.

1978-01-01

Variations in the hafnium fine structure following the cold plastic deformation have been studied. The fine structure condition has been studied through the harmonic analysis of the profile of the X-ray diffraction line, obtained at the DRON-I installation. Received has been the dependence of the crystal lattice microdistortions value on the deformation extent for hafnium. This dependence is compared with the corresponding one for zirconium. It is found out that at all the deformations the microdistortion distribution is uniform. The microdistortion value grows with the increase in the compression. During the mechanical impact higher microdistortions of the crystal lattice occur in the hafnium rather than in zirconium

Properties of filmogen solutions and films of hafnium compounds

International Nuclear Information System (INIS)

Sviridova, A.I.

1986-01-01

Study on hafnium hydrolizing compound solutions, used for hafnium oxide homogeneous layer formation, is conducted. In particular, electric conductivity, acidity and refractive index were investigated depending on the sal on ether concentration and the storage time. Oxyhafnium nitrate, hafnium chloride in ethanol, dichlorodiethoxyhafnium, hafnium oxychloride were used as initial compounds. Hydrolysis of hafnium compounds in solution occurs partially; further process occurs in the thin layer on the optical element surface; final decomposition is performed under heat treatment. It is ascertained, that alcoholic-aqueous solutions of inorganic salts can be filmogen only at definite acidity, density and viscosity (1.33-2.5 cp.). It is also ascertained that refractive index values and transmission spectral boundary of coatings, produced from alkoxy compound solutions and from chloride salt solutions, are practically the same. Transmittance boundary in ultraviolet region of spectrum of oxide films produced from nitrate and chloride solutions, varies with the heating temperature increase differently

Investigation of ferromagnetism in oxygen deficient hafnium oxide thin films

Energy Technology Data Exchange (ETDEWEB)

Hildebrandt, Erwin; Kurian, Jose; Krockenberger, Yoshiharu; Alff, Lambert [Institut fuer Materialwissenschaft, TU Darmstadt (Germany); Suter, Andreas [PSI, Villingen (Switzerland); Wilhelm, Fabrice; Rogalev, Andrei [ESRF, Grenoble (France)

2008-07-01

Oxygen deficient thin films of hafnium oxide were grown on single crystal r-cut and c-cut sapphire by reactive molecular beam epitaxy. RF-activated oxygen was used for the in situ oxidation of hafnium oxide thin films. Oxidation conditions were varied substantially in order to create oxygen deficiency in hafnium oxide films intentionally. The films were characterized by X-ray and magnetic measurements. X-ray diffraction studies show an increase in lattice parameter with increasing oxygen deficiency. Oxygen deficient hafnium oxide thin films also showed a decreasing bandgap with increase in oxygen deficiency. The magnetisation studies carried out with SQUID did not show any sign of ferromagnetism in the whole oxygen deficiency range. X-ray magnetic circular dichroism measurements also confirmed the absence of ferromagnetism in oxygen deficient hafnium oxide thin films.

Titanium zirconium and hafnium coordination compounds with vanillin thiosemicarbazone

International Nuclear Information System (INIS)

Konunova, Ts.B.; Kudritskaya, S.A.

1987-01-01

Coordination compounds of titanium zirconium and hafnium tetrachlorides with vanillin thiosemicarbazone of MCl 4 x nLig composition, where n=1.5, 4 for titanium and 1, 2, 4 for zirconium and hafnium, are synthesized. Molar conductivity of ethanol solutions is measured; IR spectroscopic and thermochemical investigation are carried out. The supposition about ligand coordination via sulfur and azomethine nitrogen atoms is made. In all cases hafnium forms stable compounds than zirconium

Hafnium - material for chemical apparatus engineering

International Nuclear Information System (INIS)

Jennert, D.

1981-01-01

This work describes - on the background of available literature - the properties of hafnium in technical quality (DIN-material No. 2.6400) as material for chemical apparatus engineering. The occurence, refining, physical and chemical properties will be described as well as the material behavior. In conclusion, it has been found that there is, at present, sufficient information for the engineering of hafnium which has to be completed by additional investigations for special applications. (orig.) [de

Internal Dosimetry for Inhalation of Hafnium Tritide Aerosols

Energy Technology Data Exchange (ETDEWEB)

Inkret, W.C.T.; Schillaci, M.E.; Boyce, M.K.; Cheng, Y.S.; Efurd, D.W.; Little, T.T.; Miller, G.; Musgrave, J.A.; Wermer, J.R

2001-07-01

Metal tritides with low dissolution rates may have residence times in the lungs which are considerably longer than the biological half-time normally associated with tritium in body water, resulting in long-term irradiation of the lungs by low energy {beta} particles and bremsstrahlung X rays. Samples of hafnium tritide were placed in a lung simulant fluid to determine approximate lung dissolution rates. Hafnium hydride samples were analysed for particle size distribution with a scanning electron microscope. Lung simulant data indicated a biological dissolution half-time for hafnium tritide on the order of 10{sup 5}d. Hafnium hydride particle sizes ranged between 2 and 10 {mu}m, corresponding to activity median aerodynamic diameters of 5 to 25 {mu}m. Review of in vitro dissolution data, development of a biokinetic model, and determination of secondary limits for 1 {mu}m AMAD particles are presented and discussed. (author)

Correlations between nuclear data and integral slab experiments: the case of hafnium

International Nuclear Information System (INIS)

Palau, J.M.

1999-01-01

The aim of this work was to evaluate how much integral slab experiments can both reduce discrepancies between experimental results and calculations, and improve the knowledge of hafnium isotopes neutronic parameters by an adapted sensitivity and uncertainty method. A statistical approach, based on the generalized least squares method and perturbation theory, has been incorporated into our calculation system in order to deduce microscopic cross-section adjustments from observed integral measurements on this particular 'mock-up' reactor.In this study it has been established that the correlations between integral parameters and hafnium capture cross-sections enable specific variations in the region of resolved resonances at the level of multigroup and punctual cross-sections recommended data (JEF-2.2 evaluation) to be highlighted. The use of determinist methods together with Monte Carlo- type simulations enabled a depth analysis of the modelling approximations to be carried out. Furthermore, the sensitivity coefficient validation technique employed leads to a reliable assessment of the quality of the new basic nuclear data. In this instance, the adjustments proposed for certain isotope 177 Hf resonance parameters reduce, after error propagation, by 3 to 5 per cent the difference between experimental results and calculations related to this absorbent's efficiency. Beyond this particular application, the qualification methodology integrated in our calculation system should enable other basic sizing parameters to be treated (chemical / geometric data or other unexplored nuclear data) to make technological requirements less stringent. (author)

Titanium(IV), zirconium, hafnium and thorium

International Nuclear Information System (INIS)

Brown, Paul L.; Ekberg, Christian

2016-01-01

Titanium can exist in solution in a number of oxidation states. The titanium(IV) exists in acidic solutions as the oxo-cation, TiO 2+ , rather than Ti 4+ . Zirconium is used in the ceramics industry and in nuclear industry as a cladding material in reactors where its reactivity towards hydrolysis reactions and precipitation of oxides may result in degradation of the cladding. In nature, hafnium is found together with zirconium and as a consequence of the contraction in ionic radii that occurs due to the 4f -electron shell, the ionic radius of hafnium is almost identical to that of zirconium. All isotopes of thorium are radioactive and, as a consequence of it being fertile, thorium is important in the nuclear fuel cycle. The polymeric hydrolysis species that have been reported for thorium are somewhat different to those identified for zirconium and hafnium, although thorium does form the Th 4 (OH) 8 8+ species.

Ferroelectricity in undoped hafnium oxide

International Nuclear Information System (INIS)

Polakowski, Patrick; Müller, Johannes

2015-01-01

We report the observation of ferroelectric characteristics in undoped hafnium oxide thin films in a thickness range of 4–20 nm. The undoped films were fabricated using atomic layer deposition (ALD) and embedded into titanium nitride based metal-insulator-metal (MIM) capacitors for electrical evaluation. Structural as well as electrical evidence for the appearance of a ferroelectric phase in pure hafnium oxide was collected with respect to film thickness and thermal budget applied during titanium nitride electrode formation. Using grazing incidence X-Ray diffraction (GIXRD) analysis, we observed an enhanced suppression of the monoclinic phase fraction in favor of an orthorhombic, potentially, ferroelectric phase with decreasing thickness/grain size and for a titanium nitride electrode formation below crystallization temperature. The electrical presence of ferroelectricity was confirmed using polarization measurements. A remanent polarization P r of up to 10 μC cm −2 as well as a read/write endurance of 1.6 × 10 5 cycles was measured for the pure oxide. The experimental results reported here strongly support the intrinsic nature of the ferroelectric phase in hafnium oxide and expand its applicability beyond the doped systems

Hafnium-Based Contrast Agents for X-ray Computed Tomography.

Science.gov (United States)

Berger, Markus; Bauser, Marcus; Frenzel, Thomas; Hilger, Christoph Stephan; Jost, Gregor; Lauria, Silvia; Morgenstern, Bernd; Neis, Christian; Pietsch, Hubertus; Sülzle, Detlev; Hegetschweiler, Kaspar

2017-05-15

Heavy-metal-based contrast agents (CAs) offer enhanced X-ray absorption for X-ray computed tomography (CT) compared to the currently used iodinated CAs. We report the discovery of new lanthanide and hafnium azainositol complexes and their optimization with respect to high water solubility and stability. Our efforts culminated in the synthesis of BAY-576, an uncharged hafnium complex with 3:2 stoichiometry and broken complex symmetry. The superior properties of this asymmetrically substituted hafnium CA were demonstrated by a CT angiography study in rabbits that revealed excellent signal contrast enhancement.

40 CFR 471.90 - Applicability; description of the zirconium-hafnium forming subcategory.

Science.gov (United States)

2010-07-01

... zirconium-hafnium forming subcategory. 471.90 Section 471.90 Protection of Environment ENVIRONMENTAL... POINT SOURCE CATEGORY Zirconium-Hafnium Forming Subcategory § 471.90 Applicability; description of the zirconium-hafnium forming subcategory. This subpart applies to discharges of pollutants to waters of the...

Calorimetric measurements on hafnium titanate

International Nuclear Information System (INIS)

Kandan, R.; Prabhakara Reddy, B.; Panneerselvam, G.; Nagarajan, K.

2012-01-01

Owing to its desirable nuclear and mechanical properties such as good absorption cross-section for thermal neutrons (105 barns), hafnium titanate (HfTiO 4 ) finds application as control rods for nuclear reactors. An accurate knowledge of the thermo physical properties of this material is necessary for design of control rod and for modeling its performance. Heat capacity is an important thermodynamic property that determines the temperature dependent variation of all other thermodynamic properties. Hence enthalpy increments of hafnium titanate (HfTiO 4 ) were measured in the temperature range 803-1663 K by employing the method of inverse drop calorimetry using high temperature differential calorimeter

Preparation of complexes of zirconium and hafnium tetrachlorides with phosphorus oxychloride

International Nuclear Information System (INIS)

Snyder, T.S.; Stoltz, R.A.

1989-01-01

This patent describes an improvement in a method for separating hafnium chloride from zirconium chloride using a distillation column, with a hafnium chloride enriched vapor stream taken from the top of the column and a zirconium enriched chloride stream taken from the bottom of the column. The improvement comprising: purifying the zirconium-hafnium chloride in a molten salt purification vessel prior to or after introduction into the distillation column to substantially eliminate iron chloride from the zirconium-hafnium chloride by at least periodically removing iron chloride from the molten salt purification vessel by electrochemically plating iron onto an electrode in the molten salt purification vessel. The molten salt in the molten salt purification vessel consisting essentially of a mixture of chlorides selected from the group consisting of alkali metals, alkaline earth metals, zirconium, hafnium, aluminum, manganese, and zinc

Method of purifying zirconium tetrachloride and hafnium tetrachloride in a vapor stream

International Nuclear Information System (INIS)

Snyder, T.S.; Stolz, R.A.

1992-01-01

This patent describes a method of purifying zirconium tetrachloride and hafnium tetrachloride in a vapor stream from a sand chlorinator in which the silicon and metals present in sand fed to the chlorinator are converted to chlorides at temperatures over about 800 degrees C. It comprises cooling a vapor stream from a sand chlorinator, the vapor stream containing principally silicon tetrachloride, zirconium tetrachloride, and hafnium tetrachloride contaminated with ferric chloride, to a temperature of from about 335 degrees C to about 600 degrees C; flowing the vapor stream through a gaseous diffusion separative barrier to produce a silicon tetrachloride-containing vapor stream concentrated in zirconium tetrachloride and hafnium tetrachloride and a silicon tetrachloride-containing vapor stream depleted in zirconium tetrachloride and hafnium tetrachloride; adsorbing the ferric chloride in the separative barrier; and recovering the silicon tetrachloride stream concentrated in zirconium tetrachloride and hafnium tetrachloride separately from the silicon tetrachloride stream depleted in zirconium tetrachloride and hafnium tetrachloride

Correlations between nuclear data and results of integral slab experiments. Case of hafnium

International Nuclear Information System (INIS)

Palau, J.M.

1997-01-01

The aim of this thesis was to evaluate how much integral slab experiments can both reduce discrepancies between experimental results and calculations, and improve the knowledge of hafnium isotopes neutronic parameters by an adapted sensitivity and uncertainty method. A statistical approach, based on the generalized least squares method and perturbation theory, has been incorporated into our calculation system in order to deduce microscopic cross-section adjustments from observed integral measurements on this particular 'mock-up' reactor. In this study it has been established that the correlations between integral parameters and hafnium capture cross-sections enable specific variations in the region of resolved resonances at the level of multigroup and punctual cross-sections recommended data (JEF-2.2 evaluation) to be highlighted. The use of determinist methods (APOLLO2 code) together with Monte Carlo- type simulations (TRIPOLI4 code) enabled a depth analysis of the modelling approximations to be carried out. Furthermore, the sensitivity coefficient validation technique employed leads to a reliable assessment of the quality of the new basic nuclear data. In this instance, the adjustments proposed for certain isotope 177 Hf resonance parameters reduce, after error propagation, by 3 to 5 per cent the difference between experimental results and calculations related to this absorbent's efficiency. Beyond this particular application, the qualification methodology integrated in our calculation system should enable other basic sizing parameters to be treated (chemical / geometric data or other unexplored nuclear data) to make technological requirements less stringent. (author)

Spectrofluorimetric determination of hafnium and zirconium with 3,7-dihydroxyflavone

Energy Technology Data Exchange (ETDEWEB)

Ito, Takushi; Suzuki, Osamu; Seuzuki, Tetsuo; Murata, Akira

1986-04-01

The absorptive and fluorescent characteristics of the hafnium and zirconium complexes of 3-hydroxyflavone and its 12 hydroxy and methoxy derivatives have been studied. The fluorescence of the 1:1 hafnium - 3,7-dihydroxyflavone complex (lambdasub(ex.)397 nm,lambdasub(em.) 465 nm) in 3 M hydrochloric acid has been used to determine 2-40 ng ml/sup -1/ of hafnium. The fluorescence of the 1:1 zirconium - 3,7-dihydroxyflavone complex (lambdasub(ex.) 395 nm, lambda sub(em.) 465 nm) at pH 2.0 in 0.02 M sulphate solution has been used to determine 2-40 ng ml/sup -1/ of zirconium. These methods are very sensitive and can be used for the simultaneous determination of hafnium and zirconium with an error of about 5%.

Molten salt extractive distillation process for zirconium-hafnium separation

International Nuclear Information System (INIS)

McLaughlin, D.F.; Stoltz, R.A.

1989-01-01

This patent describes an improvement in a process for zirconium-hafnium separation. It utilizes an extractive distillation column with a mixture of zirconium and hafnium tetrachlorides introduced into a distillation column having a top and bottom with hafnium enriched overheads taken from the top of the column and a molten salt solvent circulated through the column to provide a liquid phase, and with molten salt solvent containing zirconium chloride being taken from the bottom of the distillation column. The improvements comprising: utilizing a molten salt solvent consisting principally of lithium chloride and at least one of sodium, potassium, magnesium and calcium chlorides; stripping of the zirconium chloride taken from the bottom of the distillation column by electrochemically reducing zirconium from the molten salt solvent; and utilizing a pressurized reflux condenser on the top of the column to add the hafnium chloride enriched overheads to the molten salt solvent previously stripped of zirconium chloride

40 CFR 421.330 - Applicability: Description of the primary zirconium and hafnium subcategory.

Science.gov (United States)

2010-07-01

... primary zirconium and hafnium subcategory. 421.330 Section 421.330 Protection of Environment ENVIRONMENTAL... CATEGORY Primary Zirconium and Hafnium Subcategory § 421.330 Applicability: Description of the primary zirconium and hafnium subcategory. The provisions of this subpart are applicable to discharges resulting...

Design and fabrication of hafnium tube to control the power of the irradiation test fuel in HANARO

Energy Technology Data Exchange (ETDEWEB)

Kim, D. H.; Lee, C. B.; Kim, Y. M.; Yang, Y. S.; Jung, Y. H

2003-05-01

For the irradiation test at HANARO, non-instrumentation capsule was manufactured and hafnium tube was used to control LHGR of HANARO. Hafnium tube can control the irradiation condition of HANARO similar to that of commercial reactor. Hafnium tube thickness was determined by the LHGR calculated at OR-4 irradiation hole to be installed the non-instrumented capsule. To fabricate the hafnium tube with hafnium plate, the fabrication method was determined by using the hafnium mechanical properties. And the tensile strength of hafnium was confirmed by tensile test. This report is confirmed the LHGR control at the OR-4 and the Hafnium fabrication for in used which the AFPCAP non-instrumented irradiation capsule.

Use of X-ray fluorescence analysis for the determination of hafnium in zircalloys

International Nuclear Information System (INIS)

Sato, I.M.; Salvador, V.L.R.; Lordello, A.R.

1985-01-01

The determination of hafnium at trace levels (ppm) in the presence of zirconium by X-ray fluorescence technique is presented. The samples were prepared in the form of double-layer pellets, with boric acid as the binding material. The most sensitive first order line of hafnium HfLα (0.157 nm), which is used analyticaly, has approximately 67% overlapping with second order line of zirconium ZrKα 1 , (0.079 nm). As the excitation potencial of zirconium is larger than hafnium, the best condition was selected, so that the interference of zirconium intensity would not be significant in hafnium analytical line. The method allowed the determination of hafnium above 5.0 ppm (LLd = 1.5 ppm) with an accuracy of less than 10%. (Author) [pt

Use of hafnium in control bars of nuclear reactors

International Nuclear Information System (INIS)

Ramirez S, J.R.; Alonso V, G.

2003-01-01

Recently the use of hafnium as neutron absorber material in nuclear reactors has been reason of investigation by virtue of that this material has nuclear properties as to the neutrons absorption and structural that can prolong the useful life of the control mechanisms of the nuclear reactors. In this work some of those more significant hafnium properties are presented like nuclear material. Also there are presented calculations carried out with the HELIOS code for fuel cells of uranium oxide and of uranium and plutonium mixed oxides under controlled conditions with conventional bars of boron carbide and also with similar bars to which are substituted the absorbent material by metallic hafnium, the results are presented in this work. (Author)

The corrosion behavior of hafnium in high-temperature-water environments

Energy Technology Data Exchange (ETDEWEB)

Rishel, D.M.; Smee, J.D.; Kammenzind, B.F.

1999-10-01

The high-temperature-water corrosion performance of hafnium is evaluated. Corrosion kinetic data are used to develop correlations that are a function of time and temperature. The evaluation is based on corrosion tests conducted in out-of-pile autoclaves and in out-of-flux locations of the Advanced Test Reactor (ATR) at temperatures ranging from 288 to 360 C. Similar to the corrosion behavior of unalloyed zirconium, the high-temperature-water corrosion response of hafnium exhibits three corrosion regimes: pretransition, posttransition, and spalling. In the pretransition regime, cubic corrosion kinetics are exhibited, whereas in the posttransition regime, linear corrosion kinetics are exhibited. Because of the scatter in the spalling regime data, it is not reasonable to use a best fit of the data to describe spalling regime corrosion. Data also show that neutron irradiation does not alter the corrosion performance of hafnium. Finally, the data illustrate that the corrosion rate of hafnium is significantly less than that of Zircaloy-2 and Zircaloy-4.

Corrosion potentials of hafnium in molten alkaline-earth metal chlorides

International Nuclear Information System (INIS)

Kovalik, O.Yu.; Tkhaj, V.D.

2000-01-01

Corrosion potentials of hafnium in molten calcium, strontium and barium chlorides are measured and their temperature dependences are determined. It is stated that the corrosion potential of hafnium becomes more electropositive with an increase of the environment temperature. If the temperature is the same the potential shifts to the interval of more electronegative values in the row of CaCl 2 , SrCl 2 , BaCl 2 which corresponds to a lesser corrosion rate in environments positioned from left to right. the comparison of hafnium corrosion potentials with previously measured values for titanium and zirconium shows that a metal activity decrease results in a more electronegative corrosion potential [ru

Electronic structure of pentacene on hafnium studied by ultraviolet photoelectron spectroscopy

International Nuclear Information System (INIS)

Kang, Seong Jun; Yi, Yeon Jin; Kim, Chung Yi; Whang, Chung Nam

2005-01-01

The electronic structure of pentacene on hafnium, which is a low work function metal, was analyzed by using ultraviolet photoelectron spectroscopy. The energy level alignment was studied by using the onset of the highest occupied molecular orbital level and the shift of the vacuum level of the pentacene layer, which was deposited on a clean hafnium surface in a stepwise manner. The measured onset of the highest occupied molecular orbital energy level was 1.52 eV from the Fermi level of hafnium. The vacuum level was shifted 0.28 eV toward higher binding energy with additional pentacene layers, which means an interfacial dipole exists at the interface between pentacene and hafnium. We confirm that a small electron injection barrier can be achieved by inserting a low work function metal in a pentacene thin-film transistor.

Synthesis of Hafnium-Based Ceramic Materials for Ultra-High Temperature Aerospace Applications

Science.gov (United States)

Johnson, Sylvia; Feldman, Jay

2004-01-01

This project involved the synthesis of hafnium (Hf)-based ceramic powders and Hf-based precursor solutions that were suitable for preparation of Hf-based ceramics. The Hf-based ceramic materials of interest in this project were hafnium carbide (with nominal composition HE) and hafnium dioxide (HfO2). The materials were prepared at Georgia Institute of Technology and then supplied to research collaborators Dr. Sylvia Johnson and Dr. Jay Feldman) at NASA Ames Research Center.

Application of hafnium hydride control rod to large sodium cooled fast breeder reactor

Energy Technology Data Exchange (ETDEWEB)

Ikeda, Kazumi, E-mail: kazumi_ikeda@mfbr.mhi.co.jp [Mitsubishi FBR Systems, Inc., 34-17, Jingumae 2-Chome, Shibuya-ku, Tokyo 150-0001 (Japan); Moriwaki, Hiroyuki, E-mail: hiroyuki_moriwaki@mfbr.mhi.co.jp [Mitsubishi FBR Systems, Inc., 34-17, Jingumae 2-Chome, Shibuya-ku, Tokyo 150-0001 (Japan); Ohkubo, Yoshiyuki, E-mail: yoshiyuki_okubo@mfbr.mhi.co.jp [Mitsubishi FBR Systems, Inc., 34-17, Jingumae 2-Chome, Shibuya-ku, Tokyo 150-0001 (Japan); Iwasaki, Tomohiko, E-mail: tomohiko.iwasaki@qse.tohoku.ac.jp [Department of Quantum Science and Energy Engineering, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai-shi, Miyagi-ken 980-8579 (Japan); Konashi, Kenji, E-mail: konashi@imr.tohoku.ac.jp [Institute for Materials Research, Tohoku University, Narita-cho, Oarai-machi, Higashi-Ibaraki-gun, Ibaraki-ken 311-1313 (Japan)

2014-10-15

Highlights: • Application of hafnium hydride control rod to large sodium cooled fast breeder reactor. • This paper treats application of an innovative hafnium hydride control rod to a large sodium cooled fast breeder reactor. • Hydrogen absorption triples the reactivity worth by neutron spectrum shift at H/Hf ratio of 1.3. • Lifetime of the control rod quadruples because produced daughters of hafnium isotopes are absorbers. • Nuclear and thermal hydraulic characteristics of the reactor are as good as or better than B-10 enriched boron carbide. - Abstract: This study treats the feasibility of long-lived hafnium hydride control rod in a large sodium-cooled fast breeder reactor by nuclear and thermal analyses. According to the nuclear calculations, it is found that hydrogen absorption of hafnium triples the reactivity by the neutron spectrum shift at the H/Hf ratio of 1.3, and a hafnium transmutation mechanism that produced daughters are absorbers quadruples the lifetime due to a low incineration rate of absorbing nuclides under irradiation. That is to say, the control rod can function well for a long time because an irradiation of 2400 EFPD reduces the reactivity by only 4%. The calculation also reveals that the hafnium hydride control rod can apply to the reactor in that nuclear and thermal characteristics become as good as or better than 80% B-10 enriched boron carbide. For example, the maximum linear heat rate becomes 3% lower. Owing to the better power distribution, the required flow rate decreases approximately by 1%. Consequently, it is concluded on desk analyses that the long lived hafnium hydride control rod is feasible in the large sodium-cooled fast breeder reactor.

X-Ray Photoemission Study of the Oxidation of Hafnium

International Nuclear Information System (INIS)

Chourasia, R.; Hickman, J.L.; Miller, R.L.; Nixon, G.A.; Seabolt, M.A.

2011-01-01

About 20 angstrom of hafnium were deposited on silicon substrates using the electron beam evaporation technique. Two types of samples were investigated. In one type, the substrate was kept at the ambient temperature. After the deposition, the substrate temperature was increased to 100, 200, and 300 degree C. In the other type, the substrate temperature was held fixed at some value during the deposition. For this type, the substrate temperatures used were 100, 200, 300, 400, 500, 550, and 600 degree C. The samples were characterized in situ by the technique of X-ray photoelectron spectroscopy. No trace of elemental hafnium is observed in the deposited overlayer. Also, there is no evidence of any chemical reactivity between the overlayer and the silicon substrate over the temperature range used. The hafnium overlayer shows a mixture of the dioxide and the suboxide. The ratio of the suboxide to dioxide is observed to be more in the first type of samples. The spectral data indicate that hafnium has a strong affinity for oxygen. The overlayer gets completely oxidized to form HfO 2 at substrate temperature around 300 degree C for the first type of samples and at substrate temperature greater than 550 degree C for the second type

X-Ray Photoemission Study of the Oxidation of Hafnium

Directory of Open Access Journals (Sweden)

A. R. Chourasia

2009-01-01

Full Text Available About 20 Å of hafnium were deposited on silicon substrates using the electron beam evaporation technique. Two types of samples were investigated. In one type, the substrate was kept at the ambient temperature. After the deposition, the substrate temperature was increased to 100, 200, and 300∘C. In the other type, the substrate temperature was held fixed at some value during the deposition. For this type, the substrate temperatures used were 100, 200, 300, 400, 500, 550, and 600∘C. The samples were characterized in situ by the technique of X-ray photoelectron spectroscopy. No trace of elemental hafnium is observed in the deposited overlayer. Also, there is no evidence of any chemical reactivity between the overlayer and the silicon substrate over the temperature range used. The hafnium overlayer shows a mixture of the dioxide and the suboxide. The ratio of the suboxide to dioxide is observed to be more in the first type of samples. The spectral data indicate that hafnium has a strong affinity for oxygen. The overlayer gets completely oxidized to form HfO2 at substrate temperature around 300∘C for the first type of samples and at substrate temperature greater than 550∘C for the second type.

High temperature diffusion of hafnium in tungsten and a tungsten-hafnium carbide alloy

International Nuclear Information System (INIS)

Ozaki, Y.; Zee, R.H.

1994-01-01

Refractory metals and ceramics are used extensively in energy systems due to their high temperature properties. This is particularly important in direct conversion systems where thermal to electric conversion efficiency is a direct function of temperature. Tungsten, which has the highest melting temperature among elemental metals, does not possess sufficient creep resistance at temperature above 1,600 K. Different dispersion strengthened tungsten alloys have been developed to extend the usefulness of tungsten to higher temperatures. One of these alloys, tungsten with 0.4 mole percent of finely dispersed HfC particles (W-HfC), has the optimum properties for high temperature applications. Hafnium carbide is used as the strengthening agent due to its high chemical stability and its compatibility with tungsten. The presence of HfC particles retards the rate of grain growth as well as restricting dislocation motion. Both of which are beneficial for creep resistance. The long term behavior of this alloy depends largely on the evolution of its microstructure which is governed by the diffusion of its constituents. Data on the diffusion of carbon in tungsten and tungsten self-diffusion are available, but no direct measurements have been made on the diffusion of hafnium in tungsten. The only diffusion data available are estimated from a coarsening study and these data are highly unreliable. In this study, the diffusion behavior of hafnium in pure tungsten and in a W-HfC alloy was directly measured by means of Secondary Ion Mass Spectroscopy (SIMS). The selection of the W-HfC alloy is due to its importance in high temperature engineering applications, and its higher recrystallization temperature. The presence of HfC particles in tungsten restricts grain growth resulting in better high temperature creep resistance. The higher recrystallization temperature allows measurements to be made over a wider range of temperatures at a relatively constant grain size

Elaboration and characterisation of yttrium oxide and hafnium oxide powders by the sol-gel process

International Nuclear Information System (INIS)

Hours, T.

1988-01-01

The two classical sol-gel processes, colloidal and polymeric are studied for the preparation of yttrium oxide and hafnium oxide high performance powders. In the colloidal process, controlled and reproducible conditions for the preparation of yttrium oxide and hafnium oxide sols from salts or alkoxides are developed and the hydrothermal synthesis monodisperse hafnium oxide colloids is studied. The polymeric process is studied with hafnium ethyl-hexylate, hydrolysis kinetics for controlled preparation of sols and gels is investigated. Each step of preparation is detailed and powders obtained are characterized [fr

Modelling of Zirconium and Hafnium separation using continuous annular chromatography

International Nuclear Information System (INIS)

Moch-Setyadji; Endang Susiantini

2014-01-01

Nuclear degrees of zirconium in the form of a metal alloy is the main material for fuel cladding of NPP. Zirconium is also used as sheathing UO 2 kernel in the form of ZrC as a substitute of SiC in the fuel elements of High Temperature Reactor (HTR). Difficulty separating hafnium from zirconium because it has a lot of similarities in the chemical properties of Zr and Hf. Annular chromatography is a device that can be used for separating of zirconium and hafnium to obtain zirconium nuclear grade. Therefore, it is necessary to construct the mathematical modelling that can describe the separation of zirconium and hafnium in the annular chromatography containing anion resin dowex-1X8. The aim of research is to perform separation simulation by using the equilibrium model and mass transfer coefficient resulted from research. Zr and Hf feed used in this research were 26 and 1 g/l, respectively. Height of resin (L), angular velocity (ω) and the superficial flow rate (uz) was varied to determine the effect of each parameter on the separation of Zr and Hf. By using Kd and Dv values resulted previous research. Simulation results showed that zirconium and hafnium can be separated using a continuous annular chromatography with high resin (long bed) 50 cm, superficial flow rate of 0.001 cm/s, the rotation speed of 0.006 rad/min and 20 cm diameter annular. In these conditions the results obtained zirconium concentration of 10,303.226 g/m 3 and hafnium concentration of 12.324 g/m 3 (ppm). (author)

Joint titrimetric determination of zirconium and hafnium

International Nuclear Information System (INIS)

Vazquez, Cristina; Botbol, Moises; Bianco de Salas, G.N.; Cornell de Casas, M.I.

1980-01-01

A method for the joint titrimetric determination of zirconium and hafnium, which are elements of similar chemical behaviour, is described. The disodic salt of the ethylendiaminetetracetic acid (EDTA) is used for titration, while xilenol orange serves as final point indicator. Prior to titration it is important to evaporate with sulfuric acid, the solution resulting from the zirconium depolymerization process, to adjust the acidity and to eliminate any interferences. The method, that allows the quick and precise determination of zirconium and hafnium in quantities comprised between 0.01 and mg, was applied to the analysis of raw materials and of intermediate and final products in the fabrication of zirconium sponge and zircaloy. (M.E.L.) [es

Compositional characterization of hafnium alloy used as control rod material in nuclear reactor

International Nuclear Information System (INIS)

Sharma, P.K.; Bassan, M.K.T.; Avhad, D.K.; Singhal, R.K.

2014-01-01

Hafnium (Hf) is a heavy, steel-gray metal in the reactive metals group that is very closely related to zirconium (Zr) and forms a continuous solid-solution at all concentrations of zirconium and hafnium. Hafnium occurs naturally with zirconium at a ratio of approximately 1:50 and is produced exclusively as a co-product of nuclear-grade zirconium. It is used in a variety of applications where few substitutes are available. Thus with its relatively high thermal neutron absorption cross-section, hafnium's biggest application is as control rod material in nuclear reactors. During this work, major (Zirconium (Zr), Cobalt (Co) and Molybdenum (Mo)) and trace ((Iron (Fe), Nickel (Ni) and Titanium (Ti)) elements were measured in the bulk matrices of Hf. These materials are also associated with other impurities such as O, N, H etc.

Bond formation in hafnium atom implantation into SiC induced by high-energy electron irradiation

International Nuclear Information System (INIS)

Yasuda, H.; Mori, H.; Sakata, T.; Naka, M.; Fujita, H.

1992-01-01

Bilayer films of Hf (target atoms)/α-SiC (substrate) were irradiated with 2 MeV electrons in an ultra-high voltage electron microscope (UHVEM), with the electron beam incident on the hafnium layer. As a result of the irradiation, hafnium atoms were implanted into the SiC substrate. Changes in the microstructure and valence electronic states associated with the implantation were studied by a combination of UHVEM and Auger valence electron spectroscopy. The implantation process is summarized as follows. (1) Irradiation with 2 MeV electrons first induces a crystalline-to-amorphous transition in α-SiC. (2) Hafnium atoms which have been knocked-off from the hafnium layer by collision with the 2 MeV electrons are implanted into the resultant amorphous SiC. (3) The implanted hafnium atoms make preferential bonding to carbon atoms. (4) With continued irradiation, the hafnium atoms repeat the displacement along the beam direction and the subsequent bonding with the dangling hybrids of carbon and silicon. The repetition of the displacement and subsequent bonding lead to the deep implantation of hafnium atoms into the SiC substrate. It is concluded that implantation successfully occurs when the bond strength between a constituent atom of a substrate and an injected atom is stronger than that between constituent atoms of a substrate. (Author)

Hafnium Resonance Parameter Analysis Using Neutron Capture and Transmission Experiments

International Nuclear Information System (INIS)

MJ Trbovich; DP Barry; RE Slovacck; Y Danon; RC Block; JA Burke; NJ Drindak; G Leinweber; RV Ballad

2004-01-01

The focus of this work is to determine resonance parameters for stable hafnium isotopes in the 0.005-200 eV region, with special emphasis on the overlapping 176 Hf and 178 Hf resonances near 8 eV. The large neutron cross section of hafnium, combined with its corrosion resistance and excellent mechanical properties, make it a useful material for controlling nuclear reactions. Experiments measuring neutron capture and transmission were performed at the Rensselaer Polytechnic Institute (RPI) electron linear accelerator (LINAC) using the time of flight method. 6 Li glass scintillation detectors were used for transmission experiments at flight path lengths of 15 and 25 m. Capture experiments were done using a sixteen section NaI(Tl) multiplicity detector at a flight path length of 25 m. These experiments utilized various thicknesses of metallic and isotopically-enriched liquid samples. The liquid samples were designed to provide information on the 176 Hf and 178 Hf contributions to the 8 eV doublet without saturation. Data analysis was done using the R-matrix Bayesian code SAMMY version M6 beta. SAMMY is able to account for experimental resolution effects for each of the experimental setups at the RPI LINAC, and also can correct for multiple scattering effects in neutron capture yield data. The combined capture and transmission data analysis yielded resonance parameters for all hafnium isotopes from 0.005-200 eV. Resonance integrals were calculated along with errors for each hafnium isotope using the NJOY [1] and INTER [2] codes. The isotopic resonance integrals calculated were significantly different than previously published values; however the calculated elemental hafnium resonance integral changed very little

Zirconium and hafnium in the southeastern Atlantic States

Science.gov (United States)

Mertie, J.B.

1958-01-01

The principal source of zirconium and hafnium is zircon, though a minor source is baddeleyite, mined only in Brazil. Zircon is an accessory mineral in igneous, metamorphic, and sedimentary rocks, but rarely occurs in hardrock in minable quantities. The principal sources of zircon are therefore alluvial deposits, which are mined in many countries of five continents. The principal commercial deposits in the United States are in Florida, though others exist elsewhere in the southeastern Coastal Plain. The evidence indicates that conditions for the accumulation of workable deposits of heavy minerals were more favorable during the interglacial stages of the Pleistocene epoch than during Recent time. Therefore detrital ores of large volume and high tenor are more likely to be found in the terrace deposits than along the present beaches. Other concentrations of heavy minerals, however, are possible at favored sites close to the Fall Line where the Tuscaloosa formation rests upon the crystalline rocks of the Piedmont province. A score of heavy and semiheavy minerals occur in the detrital deposits of Florida, but the principal salable minerals are ilmenite, leucoxene, rutile, and zircon, though monazite and staurolite are saved at some mining plants. Commercial deposits of heavy minerals are generally required to have a tenor of 4 percent, though ores with a lower tenor can be mined at a profit if the content of monazite is notably high. The percentages of zircon in the concentrates ranges from 10 to 16 percent, and in eastern Florida from 13 to 15 percent. Thus the tenor in zircon of the ore-bearing sands ranges from 0.4 to 0.6 percent. The content of hafnium in zircon is immaterial for many uses, but for some purposes very high or very low tenors in hafnium are required. Alluvial zircon cannot be separated into such varieties, which, if needed, must be obtained from sources in bedrock. It thus becomes necessary to determine the Hf : Zr ratios in zircon from many kinds of

Niobium and hafnium grown on porous membranes

International Nuclear Information System (INIS)

Morant, C.; Marquez, F.; Campo, T.; Sanz, J.M.; Elizalde, E.

2010-01-01

In this work we report on a method for fabricating highly ordered nanostructures of niobium and hafnium metals by physical vapour deposition using two different templates: anodized aluminum oxide membranes (AAO) and zirconium onto AAO membranes (Zr/AAO). The growth mechanism of these metal nanostructures is clearly different depending on the material used as a template. A different morphology was obtained by using AAO or Zr/AAO templates: when the metal is deposited onto AAO membranes, nanospheres with ordered hexagonal regularity are obtained; however, when the metal is deposited onto a Zr/AAO template, highly ordered nanocones are formed. The experimental approach described in this work is simple and suitable for synthesizing nanospheres or nanoholes of niobium and hafnium metals in a highly ordered structure.

Analytical study of zirconium and hafnium α-hydroxy carboxylates

International Nuclear Information System (INIS)

Terra, V.R.

1991-01-01

The analytical study of zirconium and hafnium α-hydroxy carboxylates was described. For this purpose dl-mandelic, dl-p-bromo mandelic, dl-2-naphthyl glycolic, and benzilic acids were prepared. These were used in conjunction with glycolic, dl-lactic, dl-2-hydroxy isovaleric, dl-2-hydroxy hexanoic, and dl-2-hydroxy dodecanoic acids in order to synthesize the zirconium(IV) and hafnium(IV) tetrakis(α-hydroxy carboxylates). The compounds were characterized by melting point determination, infrared spectroscopy, thermogravimetric analysis, calcination to oxides and X-ray diffractometry by the powder method. (C.G.C)

High temperature evaporation of titanium, zirconium and hafnium carbides

International Nuclear Information System (INIS)

Gusev, A.I.; Rempel', A.A.

1991-01-01

Evaporation of cubic nonstoichiometric carbides of titanium, zirconium and hafnium in a comparatively low-temperature interval (1800-2700) with detailed crystallochemical sample certification is studied. Titanium carbide is characterized by the maximum evaporation rate: at T>2300 K it loses 3% of sample mass during an hour and at T>2400 K titanium carbide evaporation becomes extremely rapid. Zirconium and hafnium carbide evaporation rates are several times lower than titanium carbide evaporation rates at similar temperatures. Partial pressures of metals and carbon over the carbides studied are calculated on the base of evaporation rates

Determination of hafnium, molybdenum, and vanadium in niobium and niobium-based alloys by atomic absorption spectrometry

International Nuclear Information System (INIS)

Ide, Kunikazu; Kobayashi, Takeshi; Sudo, Emiko.

1985-01-01

The analytical procedure is as follows: Weigh 1 g of a sample and put it into a 100 cm 3 PTFE beaker. Add 5 ml of distilled water and 5 ml of hydrofluoric acid, and then heat the solution on a hot plate, adding 3 ml of nitric acid dropwise. Dilute the solution to 100 cm 3 with distilled water. When hafnium is determined, add 2 g of diammonium titanium hexafluoride ((NH 4 ) 2 TiF 6 )) before dilution. Working standard solutions are prepared by adding the stock standard solutions of hafnium, molybdenum, and vanadium into niobium solutions. When hafnium is determined, add 2 g of (NH 4 ) 2 TiF 6 and the alloying elements in amounts corresponding to those in sample solutions into the working standard solutions. The tolerable amounts of hydrofluoric acid were 2.9 M, 2.1 M, and 3.1 M and those of nitric acid were 1.0 M, 1.6 M, and 1.6 M for hafnium, molybdenum, and vanadium, respectively. It was found that (NH 4 ) 2 TiF 6 greatly increased the sensitivity for hafnium determination. Niobium showed minus effect for hafnium and plus effect for molybdenum and vanadium. The atomic absorption of molybdenum and vanadium were not influenced by the presence of 20 % of each alloying element, while the atomic absorption of hafnium was given plus effect by 20 % of zirconium, iron, cobalt, nickel, manganese, chromium or vanadium and minus effect by 20 % tungsten. The analytical values of hafnium, molybdenum, and vanadium in niobium-based alloys by this method showed a good agreement with those by X-ray fluorescence analysis. The lower limits of determination (S/N=2) were 0.05, 0.001, and 0.002 % and the relative standard deviation were 3, 1, and 1.5 % for hafnium, molybdenum, and vanadium, respectively. (author)

Separation of zirconium from hafnium by ion exchange

Energy Technology Data Exchange (ETDEWEB)

Felipe, Elaine C.B.; Palhares, Hugo G.; Ladeira, Ana Claudia Q., E-mail: elainecfelipe@yahoo.com.br, E-mail: hugopalhares@gmail.com, E-mail: ana.ladeira@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2013-07-01

Zirconium and hafnium are two of the most important metals for the nuclear industry. Hafnium occurs in all zirconium ores usually in the range 2 - 3%. However, for the most nuclear industry applications, it is necessary to use a zirconium of extremely pure level. The current work consists in the separation of zirconium and hafnium by the ion exchange method in order to obtain a zirconium concentrate of high purity. The zirconium and hafnium liquors were produced from the leaching of the Zr(OH){sub 4} and Hf(OH){sub 4} with nitric acid for 24 hours. From these two liquors it was prepared one solution containing 7.5 x 10{sup -2} mol L{sup -1} of Zr and 5.8 x 10{sup -3} mol L{sup -1} of Hf with acidity of 1 M. Ion exchange experiments were carried out in batch with the resins Dowex 50WX4, Dowex 50WX8 100, Dowex 50WX8 50, Amberlite IR-120 and Marathon C at constant temperature 28 deg C. Other variables such as, acidity and agitation were kept constant. The data were adjusted to Langmuir equation in order to calculate the maximum loading capacity (q{sub max}) of the resins, the distribution coefficient (K{sub d}) for Zr and Hf and the separation factor (α{sub Hf}{sup Zr} ). The results of maximum loading capacity (q{sub max}) for Zr and Hf, in mmol g{sup -}1, showed that the most suitable resins for columns experiments are: Dowex 50WX4 50 (q{sub max} Z{sub r} = 2.21, Hf = 0.18), Dowex 50WX8 50 (q{sub max} Zr = 1.89, Hf = 0.13) and Amberlite (q{sub max} Zr = 1.64, Hf = 0.12). However, separations factors, α{sub Hf}{sup Zr}, showed that the resins are not selective. (author)

On the stabilization of niobium(V) solutions by zirconium(IV) and hafnium(IV)

DEFF Research Database (Denmark)

Sørensen, E.; Bjerre, A.B.

1992-01-01

Niobium cannot be separated from zirconium or hafnium when these elements occur together in solution with common anions such as chloride and sulphate. This is ascribed to the co-polymerization of niobium(V) and the hydrolysed ionic species of zirconium(IV) and hafnium(IV) to form colloidal...

Analysis of hafnium in zirconium alloys

International Nuclear Information System (INIS)

Kondo, Isao; Sakai, Fumiaki; Ohuchi, Yoshifusa; Nakamura, Hisashi

1977-01-01

It is required to analyse alloying components and impurity elements in the acceptance analysis of zirconium alloys as the material for fuel cladding tubes and pressure tubes for advanced thermal reactors. Because of extreme similarity in chemical properties between zirconium and hafnium, about 100 ppm of hafnium is usually contained in zirconium alloys. Zircaloy-2 alloy and 2.5% Nb-zirconium with the addition of hafnium had been prepared as in-house standard samples for rapid analysis. Study was made on fluorescent X-ray analysis and emission spectral analysis to establish the analytical method. By using these in-house standard samples, acceptance analysis was successfully carried out for the fuel cladding tubes for advanced thermal reactors. Sulfuric acid solution was prepared from JAERI-Z 1, 2 and 3, the standard sample for zircaloy-2 prepared by the Analytical Committee on Nuclear Fuel and Reactor Materials, JAERI, and zirconium oxide (Hf 1 ppm/Zr). Standard Hf solution was added to the sulfuric acid solution step by step, to make up a series of the standard oxide samples by the precipitation process. By the use of these standard samples, the development of the analytical method and joint analysis were made by the three-member analytical technique research group including PNC. The analytical precision for the fluorescent X-ray analysis was improved by attaching a metallic yttrium filter to the window of an X-ray tube so as to suppress the effect due to zirconium matrix. The variation factor of the joint analysis was about 10% to show good agreement, and the indication value was determined. (Kobatake, H.)

Knight shift in scandium and its alloys with hafnium and titanium

International Nuclear Information System (INIS)

Chachkhiani, Z.B.; Chechernikov, V.I.; Martynova, L.F.; Nidel'ko, V.I.; Chachkhiani, L.G.; Georgadze, G.S.

1981-01-01

Results of the investigation of NMR on 45 Sc nuclei and magnetic susceptibility of scandium and its solid solutions with titanium and hafnium are presented. It is shown that the existing hybridization of S and d zones in pure scandium and its alloys with titanium and hafnium affects the Knight shift reducing the value of the contact contribution. The temperature behaviour of the Knight shift from the temperature dependence and spin susceptibility of collectivized d electrons [ru

Composition and microstructure of zirconium and hafnium germanates obtained by different chemical routes

International Nuclear Information System (INIS)

Utkin, A.V.; Prokip, V.E.; Baklanova, N.I.

2014-01-01

The phase composition and morphology of zirconium and hafnium germanates synthesized by ceramic and co-precipitation routes were studied. The products were characterized using high-temperature X-ray diffraction analysis (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and thermal (TG/DTA) analysis. To investigate the phase composition and stoichiometry of compounds the unit cell parameters were refined by full-profile Rietveld XRD analysis. The morphology of products and its evolution during high-temperature treatment was examined by SEM analysis. It was stated that there is the strong dependence of the phase composition and morphology of products on the preparation route. The ceramic route requires a multi-stage high-temperature treatment to obtain zirconium and hafnium germanates of 95% purity or more. Also, there are strong diffusion limitations to obtain hafnium germanate Hf 3 GeO 8 by ceramic route. On the contrary, the co-precipitation route leads to the formation of nanocrystalline single phase germanates of stoichiometric composition at a relatively low temperatures (less than 1000 °C). The results of quantitative XRD analysis showed the hafnium germanates are stoichiometric compounds in contrast to zirconium germanates that form a set of solid solutions. This distinction may be related to the difference in the ion radii of Zr and Hf. - Graphical abstract: The phase composition and morphology of zirconium and hafnium germanates synthesized by ceramic and co-precipitation routes were studied. It was stated that there is the strong dependence of the phase composition and morphology of products on the preparation route. Display Omitted - Highlights: • Zr and Hf germanates were synthesized by ceramic and co-precipitation routes. • The morphology of products depends on the synthesis parameters. • Zirconium germanates forms a set of solid solutions. • Hafnium germanates are stoichiometric compounds

Recovery of hafnium radioisotopes from a proton irradiated tantalum target

International Nuclear Information System (INIS)

Taylor, W.A.; Garcia, J.G.; Hamilton, V.T.; Heaton, R.C.; Jamriska, D.J.; Ott, M.A.; Philips, D.R.; Radzinski, S.D.

1998-01-01

The 178m2 Hf nucleus, with its long half-life (31 y) and high-spin isomeric state (16 + ) is desired for new and exotic nuclear physics studies. The Los Alamos Radioisotope Program irradiated a kilogram of natural tantalum at the Los Alamos Meson Physics Facility in early 1981. After fifteen years of decay, this target was ideal for the recovery of 178m2 Hf. There was more than a millicurie of 178m2 Hf produced during this irradiation and there has been a sufficient period of time for most of the other hafnium radioisotopes to decayed away. Traditionally, separation techniques for recovering hafnium isotopes from tantalum targets employ solvent extractions with reagents that are considered hazardous. These techniques are no longer condoned because they generate a mixed-waste (radioactive and hazardous components) that can not be treated for disposal. In this paper we describe a new and unique procedure for the recovery of hafnium radioisotopes from a highly radioactive, proton irradiated, tantalum target using reagents that do not contribute a hazardous waste component. (author)

Investigation of colourless complexes of thorium, hafnium and zirconium

International Nuclear Information System (INIS)

Kiciak, S.; Stefanowicz, T.; Gontarz, H.; Swit, Z.

1980-01-01

The investigations conducted in the Institute of General Chemistry of Poznan Technical University in partial cooperation with Kharkhof Technical University related with thorium, hafnium and zirconium complexes are reviewed. (author)

Separation process of zirconium and hafnium; Procede de separation du zirconium et du hafnium

Energy Technology Data Exchange (ETDEWEB)

Hure, J; Saint-James, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1955-07-01

About the separation different processes of zirconium-hafnium, the extraction by solvent in cross-current is the most easily the process usable on an industrial scale. It uses tributyl phosphate as solvent, diluted with white spirit to facilitate the decanting. Some exploratory tests showed that nitric environment seemed the most favorable for extraction; but a lot of other factors intervene in the separation process. We studied the influence of the acidity successively, the NO{sub 3}{sup -} ions concentration, the role of the cation coming with NO{sub 3}{sup -}, as well as the influence of the concentration of zirconium in the solution on the separation coefficient {beta} = {alpha}{sub Zr} / {alpha}{sub Hf}. (M.B.) [French] Des differents procedes de separation zirconium-hafnium, l'extraction par solvant en contre-courant est le procede le plus facilement utilisable a l'echelle industrielle. On utilise comme solvant le phosphate de tributyle, dilue avec du white spirit pour faciliter les decantations. Des essais preliminaires ont montre que le milieu nitrique semblait le plus favorable a l'extraction; mais beaucoup d'autres facteurs interviennent dans le processus de separation. Nous avons etudie successivement l'influence de l'acidite, celle de la concentration en ions NO{sub 3}{sup -}, le role du cation accompagnant NO{sub 3}{sup -}, ainsi que l'influence de la concentration en zirconium de la solution sur le coefficient de separation {beta} = {alpha}{sub Zr} / {alpha}{sub Hf}. (MB)

Heterogeneity of Human Neutrophil CD177 Expression Results from CD177P1 Pseudogene Conversion.

Directory of Open Access Journals (Sweden)

Zuopeng Wu

2016-05-01

Full Text Available Most humans harbor both CD177neg and CD177pos neutrophils but 1-10% of people are CD177null, placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia. By deep sequencing the CD177 locus, we catalogued CD177 single nucleotide variants and identified a novel stop codon in CD177null individuals arising from a single base substitution in exon 7. This is not a mutation in CD177 itself, rather the CD177null phenotype arises when exon 7 of CD177 is supplied entirely by the CD177 pseudogene (CD177P1, which appears to have resulted from allelic gene conversion. In CD177 expressing individuals the CD177 locus contains both CD177P1 and CD177 sequences. The proportion of CD177hi neutrophils in the blood is a heritable trait. Abundance of CD177hi neutrophils correlates with homozygosity for CD177 reference allele, while heterozygosity for ectopic CD177P1 gene conversion correlates with increased CD177neg neutrophils, in which both CD177P1 partially incorporated allele and paired intact CD177 allele are transcribed. Human neutrophil heterogeneity for CD177 expression arises by ectopic allelic conversion. Resolution of the genetic basis of CD177null phenotype identifies a method for screening for individuals at risk of CD177 isoimmunisation.

Strong influence of polymer architecture on the microstructural evolution of hafnium-alkoxide-modified silazanes upon ceramization.

Science.gov (United States)

Papendorf, Benjamin; Nonnenmacher, Katharina; Ionescu, Emanuel; Kleebe, Hans-Joachim; Riedel, Ralf

2011-04-04

The present study focuses on the synthesis and ceramization of novel hafnium-alkoxide-modified silazanes as well as on their microstructure evolution at high temperatures. The synthesis of hafnia-modified polymer-derived SiCN ceramic nanocomposites is performed via chemical modification of a polysilazane and of a cyclotrisilazane, followed by cross-linking and pyrolysis in argon atmosphere. Spectroscopic investigation (i.e., NMR, FTIR, and Raman) shows that the hafnium alkoxide reacts with the N-H groups of the cyclotrisilazane; in the case of polysilazane, reactions of N-H as well as Si-H groups with the alkoxide are observed. Consequently, scanning and transmission electron microscopy studies reveal that the ceramic nanocomposites obtained from cyclotrisilazane and polysilazane exhibited markedly different microstructures, which is a result of the different reaction pathways of the hafnium alkoxide with cyclotrisilazane and with polysilazane. Furthermore, the two prepared ceramic nanocomposites are unexpectedly found to exhibit extremely different high-temperature behavior with respect to decomposition and crystallization; this essential difference is found to be related to the different distribution of hafnium throughout the ceramic network in the two samples. Thus, the homogeneous distribution of hafnium observed in the polysilazane-derived ceramic leads to an enhanced thermal stability with respect to decomposition, whereas the local enrichment of hafnium within the matrix of the cyclotrisilazane-based sample induces a pronounced decomposition upon annealing at high temperatures. The results indicate that the chemistry and architecture of the precursor has a crucial effect on the microstructure of the resulting ceramic material and consequently on its high-temperature behavior. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Separation of hafnium from zirconium in sulfuric acid solutions using pressurized ion exchange

International Nuclear Information System (INIS)

Hurst, F.J.

1981-01-01

High-resolution pressurized ion exchange has been used successfully to study and separate hafnium and zirconium sulfate complexes by chromatographic elution from Dowex 50W-X8 (15 to 25 μm) resin with sulfuric acid solutions. Techniques were developed to continuously monitor the column effluents for zirconium and hafnium by reaction with fluorometric and colorimetric reagents. Since neither reagent was specific for either metal ion, peak patterns were initially identified by using the stable isotopes 90 Zr and 180 Hf as fingerprints of their elution position. Distribution ratios for both zirconium and hafnium decrease as the inverse fourth power of the sulfuric acid concentration below 2N and as the inverse second power at higher acid concentration. The hafnium-to-zirconium separation factor is approximately constant (approx. 8) over the 0.5 to 3N range. Under certain conditions, an unseparated fraction was observed that was not retained by the resin. The amount of this fraction which is thought to be a polymeric hydrolysis product appears to be a function of metal and sulfuric acid concentrations. Conditions are being sought to give the highest zirconium concentration and the lowest acid concentration that can be used as a feed material for commercial scale-up in the continuous annular chromatographic (CAC) unit without formation of the polymer

Separation of zirconium and hafnium from acompanying elements by paper chromatography in the systems of alcohol-acid

International Nuclear Information System (INIS)

Lebedeva, G.G.; Viktorova, M.E.

1980-01-01

Solvents have been chosen and investigated which provide expressed separation of zirconium and hafnium at the analysis of mineral raw materials by paper chromatography. The systems with HNO 3 and HCl containing methyl, ethyl, propyl and butyl alcohols have been studied as mobile phases for separation of zirconium and hafnium. It has been shown that alcohol contents and solvent acidity affect the Rsub(f) value of these elements. The C 2 H 5 OH-5MHCl and C 2 H 5 OH-5MHNO 3 systems are most optimal for pre-concentration of zirconium and hafnium

Study of the production of 177Lu through 176Yb (n, γ) 177Yb → 177Lu nuclear reaction

International Nuclear Information System (INIS)

Silva, Giovana Pasqualini da; Osso Junior, Joao Alberto

2007-01-01

The beta minus emitter 177 Lu is a promising therapeutic radioisotope for the curative treatment of cancer using labelled proteins. It has a half - life of T 1/2 = 6.71 day and maximum and average β - energies of 421 and 133 keV, resulting in a short range of radiation in tissue. The decay is accompanied by the emission of low energy γ-radiation with 208.3 keV (11%) and 113 keV (6.4%) suitable for simultaneous imaging, 177 Lu can be produced by two different routes, namely, by irradiation of natural Lu 2 O 3 target ( 176 Lu, 2.6%) or enriched (in 176 Lu) Lu 2 O 3 target, as also by irradiation of Yb target (Yb 2 O 3 ) followed by radiochemical separation of 177 Lu from Yb isotopes. The objective of this work is to study the production of 177 Lu through the indirect 176 Yb(n,γ) 177 Yb → 177 Lu nuclear reaction. The results of the production yield of 177 Lu will be shown and compared with the direct reaction. The method of choice for the chemical separation between Lu and Yb was the ion exchange, using an cation exchange resin in Cl - form and α-HIBA as eluent. Preliminary results showed a good separation of 177 Lu from Yb 2 O 3 indirect targets. (author)

Low-voltage bendable pentacene thin-film transistor with stainless steel substrate and polystyrene-coated hafnium silicate dielectric.

Science.gov (United States)

Yun, Dong-Jin; Lee, Seunghyup; Yong, Kijung; Rhee, Shi-Woo

2012-04-01

The hafnium silicate and aluminum oxide high-k dielectrics were deposited on stainless steel substrate using atomic layer deposition process and octadecyltrichlorosilane (OTS) and polystyrene (PS) were treated improve crystallinity of pentacene grown on them. Besides, the effects of the pentacene deposition condition on the morphologies, crystallinities and electrical properties of pentacene were characterized. Therefore, the surface treatment condition on dielectric and pentacene deposition conditions were optimized. The pentacene grown on polystyrene coated high-k dielectric at low deposition rate and temperature (0.2-0.3 Å/s and R.T.) showed the largest grain size (0.8-1.0 μm) and highest crystallinity among pentacenes deposited various deposition conditions, and the pentacene TFT with polystyrene coated high-k dielectric showed excellent device-performance. To decrease threshold voltage of pentacene TFT, the polystyrene-thickness on high-k dielectric was controlled using different concentration of polystyrene solution. As the polystyrene-thickness on hafnium silicate decreases, the dielectric constant of polystyrene/hafnium silicate increases, while the crystallinity of pentacene grown on polystyrene/hafnium silicate did not change. Using low-thickness polystyrene coated hafnium silicate dielectric, the high-performance and low voltage operating (pentacene thin film transistor (μ: ~2 cm(2)/(V s), on/off ratio, >1 × 10(4)) and complementary inverter (DC gains, ~20) could be fabricated.

Primary hafnium metal sponge and other forms, approved standard 1973

International Nuclear Information System (INIS)

Anon.

1975-01-01

A specification is presented covering virgin hafnium metal commonly designated as sponge because of its porous, sponge-like texture; it may also be in other forms such as chunklets. The specification does not cover crystal bar

Evolution of the hafnium isotopic composition in the RBMK reactor

International Nuclear Information System (INIS)

Jurkevicius, A.; Remeikis, V.

2002-01-01

The isotopic composition of hafnium in the radial neutron flux sensor of the RBMK-1500 reactor, the rates of the neutron absorption on Hf isotopes and the neutron spectrum in the sensor were numerically modeled. The sequence SAS2 (Shielding Analysis Sequence) program from the package SCALE 4.4A and the HELIOS code system were used for calculations. It has been obtained that the overall neutron absorption rates in hafnium for the sensors located in the 2.4 % and 2.6 % enrichment uranium-erbium nuclear fuel assemblies are by 16 % and 19 % lower than in the 2.0 % enrichment uranium nuclear fuel assemblies. The overall neutron absorption rate in hafnium decreases 2.70-2.75 times due to the sensor burnup to 5800 MW d. The sensitivity of the Hf sensors to the thermal neutron flux increases twice due to the nuclear fuel assembly burnup to 3000 MW d. The corrective factors ξ d (I) at the different integral current I of the sensors and ξ td (E) at the different burnup E of the nuclear fuel assemblies were calculated. The obtained dependence ξ d (I) calculated numerically was compared to the experimental one determined by comparing signals of the fresh sensor and the sensor with the integral current I and by processing repeated calibration results of Hf sensors in RBMK-1500 reactors. The relative relationship coefficients K T (T FA ) were found for all RBMK-1500 nuclear fuel types. (author)

Preparation of hafnium metal by calciothermic reduction of HfO2

International Nuclear Information System (INIS)

Sharma, I.G.; Vijay, P.L.; Sehra, J.C.; Sundaram, C.V.

1975-01-01

Hafnium metal powder has been produced by the calciothermic reduction of hafnium oxide. The influence of various experimental parameters - such as amount of calcium in excess of stoichiometric requirement, temperature, and time of reduction - on the yield and purity of the metal has been studied. The metal powder obtained by reduction at 960 0 C (two hours) with a calcium excess of 70% analysed 600 ppm of oxygen and 147 ppm of nitrogen. A reduction efficiency of 96% has been achieved under these conditions. The refining of the powder by electron beam melting, fused salt electrolysis, and iodide process has been studied. The oxygen content in the metal could be brought down from 6900 to 148 ppm by electron beam melt-refining. (author)

ENTIRELY AQUEOUS SOLUTION-GEL ROUTE FOR THE PREPARATION OF ZIRCONIUM CARBIDE, HAFNIUM CARBIDE AND THEIR TERNARY CARBIDE POWDERS

Directory of Open Access Journals (Sweden)

Zhang Changrui

2016-07-01

Full Text Available An entirely aqueous solution-gel route has been developed for the synthesis of zirconium carbide, hafnium carbide and their ternary carbide powders. Zirconium oxychloride (ZrOCl₂.8H₂O, malic acid (MA and ethylene glycol (EG were dissolved in water to form the aqueous zirconium carbide precursor. Afterwards, this aqueous precursor was gelled and transformed into zirconium carbide at a relatively low temperature (1200 °C for achieving an intimate mixing of the intermediate products. Hafnium and the ternary carbide powders were also synthesized via the same aqueous route. All the zirconium, hafnium and ternary carbide powders exhibited a particle size of ∼100 nm.

On the phase formation of sputtered hafnium oxide and oxynitride films

International Nuclear Information System (INIS)

Sarakinos, K.; Music, D.; Mraz, S.; Baben, M. to; Jiang, K.; Nahif, F.; Braun, A.; Zilkens, C.; Schneider, J. M.; Konstantinidis, S.; Renaux, F.; Cossement, D.; Munnik, F.

2010-01-01

Hafnium oxynitride films are deposited from a Hf target employing direct current magnetron sputtering in an Ar-O 2 -N 2 atmosphere. It is shown that the presence of N 2 allows for the stabilization of the transition zone between the metallic and the compound sputtering mode enabling deposition of films at well defined conditions of target coverage by varying the O 2 partial pressure. Plasma analysis reveals that this experimental strategy facilitates control over the flux of the O - ions which are generated on the oxidized target surface and accelerated by the negative target potential toward the growing film. An arrangement that enables film growth without O - ion bombardment is also implemented. Moreover, stabilization of the transition sputtering zone and control of the O - ion flux without N 2 addition is achieved employing high power pulsed magnetron sputtering. Structural characterization of the deposited films unambiguously proves that the phase formation of hafnium oxide and hafnium oxynitride films with the crystal structure of HfO 2 is independent from the O - bombardment conditions. Experimental and theoretical data indicate that the presence of vacancies and/or the substitution of O by N atoms in the nonmetal sublattice favor the formation of the cubic and/or the tetragonal HfO 2 crystal structure at the expense of the monoclinic HfO 2 one.

Solvent extraction of titanium(IV), zirconium(IV) and hafnium(IV) salicylates using liquid ion exchangers

Energy Technology Data Exchange (ETDEWEB)

Sundaramurthi, N M; Shinde, V M

1989-02-01

A solvent extraction method is proposed for the extraction of quadrivalent titanium, zirconium an hafnium from salicylate media using liquid ion exchangers such as Aliquat 336 and trioctylamine dissolved in xylene. The optimum conditions were evaluated from a critical study of the following: pH, salicylate concentration, amine concentration, diluent and period of equilibration. The method allows the separation of titanium, zirconium and hafnium from binary mixtures containing commonly associated metal ions and is applicable to the analysis of real samples such as BCS-CRM 387 nimonic 901, BCS-CRM 243/4 ferro-titanium, BCS-CRM 307 magnesium alloy and BCS-CRM 388 zircon. Titanium is determined either with hydrogen peroxide or by atomic absorption spectrometry whereas zirconium and hafnium are determined spectrophotometrically with Alizarin Red S and Zylenol Orange, respectively. The results of both separation and analysis are reported. The method is precise, accurate and fast.

Solvent extraction of zirconium and hafnium using MIBK-HSCN-HCL process

International Nuclear Information System (INIS)

Borges, J.A.L.; Cunha, O.G.C. da

1985-01-01

The separation process of zirconium and hafnium, using MIBK as extractant in a set of mixer-settler is described. The chemical analysis was done by X-ray fluorescence and emission spectrography. (Author) [pt

Radiation effects on the electrical properties of hafnium oxide based MOS capacitors.

Energy Technology Data Exchange (ETDEWEB)

Petrosky, J. C. (Air Force Institute of Technology, Wright-Patterson Air Force Base, OH); McClory, J. W. (Air Force Institute of Technology, Wright-Patterson Air Force Base, OH); Bielejec, Edward Salvador; Foster, J. C. (Air Force Institute of Technology, Wright-Patterson Air Force Base, OH)

2010-10-01

Hafnium oxide-based MOS capacitors were investigated to determine electrical property response to radiation environments. In situ capacitance versus voltage measurements were analyzed to identify voltage shifting as a result of changes to trapped charge with increasing dose of gamma, neutron, and ion radiation. In situ measurements required investigation and optimization of capacitor fabrication to include dicing, cleaning, metalization, packaging, and wire bonding. A top metal contact of 200 angstroms of titanium followed by 2800 angstroms of gold allowed for repeatable wire bonding and proper electrical response. Gamma and ion irradiations of atomic layer deposited hafnium oxide on silicon devices both resulted in a midgap voltage shift of no more than 0.2 V toward less positive voltages. This shift indicates recombination of radiation induced positive charge with negative trapped charge in the bulk oxide. Silicon ion irradiation caused interface effects in addition to oxide trap effects that resulted in a flatband voltage shift of approximately 0.6 V also toward less positive voltages. Additionally, no bias dependent voltage shifts with gamma irradiation and strong oxide capacitance room temperature annealing after ion irradiation was observed. These characteristics, in addition to the small voltage shifts observed, demonstrate the radiation hardness of hafnium oxide and its applicability for use in space systems.

Investigation of chlorination of zirconium and hafnium and their compounds in discharge from hollow cathode

International Nuclear Information System (INIS)

Ioffe, R.B.; Korovin, Yu.I.

1978-01-01

The possibility is investigated of chlorinating various zirconium and hafnium compounds (metal, oxide, carbide) in a hot discharge from a hollow cathode with various chlorinating reagents: copper monochloride, nickel chloride, magnesium chloride, for the purpose of accelerating their entrance into the excitation zone. It has been shown thermodynamically and experimentally that chlorination of metal zirconium and hafnium and their carbides with copper monochloride in hot hollow cathode conditions provides a sharp increase in the intensity of the lines of these elements

Development and characterization of ultrathin hafnium titanates as high permittivity gate insulators

Science.gov (United States)

Li, Min

High permittivity or high-kappa materials are being developed for use as gate insulators for future ultrascaled metal oxide semiconductor field effect transistors (MOSFETs). Hafnium containing compounds are the leading candidates. Due to its moderate permittivity, however, it is difficult to achieve HfO2 gate structures with an EOT well below 1.0 nm. One approach to increase HfO2 permittivity is combining it with a very high-kappa material, such as TiO2. In this thesis, we systematically studied the electrical and physical characteristics of high-kappa hafnium titanates films as gate insulators. A series of HfxTi1-xO2 films with well-controlled composition were deposited using an MOCVD system. The physical properties of the films were analyzed using a variety of characterization techniques. X-ray micro diffraction indicates that the Ti-rich thin film is more immune to crystallization. TEM analysis showed that the thick stoichiometric HfTiO 4 film has an orthorhombic structure and large anisotropic grains. The C-V curves from the devices with the hafnium titanates films displayed relatively low hysteresis. In a certain composition range, the interfacial layer (IL) EOT and permittivity of HfxTi1-x O2 increases linearly with increasing Ti. The charge is negative for HfxTi1-xO2/IL and positive for Si/IL interface, and the magnitude increases as Hf increases. For ultra-thin films (less than 2 nm EOT), the leakage current increases with increasing HE Moreover, the Hf-rich sample has weaker temperature dependence of the current. In the MOSFET devices with the hafnium titanates films, normal transistor characteristics were observed, also electron mobility degradation. Next, we investigated the effects that different pre-deposition surface treatments, including HF dipping, NH3 surface nitridation, and HfO2 deposition, have on the electrical properties of hafnium titanates. Surface nitridation shows stronger effect than the thin HfO2 layer. The nitrided samples displayed a

Separation of zirconium and hafnium using paper distribution chromatography

International Nuclear Information System (INIS)

Lebedeva, G.G.; Viktorova, M.E.

1981-01-01

A method is suggested of chromatographic separation of zirconium and hafnium in a CCl 4 -tributyl phosphate system (1:9) containing KCl as a salting-out agent in 5 M HNO 3 at 28-30 deg C. Zr and Hf are deterfmined in articiial mixtures under optimal chromatography conditions using visual colorimetry [ru

Hafnium as a prospective absorber for VVER-1000 reactors of Ukraine

International Nuclear Information System (INIS)

Afanas'ev, A.A.; Konotop, Yu.F.; Odejchuk, N.L.

2000-01-01

Nuclear-physical parameters of hafnium having in mind its use as an absorber, are considered. Technical aspects of Hf production are exposed. Use of B 4 C/Hf absorber is twice cheaper than a standard one

Evaluation of thermodynamic data on zirconium and hafnium halides and oxyhalides by means of transport experiments

International Nuclear Information System (INIS)

Dittmer, G.; Niemann, U.

1987-01-01

A consistent set of thermodynamic data for zirconium and hafnium halides, oxides and oxyhalides was achieved. It was found that formation enthalpies of gaseous compounds could be derived from solubility measurements together with theoretical estimations and a revision of literature data. Free energy functions were calculated employing statistical mechanics. Data for liquid and solid compounds were obtained via sublimation and vaporization data. Chemical equilibria of zirconium and hafnium with halogens are discussed. 51 refs.; 16 figs.; 14 tabs

Electrodeposition in molten salts of metals used in nuclear industry: hafnium and uranium

International Nuclear Information System (INIS)

Serrano, K.

1998-01-01

The aim of this work is to study the electrodeposition in molten salts of metals used in nuclear industry: hafnium and uranium. The experiment is carried out in a molten alkaline halogenide medium in a temperature range between 670 and 750 degrees Celsius. The first part of this work concerns more particularly the electrochemical behaviour of the hafnium and uranium ions in the electrolytic solution. The reduction mechanisms of these ions have been studied by the use of three methods: cyclic voltametry, chrono-potentiometry and square wave voltametry. Results have shown that the process of metal deposition is difficult to explain because secondary reactions (as for instance: adsorption phenomena or cathodic deposit dissolution) occur. The uranium germination has then been studied by modelling of chrono-amperograms. The experiments have shown that the deposition is the result of the initial uranium crystal growth and depends on the electrolyte diffusion. The second part of this work deals with the implementation of hafnium and uranium deposition taking into account the preceding mechanistic studies. Depositions have all been observed by physical methods as for instance scanning electron microscopy. Particular experimental solutions (soluble anode, addition of fluoride ions to the electrolyte) have been used. The obtained deposition of hafnium is smooth and adheres very well to the substrate. The uranium depositions have been implemented with the use of a soluble anode. Uranium is deposited in a dendritic shape to the cathode. It has also been shown that the electro-kinetic parameters (temperature, uranium ions concentration, current density) have not an important influence on the dendritic morphology of the deposition. This morphology could be the consequence of particular convection movements to the surface of the cathode. (O.M.)

Synthesis and characterization of Ho3+ doped hafnium oxide TLD for radiation dosimeter

International Nuclear Information System (INIS)

Sekar, Nandakumar; Ganesan, Bharanidharan; Sahib, Hajee Reyaz Ali; Aruna, Prakasarao; Ganesan, Singaravelu; Thamilkumar, P.; Rai, R.R.

2017-01-01

Cancer is a dreaded disease which is treated by Radiotherapy, Chemotherapy and Surgery. Radiotherapy plays a vital role in treatment of cancer and recently measurements of invivo radiation dosimetric in patient is of great interest due to high dose gradients in advanced technology like IMRT, IGRT etc. Hence, for the last few decades, a great degree of interest has been shown for the hafnium oxide for radiation dosimetric applications, due to its high dielectric constant, wide band gap and better interface properties such as chemical stability, conduction band offset and thermodynamic stability. In the present study, Synthesis and characterization of Ho 3+ doped Hafnium oxide were carried out and its applications towards radiation dosimeter were investigated

Use of hafnium in control bars of nuclear reactors; Uso de hafnio en barras de control de reactores nucleares

Energy Technology Data Exchange (ETDEWEB)

Ramirez S, J.R.; Alonso V, G. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: jrrs@nuclear.inin-mx

2003-07-01

Recently the use of hafnium as neutron absorber material in nuclear reactors has been reason of investigation by virtue of that this material has nuclear properties as to the neutrons absorption and structural that can prolong the useful life of the control mechanisms of the nuclear reactors. In this work some of those more significant hafnium properties are presented like nuclear material. Also there are presented calculations carried out with the HELIOS code for fuel cells of uranium oxide and of uranium and plutonium mixed oxides under controlled conditions with conventional bars of boron carbide and also with similar bars to which are substituted the absorbent material by metallic hafnium, the results are presented in this work. (Author)

Plasma spraying of zirconium carbide – hafnium carbide – tungsten cermets

Czech Academy of Sciences Publication Activity Database

Brožek, Vlastimil; Ctibor, Pavel; Cheong, D.-I.; Yang, S.-H.

2009-01-01

Roč. 9, č. 1 (2009), s. 49-64 ISSN 1335-8987 Institutional research plan: CEZ:AV0Z20430508 Keywords : Plasma spraying * cermet coatings * microhardness * zirconium carbide * hafnium carbide * tungsten * water stabilized plasma Subject RIV: JH - Ceramics, Fire-Resistant Materials and Glass

Extraction of zirconium and hafnium thiocyanates by CH3COCH2CH.(CH3)2-HSCN solvent from chloride medium

International Nuclear Information System (INIS)

Okada, A.T.

1982-01-01

A zirconium-hafnium separation process for application in nuclear industry is presented. The extraction of zirconium and hafnium thiocyanates in chloride medium by hexone-HSCN solvent was studied. The extraction process was developed, varying the parameters, such as, concentrations of the metals, the thiocyanate ion, the sulphate ion and free acidity in aqueous phase. (Author) [pt

Separation process of zirconium and hafnium

International Nuclear Information System (INIS)

Hure, J.; Saint-James, R.

1955-01-01

About the separation different processes of zirconium-hafnium, the extraction by solvent in cross-current is the most easily the process usable on an industrial scale. It uses tributyl phosphate as solvent, diluted with white spirit to facilitate the decanting. Some exploratory tests showed that nitric environment seemed the most favorable for extraction; but a lot of other factors intervene in the separation process. We studied the influence of the acidity successively, the NO 3 - ions concentration, the role of the cation coming with NO 3 - , as well as the influence of the concentration of zirconium in the solution on the separation coefficient β = α Zr / α Hf . (M.B.) [fr

Study of the production of {sup 177}Lu through {sup 176}Yb (n, {gamma}) {sup 177}Yb {yields} {sup 177}Lu nuclear reaction

Energy Technology Data Exchange (ETDEWEB)

Silva, Giovana Pasqualini da; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: gpsilva@ipen.br; jaosso@ipen.br

2007-07-01

The beta minus emitter {sup 177}Lu is a promising therapeutic radioisotope for the curative treatment of cancer using labelled proteins. It has a half - life of T{sub 1/2} = 6.71 day and maximum and average {beta}{sup -} energies of 421 and 133 keV, resulting in a short range of radiation in tissue. The decay is accompanied by the emission of low energy {gamma}-radiation with 208.3 keV (11%) and 113 keV (6.4%) suitable for simultaneous imaging, {sup 177}Lu can be produced by two different routes, namely, by irradiation of natural Lu{sub 2}O{sub 3} target ({sup 176}Lu, 2.6%) or enriched (in {sup 176}Lu) Lu{sub 2}O{sub 3} target, as also by irradiation of Yb target (Yb{sub 2}O{sub 3}) followed by radiochemical separation of {sup 177}Lu from Yb isotopes. The objective of this work is to study the production of {sup 177}Lu through the indirect {sup 176}Yb(n,{gamma}){sup 177}Yb {yields} {sup 177}Lu nuclear reaction. The results of the production yield of {sup 177}Lu will be shown and compared with the direct reaction. The method of choice for the chemical separation between Lu and Yb was the ion exchange, using an cation exchange resin in Cl{sup -} form and {alpha}-HIBA as eluent. Preliminary results showed a good separation of {sup 177}Lu from Yb{sub 2}O{sub 3} indirect targets. (author)

Synthesis and characterization of hafnium oxide films for thermo and photoluminescence applications

International Nuclear Information System (INIS)

Guzman Mendoza, J.; Aguilar Frutis, M.A.; Flores, G. Alarcon; Garcia Hipolito, M.; Maciel Cerda, A.; Azorin Nieto, J.; Rivera Montalvo, T.; Falcony, C.

2010-01-01

Hafnium oxide (HfO 2 ) films were deposited by the ultrasonic spray pyrolysis process. The films were synthesized from hafnium chloride as raw material in deionized water as solvent and were deposited on corning glass substrates at temperatures from 300 to 600 deg. C. For substrate temperatures lower than 400 deg. C the deposited films were amorphous, while for substrate temperatures higher than 450 deg. C, the monoclinic phase of HfO 2 appeared. Scanning electron microscopy showed that the film's surface resulted rough with semi-spherical promontories. The films showed a chemical composition close to HfO 2 , with an Hf/O ratio of about 0.5. UV radiation was used in order to achieve the thermoluminescent characterization of the films; the 240 nm wavelength induced the best response. In addition, preliminary photoluminescence spectra, as a function of the deposition temperatures, are shown.

A study of a production process for hafnium-free zirconium from zircon

International Nuclear Information System (INIS)

Ratanalert, N.

1985-01-01

The purpose of this experiment was to extract and purify the zirconium from zircon. The effects of time of extraction and stripping of zirconium, concentration of feed solution, concentration of hydrochloric acid in stripping process, equilibrium curve of extraction of zirconium and hafnium and equilibrium curve of stripping zirconium or scrubbing hafnium were studied from standard zirconium and hafnium. The results, subsequently were applied to the extraction procedures for zirconium from zircon. Minus 100 mesh zircon was fused with sodium hydroxide in the ratio of 1 : 6 at 700 degree C for l hour. After fusion the zirconate was leached with water and dissolved in hot concentrated hydrochloric acid. Zirconyl chloride octahydrate crystallized out when the solution was cooled. An agueons solution of zirconyl chloride was used as the feed to the hexone - thiocyanate solvent extraction process. This was prepared by dissolving zirconyl chloride octahydrate crystal in waster. This zirconium feed solution in 1 M HCl and 1 M N H 4 CNS was extracted with 2.7 m N H 4 CNS in hexone and then stripped with 3.6 M HCl the aqueous phase was got rid of thiocyanate ion by extracting with pure hexone, then the zirconium in aqueous phase was precipitated with sulfuric acid and ammonium hydroxide at pH 1.8 - 2.0 and zirconium oxide was obtained by ignition at 700 degree C. The process could be modified to improve the purity of zirconium by using cation exchange resin to get rid of thiocyanate ion after solvent extraction process

Vapor pressure, heat capacities, and phase transitions of tetrakis(tert-butoxy)hafnium

Czech Academy of Sciences Publication Activity Database

Fulem, Michal; Růžička, K.

2011-01-01

Roč. 311, Dec. (2011), s. 25-29 ISSN 0378-3812 Institutional research plan: CEZ:AV0Z10100521 Keywords : tetrakis(tert-butoxy)hafnium * MO precursor * vapor pressure * heat capacity * vaporization enthalpy * enthalpy of fusion Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.139, year: 2011

Pentamethylcyclopentadienyl Zirconium and Hafnium Polyhydride Complexes : Synthesis, Structure, and Reactivity

NARCIS (Netherlands)

Visser, Cindy; Hende, Johannes R. van den; Meetsma, Auke; Hessen, Bart; Teuben, Jan H.

2001-01-01

The half-sandwich zirconium and hafnium N,N-dimethylaminopropyl complexes Cp*M[(CH2)3NMe2]Cl2 (Cp* = η5-C5Me5, M = Zr, 1; Hf, 2) and Cp*M[(CH2)3NMe2]2Cl (M = Zr, 3; Hf, 4) were synthesized by mono- or dialkylation of Cp*MCl3 with the corresponding alkyllithium and Grignard reagents. Hydrogenolysis

Properties of neutron-rich hafnium high-spin isomers

CERN Multimedia

Tungate, G; Walker, P M; Neyens, G; Billowes, J; Flanagan, K; Koester, U H; Litvinov, Y

It is proposed to study highly-excited multi-quasiparticle isomers in neutron-rich hafnium (Z=72) isotopes. Long half-lives have already been measured for such isomers in the storage ring at GSI, ensuring their accessibility with ISOL production. The present proposal focuses on:\\\\ (i) an on-line experiment to measure isomer properties in $^{183}$Hf and $^{184}$Hf, and\\\\ (ii) an off-line molecular breakup test using REXTRAP, to provide Hf$^{+}$ beams for future laser spectroscopy and greater sensitivity for the future study of more neutron-rich isotopes.

49 CFR 177.810 - Vehicular tunnels.

Science.gov (United States)

2010-10-01

... through any urban vehicular tunnel used for mass transportation. [Amdt. 177-52, 46 FR 5316, Jan. 19, 1981... 49 Transportation 2 2010-10-01 2010-10-01 false Vehicular tunnels. 177.810 Section 177.810 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY...

21 CFR 177.1420 - Isobutylene polymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Isobutylene polymers. 177.1420 Section 177.1420... FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1420 Isobutylene polymers. Isobutylene...

Ion-bombardment-induced reduction in vacancies and its enhanced effect on conductivity and reflectivity in hafnium nitride films

Energy Technology Data Exchange (ETDEWEB)

Gu, Zhiqing; Wang, Jiafu; Hu, Chaoquan; Zhang, Xiaobo; Dang, Jianchen; Gao, Jing; Zheng, Weitao [Jilin University, School of Materials Science and Engineering, Key Laboratory of Mobile Materials, MOE, and State Key Laboratory of Superhard Materials, Changchun (China); Zhang, Sam [Nanyang Technological University, School of Mechanical and Aerospace Engineering, Singapore (Singapore); Wang, Xiaoyi [Chinese Academy of Sciences, Key Laboratory of Optical System Advanced Manufacturing Technology, Changchun Institute of Optics, Fine Mechanics and Physics, Changchun (China); Chen, Hong [Jilin University, Department of Control Science and Engineering, Changchun (China)

2016-08-15

Although the role of ion bombardment on electrical conductivity and optical reflectivity of transition metal nitrides films was reported previously, the results were controversial and the mechanism was not yet well explored. Here, we show that proper ion bombardment, induced by applying the negative bias voltage (V{sub b}), significantly improves the electrical conductivity and optical reflectivity in rocksalt hafnium nitride films regardless of level of stoichiometry (i.e., in both near-stoichiometric HfN{sub 1.04} and over-stoichiometric HfN{sub 1.17} films). The observed improvement arises from the increase in the concentration of free electrons and the relaxation time as a result of reduction in nitrogen and hafnium vacancies in the films. Furthermore, HfN{sub 1.17} films have always much lower electrical conductivity and infrared reflectance than HfN{sub 1.04} films for a given V{sub b}, owing to more hafnium vacancies because of larger composition deviation from HfN exact stoichiometry (N:Hf = 1:1). These new insights are supported by good agreement between experimental results and theoretical calculations. (orig.)

33 CFR 117.177 - Mud Slough.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Mud Slough. 117.177 Section 117.177 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements California § 117.177 Mud Slough. The draw of the Union Pacific...

49 CFR 177.817 - Shipping papers.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Shipping papers. 177.817 Section 177.817... Information and Regulations § 177.817 Shipping papers. (a) General requirements. A person may not accept a... received a shipping paper prepared in accordance with part 172 of this subchapter or the material is...

46 CFR 177.300 - Structural design.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Structural design. 177.300 Section 177.300 Shipping...) CONSTRUCTION AND ARRANGEMENT Hull Structure § 177.300 Structural design. Except as otherwise allowed by this subpart, a vessel must comply with the structural design requirements of one of the standards listed below...

46 CFR 177.920 - Storm rails.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Storm rails. 177.920 Section 177.920 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) CONSTRUCTION AND ARRANGEMENT Rails and Guards § 177.920 Storm rails. Suitable storm rails or hand grabs must be...

Results for heterogeneous poisoning of the critical HTR-test facility KAHTER using absorber elements containing hafnium and boron

International Nuclear Information System (INIS)

Drueke, V.; Filges, D.; Nabi, R.; Neef, R.D.; Paul, N.; Schaal, H.

1979-10-01

Experiments and checking computations for investigating the initial-core poisoning of the pebble bed high temperature reactor are described. Following the example of the THTR-300, THTR absorber elements poisoned with hafnium/boron were added to the THTR fuel- and graphite elements of the KAHTER core. Three different hafnium-boron poisoned core loadings, corresponding to 2.7, 5.3 and 8% reactivity compensation, were used in the experiments. For purposes of comparison, two cores exclusively boron poisoned were also studied. The poisoning of these cores correspond to 2.7 and 8% reactivity compensation. The experiments and checking computations should serve to test the accuracy of the theoretical models and data sets in modeling the reactivity effects of absorber poisoned elements in the THTR. In particular, the applicability of the nuclear data of hafnium and the treatment of resonance calculations should be verified. In addition, to determining critical masses and ksub(eff), special emphasis was placed in the experiments on the exact determination of all reactivity effects. In some cases, repeated loading of a configuration also provided a measure of the reproducibility of ksub(eff). The experiments were checked computationally using the GAMTEREX code package and the program system RSYST. These two computation packages contain different data bases, - although the hafnium data are identical -, and the computing models differ in certain phases of the calculations. Both code systems compute ksub(eff) values to within the present accuracy requirements, whereas the program system RSYST gives better agreement with experimental measurements. (orig.) 891 RW/orig. 892 RDG [de

21 CFR 177.1680 - Polyurethane resins.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyurethane resins. 177.1680 Section 177.1680 Food... of Single and Repeated Use Food Contact Surfaces § 177.1680 Polyurethane resins. The polyurethane...) For the purpose of this section, polyurethane resins are those produced when one or more of the...

radiolabeling of DOTA-substance P with 177Lu and biodistribution of 177Lu-DOTA-substance P

International Nuclear Information System (INIS)

Liang Jixin; Li Hongyu; Xiang Xueqin; Luo Zhifu; Luo Hongyi; Hu Liansheng; Chen Yang; Zhuang Ling; Deng Xinrong

2012-01-01

The aim of this project is to evaluate the biodistribution of 177 Lu-DOTA-SP in normal mice and in PANC-1 tumor bearing nude mice and to pave the way for its potentially medical application. In this study, 177 Lu-DOTA-SP was successfully prepared with labeling yield of greater than 90% at optimized conditions and more than 98% of radiochemical purity after C18 Sep-Pak purification. 177 Lu-DOTA-SP showed good stability in saline and in 5% serum while it decomposed slowly in 10% serum. Biodistribution studies in normal mice showed high uptake of 177 Lu-DOTA-SP in the kidneys, indicating the excretion mainly by renal pathway. In addition, 177 Lu-DOTA-SP was washed out from the blood quickly. Bio- distribution of 177 Lu-DOTA-SP in PANC-1 tumor bearing mice showed higher uptake in pancreatic tumor than that in normal pancreas, indicating the presence of NK-1 receptors in PANC-1 pancreatic tumor. However, from SPECT image, no radioactivity accumulation was observed in PANC-1 tumor. Further evaluation is needed to confirm its potential application for radiotherapy of pancreatic cancers. (authors)

Thermal behaviour of hafnium diethylenetriaminepentaacetate studied using the perturbed angular correlation technique

Energy Technology Data Exchange (ETDEWEB)

Chain, Cecilia Y. [Universidad Nacional de La Plata (Argentina). Dept. de Fisica; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), La Plata (Argentina). IFLP-CCT; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina); Rivas, Patricia [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), La Plata (Argentina). IFLP-CCT; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina); Universidad Nacional de La Plata (Argentina). Facultad de Ciencias Agrarias y Forestales; Pasquevich, Alberto F. [Universidad Nacional de La Plata (Argentina). Dept. de Fisica; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), La Plata (Argentina). IFLP-CCT; Comision de Investigaciones Cientificas de la Provincia de Buenos Aires (CIC-PBA) (Argentina)

2014-07-01

Polyaminecarboxilic ligands like diethylenetriaminepentaacetic acid form stable complexes with many heavy metal ions, excelling as cation chelants especially in the field of radiopharmacy. The aim of this work is to characterize, by using the Time Differential Perturbed Angular Correlations (TDPAC) technique, the hyperfine interactions at hafnium sites in hafnium diethylenetriaminepentaacetate and to investigate their evolution as temperature increases. TDPAC results for KHfDTPA.3H{sub 2}O obtained by chemical synthesis yield a well defined and highly asymmetric interaction of quadrupole frequency ω{sub Q} = 141 Mrad/s, which is consistent with the existence of a unique site for the metal in the crystal lattice. The thermal behaviour of the chelate is investigated by means of differential scanning calorimetry and thermogravimetrical analyses revealing that an endothermic dehydration of KHfDTPA.3H{sub 2}O takes place in one step between 80 C and 180 C. The anhydrous KHfDTPA thus arising is characterized by a fully asymmetric and well defined interaction of quadrupole frequency ω{sub Q} = 168 Mrad/s. (orig.)

Thermal behaviour of hafnium diethylenetriaminepentaacetate studied using the perturbed angular correlation technique

International Nuclear Information System (INIS)

Chain, Cecilia Y.; Rivas, Patricia

2014-01-01

Polyaminecarboxilic ligands like diethylenetriaminepentaacetic acid form stable complexes with many heavy metal ions, excelling as cation chelants especially in the field of radiopharmacy. The aim of this work is to characterize, by using the Time Differential Perturbed Angular Correlations (TDPAC) technique, the hyperfine interactions at hafnium sites in hafnium diethylenetriaminepentaacetate and to investigate their evolution as temperature increases. TDPAC results for KHfDTPA.3H 2 O obtained by chemical synthesis yield a well defined and highly asymmetric interaction of quadrupole frequency ω Q = 141 Mrad/s, which is consistent with the existence of a unique site for the metal in the crystal lattice. The thermal behaviour of the chelate is investigated by means of differential scanning calorimetry and thermogravimetrical analyses revealing that an endothermic dehydration of KHfDTPA.3H 2 O takes place in one step between 80 C and 180 C. The anhydrous KHfDTPA thus arising is characterized by a fully asymmetric and well defined interaction of quadrupole frequency ω Q = 168 Mrad/s. (orig.)

Blood clearance and occupational exposure for {sup 177}Lu-DOTATATE compared to {sup 177}Lu-PSMA radionuclide therapy

Energy Technology Data Exchange (ETDEWEB)

Abuqbeitah, Mohammad; Demir, Mustafa; Uslu-Besli, Lebriz; Yeyin, Nami; Soenmezoglu, Kerim [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Faculty of Medicine, Istanbul (Turkey)

2018-03-15

The main target of this work is to examine blood clearance and external exposure for {sup 177}Lu-DOTATATE compared with new emerging {sup 177}Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5 ± 1.1 GBq {sup 177}Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq {sup 177}Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver's cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4-5 days and medical staff's dose was also estimated using electronic personal dosimeters. Finger dose was determined via ring TLD (Thermoluminescence Dosimeter) for radiopharmacists and nurses. Dose rates due to {sup 177}Lu-DOTATATE at a distance of 1 m, 4 h and 6 h after infusion, were 3.0 ± 2.8 and 2 ± 1.9 μSv/(h GBq), respectively, while those due to {sup 177}Lu-PSMA were 3.1 ± 0.8 and 2.2 ± 0.9 μSv/(h GBq). Total effective dose of 17 caregivers was 100-200 μSv for {sup 177}Lu-DOTATATE therapy. Mean effective doses to nurses and radiopharmacists were 5 and 4 μSv per patient, respectively, while those for physicists and physicians were 2 μSv per patient. For {sup 177}Lu-DOTATATE, effective half-life in blood and early elimination phase were 0.31 ± 0.13 and 4.5 ± 1 h, while they were found as 0.4 ± 0.1 and 5 ± 1 h, respectively, for {sup 177}Lu-PSMA. The first micturition time following {sup 177}Lu-DOTATATE infusion was noted after 36 ± 14 min, while the second and third voiding times were after 74 ± 9 and 128 ± 41 min, respectively. It is concluded that blood clearance and radiation exposure for {sup 177}Lu-DOTATATE are very similar to those for {sup 177}Lu-PSMA, and both treatment modalities are reasonably reliable for outpatient treatment, since the mean dose rate [2.1 μSv/(h GBq)] decreased below the dose rate that allows release of the patient

Studies on Optical and Electrical Properties of Hafnium Oxide Nanoparticles

Science.gov (United States)

Jayaraman, Venkatachalam; Sagadevan, Suresh; Sudhakar, Rajesh

2017-07-01

In this paper, the synthesis and physico-chemical properties of hafnium oxide nanoparticles (HfO2 NPs) are analyzed and reported. The synthesis was carried out by the precipitation route by using hafnium tetrachloride (HfCl4) as precursor material with potassium hydroxide (KOH) dissolved in Millipore water. In the precipitation technique, the chemical reaction is comparatively simple, low-cost and non-toxic compared to other synthetic methods. The synthesized HfO2 NPs were characterized by using powder x-ray diffraction (PXRD), ultraviolet-visible (UV-Vis) spectroscopy, Raman analysis, and high-resolution transmission electron microscopy (HRTEM). The monoclinic structure of the HfO2 NPs was resolved utilizing x-ray diffraction (XRD). The optical properties were studied from the UV-Vis absorption spectrum. The optical band gap of the HfO2NPs was observed to be 5.1 eV. The Raman spectrum shows the presence of HfO2 NPs. The HRTEM image showed that the HfO2 NPs were of spherical shape with an average particle size of around 28 nm. The energy-dispersive x-ray spectroscopy (EDS) spectrum obviously demonstrated the presence of HfO2 NPs. Analysis and studies on the dielectric properties of the HfO2 NPs such as the dielectric constant, the dielectric loss, and alternating current (AC) conductivity were carried out at varying frequencies and temperatures.

Rare-earth hafnium oxide materials for magnetohydrodynamic (MHD) generator application

Energy Technology Data Exchange (ETDEWEB)

Marchant, D. D; Bates, J. L.

1979-01-01

Several ceramic materials based on rare-earth hafnium oxides have been identified as potential high-temperature electrodes and low-temperature current leadouts for open cycle coal-fired MHD generator channels. The electrode-current leadouts combination must operate at temperatures between 400 and 2000K with an electrical conductivity greater than 10/sup -2/ ohm/sup -1/ cm/sup -1/. The electrodes will be exposed to flowing (linear flow rates up to 100 m/s) potassium seeded coal combustion gases (plasma core temperatures between 2400 to 3200/sup 0/K) and coal slag. During operation the electrodes must conduct direct electric current at densities near 1.5 amp/cm/sup 2/. Consequently, the electrodes must be resistant to electrochemical decompositions and interactions with both the coal slag and potassium salts (e.g., K/sub 2/SO/sub 4/, K/sub 2/CO/sub 3/). The current leadout materials are placed between the hot electrodes and the water-cooled copper structural members and must have electrical conductivities greater than 10/sup -2/ ohm/sup -1/ cm/sup -1/ between 1400 and 400/sup 0/K. The current leadouts must be thermally and electrochemically compatible with the electrode, copper, and potassium salts. Ideally, the electrodes and current leadouts should exhibit minimal ionic conductivity. The fabrication, electrical conductivity, and electrochemical corrosion of rare-earth hafnium oxide materials are discussed. (WHK)

Hafnium isotope evidence for a transition in the dynamics of continental growth 3.2 Gyr ago.

Science.gov (United States)

Næraa, T; Scherstén, A; Rosing, M T; Kemp, A I S; Hoffmann, J E; Kokfelt, T F; Whitehouse, M J

2012-05-30

Earth's lithosphere probably experienced an evolution towards the modern plate tectonic regime, owing to secular changes in mantle temperature. Radiogenic isotope variations are interpreted as evidence for the declining rates of continental crustal growth over time, with some estimates suggesting that over 70% of the present continental crustal reservoir was extracted by the end of the Archaean eon. Patterns of crustal growth and reworking in rocks younger than three billion years (Gyr) are thought to reflect the assembly and break-up of supercontinents by Wilson cycle processes and mark an important change in lithosphere dynamics. In southern West Greenland numerous studies have, however, argued for subduction settings and crust growth by arc accretion back to 3.8 Gyr ago, suggesting that modern-day tectonic regimes operated during the formation of the earliest crustal rock record. Here we report in situ uranium-lead, hafnium and oxygen isotope data from zircons of basement rocks in southern West Greenland across the critical time period during which modern-like tectonic regimes could have initiated. Our data show pronounced differences in the hafnium isotope-time patterns across this interval, requiring changes in the characteristics of the magmatic protolith. The observations suggest that 3.9-3.5-Gyr-old rocks differentiated from a >3.9-Gyr-old source reservoir with a chondritic to slightly depleted hafnium isotope composition. In contrast, rocks formed after 3.2 Gyr ago register the first additions of juvenile depleted material (that is, new mantle-derived crust) since 3.9 Gyr ago, and are characterized by striking shifts in hafnium isotope ratios similar to those shown by Phanerozoic subduction-related orogens. These data suggest a transitional period 3.5-3.2 Gyr ago from an ancient (3.9-3.5 Gyr old) crustal evolutionary regime unlike that of modern plate tectonics to a geodynamic setting after 3.2 Gyr ago that involved juvenile crust generation by plate

The interaction of fast neutrons with hafnium

International Nuclear Information System (INIS)

Smith, A.B.

2002-01-01

Elemental hafnium neutron total cross sections are measured from ∼0.75 to 4.5 MeV in steps of ∼40 keV. Differential neutron elastic-scattering cross sections are measured from ∼4.5 to 10.0 MeV in ∼0.5 MeV steps and at 40 scattering angles distributed between ∼17 and 160 deg. These data are combined with those found in the literature to construct a comprehensive experimental data base which is interpreted in terms of coupled-channels models. Physical characteristics of the resulting potentials are discussed. Comparisons are made with ENDF/B-6 (MAT 7200). A detailed report of this work is given by Smith (Smith, A., 2001. Argonne National Laboratory Report ANL/NDM-153)

Reinforcement against crack propagation of PWR absorbers by development of boron-carbon-hafnium composites

International Nuclear Information System (INIS)

Provot, B.; Herter, P.

2000-01-01

In order to improve the mechanical behaviour of materials used as neutron absorbers in nuclear reactors, we have developed CERCER or CERMET composites with boron and hafnium. Thus a new composite B 4 C/HfB 2 has been especially studied. We have identified three kinds of degradation under irradiation (thermal gradient, swelling due to fission products and accidental corrosion) that induce imposed deformations cracking phenomena. Mechanical behaviour and crack propagation resistance have been studied by ball-on-three-balls and double torsion tests. A special device was developed to enable crack propagation and associated stress intensity factor measurements. Effects of structure and of a second phase are underline. First results show that these materials present crack initiation and propagation resistance much higher than pure boron carbide or hafnium diboride. We observe R-Curves effects, crack bridging or branching, crack arrests, and toughness increases that we can relate respectively to the composite structures. (author)

Titrimetric determination of thiocyanate in solutions of the hafnium-zirconium separation process

International Nuclear Information System (INIS)

Vazquez, Cristina; Botbol, Moises; Hernandez, M.H.

1980-01-01

The control of the thiocyanate concentration is necessary during the process of separating hafnium from zirconium by the hexone-thiocyanate method. Said control is carried out by titrimetric determination of thiocyanate in aqueous and organic solutions containing hydrochloric acid and ammonium thiocyanate in presence or absence of zirconium and/or hafnium. The method consists in a redox volumetric analysis using a cerium (IV) salt as titrating agent, and ferroine as the final point indicator. Owing to the instability of thiocyanate in an acid medium it is necessary to know previously if the decomposition of solutions with different concentration of ammonium thiocyanate and hydrochloric acid may have an influence upon the analytic results or may even invalidate them. In order to obtain reliable results, it must be taken into account that the stability of the solutions depends on the thiocyanate concentration, the acidity and the time elapsed from the moment the sample is taken until the test is performed. The decomposition process can be slowed down by cooling the solutions. This method allows to control the plant and does not require any special equipment. (M.E.L) [es

Synthesis and characterization of hafnium oxide for luminescent applications

International Nuclear Information System (INIS)

Guzman Mendoza, J.; Aguilar Frutis, M.A.; Flores, G. Alarcon; Garcia Hipolito, M.; Azorin Nieto, J.; Rivera Montalvo, T.; Falcony, C.

2008-01-01

Full text: Hafnium oxide (HfO 2 ) is a material with a wide range of possible technological applications because it's chemical and physical properties such as high melting point, high chemical stability, high refraction index, high dielectric constant and hardness near to diamond in the tetragonal phase. The large energy gap and low phonon frequencies of the HfO 2 makes it appropriate as a host matrix for been doped with rare earth activators. Efficient luminescent materials find wide application in electroluminescent flat panel displays; color plasma displays panels, scintillators, cathode ray tubes, fluorescent lamps, lasers, etc. In recent years the study of luminescent materials based on HfO 2 has been intensified. Some groups have studied the optical properties of doped and undoped HfO 2 . In this contribution, Hafnium Oxide (HfO 2 ) films were prepared using the spray pyrolysis deposition technique. The material was synthesized using chlorides as raw materials in deionised water as solvent and deposited on Corning glass substrates at temperatures from 300 deg C to 600 deg C. For substrate temperatures lower than 400 deg C, the deposited films are amorphous, while for substrate temperatures higher than 450 deg C, the monoclinic phase of HfO 2 appears. Scanning electron microscopy with microprobe analysis was use to observe the microstructure and obtain the chemical composition of the films; rough surfaces with spherical particles were appreciated. UV and low energy X Ray radiations were used in order to achieve the thermoluminescent characterization of the films as a function of the deposition temperature

21 CFR 177.2430 - Polyether resins, chlorinated.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyether resins, chlorinated. 177.2430 Section 177... Components of Articles Intended for Repeated Use § 177.2430 Polyether resins, chlorinated. Chlorinated polyether resins may be safely used as articles or components of articles intended for repeated use in...

21 CFR 177.1810 - Styrene block polymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Styrene block polymers. 177.1810 Section 177.1810... FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1810 Styrene block polymers. The styrene...

Titanium, zirconium- and hafnium containing initiators in the polymerization of acrylic monomers to ''living'' polymers

International Nuclear Information System (INIS)

Farnham, W.B.; Hertler, W.R.

1988-01-01

This patent describes a process for preparing ''living'' polymer. The process comprises contacting one or more acrylic monomers under polymerizing conditions with a polymerization-initiating amount of a tetra-coordinate organotitanium, organozirconium or organo-hafnium polymerization initiator, and ''living'' polymers produced thereby

Zirconium and hafnium tetrachloride separation by extractive distillation with molten zinc chloride lead chloride solvent

International Nuclear Information System (INIS)

McLaughlin, D.F.; Stoltz, R.A.

1988-01-01

In an extractive distillation method for separating hafniuim tetrachloride from zirconium tetrachloride of the type wherein a mixture of zirconium and hafnium tetrachlorides is introduced into an extractive distillation column, which extractive distillation column has a reboiler connected at the bottom and a reflux condenser connected at the top and wherein a molten salt solvent is circulated into the reflux condenser and through the column to provide a liquid phase, and wherein molten salt solvent containing zirconium tetrachloride is taken from the reboiler and run through a stripper to remove zirconium tetrachloride product from the molten salt solvent and the stripped molten salt solvent is returned to the reflux condenser and hafnium tetrachloride enriched vapor is taken as product from the reflux condenser, the improvement is described comprising: the molten salt having a composition of at least 30 mole percent zinc chloride and at least 10 mole percent of lead chloride

49 CFR 177.843 - Contamination of vehicles.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Contamination of vehicles. 177.843 Section 177.843... and Unloading § 177.843 Contamination of vehicles. (a) Each motor vehicle used for transporting Class... surface contamination is not greater than the level prescribed in § 173.443(a) of this subchapter. (b...

21 CFR 177.2550 - Reverse osmosis membranes.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Reverse osmosis membranes. 177.2550 Section 177... Components of Articles Intended for Repeated Use § 177.2550 Reverse osmosis membranes. Substances identified in paragraph (a) of this section may be safely used as reverse osmosis membranes intended for use in...

Atomic layer deposition of calcium oxide and calcium hafnium oxide films using calcium cyclopentadienyl precursor

International Nuclear Information System (INIS)

Kukli, Kaupo; Ritala, Mikko; Sajavaara, Timo; Haenninen, Timo; Leskelae, Markku

2006-01-01

Calcium oxide and calcium hafnium oxide thin films were grown by atomic layer deposition on borosilicate glass and silicon substrates in the temperature range of 205-300 o C. The calcium oxide films were grown from novel calcium cyclopentadienyl precursor and water. Calcium oxide films possessed refractive index 1.75-1.80. Calcium oxide films grown without Al 2 O 3 capping layer occurred hygroscopic and converted to Ca(OH) 2 after exposure to air. As-deposited CaO films were (200)-oriented. CaO covered with Al 2 O 3 capping layers contained relatively low amounts of hydrogen and re-oriented into (111) direction upon annealing at 900 o C. In order to examine the application of CaO in high-permittivity dielectric layers, mixtures of Ca and Hf oxides were grown by alternate CaO and HfO 2 growth cycles at 230 and 300 o C. HfCl 4 was used as a hafnium precursor. When grown at 230 o C, the films were amorphous with equal amounts of Ca and Hf constituents (15 at.%). These films crystallized upon annealing at 750 o C, showing X-ray diffraction peaks characteristic of hafnium-rich phases such as Ca 2 Hf 7 O 16 or Ca 6 Hf 19 O 44 . At 300 o C, the relative Ca content remained below 8 at.%. The crystallized phase well matched with rhombohedral Ca 2 Hf 7 O 16 . The dielectric films grown on Si(100) substrates possessed effective permittivity values in the range of 12.8-14.2

21 CFR 177.2910 - Ultra-filtration membranes.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ultra-filtration membranes. 177.2910 Section 177... Components of Articles Intended for Repeated Use § 177.2910 Ultra-filtration membranes. Ultra-filtration membranes identified in paragraphs (a)(1), (a)(2), (a)(3), and (a)(4) of this section may be safely used in...

21 CFR 177.1670 - Polyvinyl alcohol film.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyvinyl alcohol film. 177.1670 Section 177.1670... Components of Single and Repeated Use Food Contact Surfaces § 177.1670 Polyvinyl alcohol film. Polyvinyl alcohol film may be safely used in contact with food of the types identified in § 176.170(c) of this...

Separation of zirconium--hafnium by nitride precipitation

International Nuclear Information System (INIS)

Anderson, R.N.; Parlee, N.A.

1977-01-01

A method is described for the separation of a light reactive metal (e.g., zirconium) from a heavy reactive metal (e.g., hafnium) by forming insoluble nitrides of the metals in a molten metal solvent (e.g., copper) inert to nitrogen and having a suitable density for the light metal nitride to form a separate phase in the upper portion of the solvent and for the heavy metal nitride to form a separate phase in the lower portion of the solvent. Nitriding is performed by maintaining a nitrogen-containing atmosphere over the bath. The light and heavy metals may be an oxide mixture and carbothermically reduced to metal form in the same bath used for nitriding. The nitrides are then separately removed and decomposed to form the desired separate metals. 16 claims, 1 figure

Modified method for zirconium or hafnium gravimetric determination with glycolic acid derivatives

International Nuclear Information System (INIS)

Barbieri, R.S.; Rocha, J.C.; Terra, V.R.; Marques Neto, A.

1989-01-01

The conditions for gravimetric determination of zirconium or hafnium by glicolic acid derivatives were studied by thermogravimetric analysis. The method utilized shown that after precipitation, washing and drying of precipitates at 150 0 C, the resulting solid was weighed in the form of [M{RCH(OH)COO} 4 ] (M = Zr,Hf;R = C 6 H 5 , β-C 10 H 7 ,p-BrC 6 H 4 ). (author) [pt

On-line separation of refractory hafnium and tantalum isotopes at the ISOCELE separator

CERN Document Server

Liang, C F; Obert, J; Paris, P; Putaux, J C

1981-01-01

By chemical evaporation technique, neutron deficient hafnium nuclei have been on-line separated at the ISOCELE facility, from the isobar rare-earth elements, in the metal-fluoride HfF/sub 3//sup +/ ion form. Half-lives of /sup 162-165/Hf have been measured. Similarly, tantalum has been selectively separated on the TaF/sub 4//sup +/ form. (4 refs) .

Self-cleaning and surface chemical reactions during hafnium dioxide atomic layer deposition on indium arsenide.

Science.gov (United States)

Timm, Rainer; Head, Ashley R; Yngman, Sofie; Knutsson, Johan V; Hjort, Martin; McKibbin, Sarah R; Troian, Andrea; Persson, Olof; Urpelainen, Samuli; Knudsen, Jan; Schnadt, Joachim; Mikkelsen, Anders

2018-04-12

Atomic layer deposition (ALD) enables the ultrathin high-quality oxide layers that are central to all modern metal-oxide-semiconductor circuits. Crucial to achieving superior device performance are the chemical reactions during the first deposition cycle, which could ultimately result in atomic-scale perfection of the semiconductor-oxide interface. Here, we directly observe the chemical reactions at the surface during the first cycle of hafnium dioxide deposition on indium arsenide under realistic synthesis conditions using photoelectron spectroscopy. We find that the widely used ligand exchange model of the ALD process for the removal of native oxide on the semiconductor and the simultaneous formation of the first hafnium dioxide layer must be significantly revised. Our study provides substantial evidence that the efficiency of the self-cleaning process and the quality of the resulting semiconductor-oxide interface can be controlled by the molecular adsorption process of the ALD precursors, rather than the subsequent oxide formation.

Ground-state structures of Hafnium clusters

Energy Technology Data Exchange (ETDEWEB)

Ng, Wei Chun; Yoon, Tiem Leong [School of Physics, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia); Lim, Thong Leng [Faculty of Engineering and Technoloty, Multimedia University, Melaca Campus, 75450 Melaka (Malaysia)

2015-04-24

Hafnium (Hf) is a very large tetra-valence d-block element which is able to form relatively long covalent bond. Researchers are interested to search for substitution to silicon in the semi-conductor industry. We attempt to obtain the ground-state structures of small Hf clusters at both empirical and density-functional theory (DFT) levels. For calculations at the empirical level, charge-optimized many-body functional potential (COMB) is used. The lowest-energy structures are obtained via a novel global-minimum search algorithm known as parallel tempering Monte-Carlo Basin-Hopping and Genetic Algorithm (PTMBHGA). The virtue of using COMB potential for Hf cluster calculation lies in the fact that by including the charge optimization at the valence shells, we can encourage the formation of proper bond hybridization, and thus getting the correct bond order. The obtained structures are further optimized using DFT to ensure a close proximity to the ground-state.

Molecular structure, vibrational, HOMO-LUMO, MEP and NBO analysis of hafnium selenite

Science.gov (United States)

Yankova, Rumyana; Genieva, Svetlana; Dimitrova, Ginka

2017-08-01

In hydrothermal condition hafnium selenite with estimated chemical composition Hf(SeO3)2·n(H2O) was obtained and characterized by powder X-Ray diffraction, IR spectroscopy and thermogravimetrical analysis. The composition of the obtained crystalline phase was established as dihydrate of tetraaqua complex of the hafnium selenite [Hf(SeO3)2(H2O)4]·2H2O. The results of the thermogravimetrical analysis are shown that the two hydrated water molecules are released in the temperature interval 80-110°C, while the four coordinated water molecules - at 210-300°C. By DFT method, with Becke's three parameter exchange-functional combined with gradient-corrected correlation functional of Lee, Yang and Parr and 6-31G(d), 6-311 + G(d,p) basis sets and LANL2DZ for Hf atom were calculated the molecular structure, vibrational frequencies and thermodynamic properties of the structure. The UV-Vis spectra and electronic properties are presented. The energy and oscillator strength calculated by time-dependent density functional theory corresponds well with the experimental ones. Molecular electrostatic potential (MEP) was performed. Mulliken population analysis on atomic charges was also calculated. The stability and intramolecular interactions are interpreted by NBO analysis.

Near net shape processing of zirconium or hafnium metals and alloys

International Nuclear Information System (INIS)

Evans, S.C.

1992-01-01

This patent describes a process for producing a metal shape. It comprises: plasma arc melting a metal selected from zirconium, hafnium and alloys thereof comprising at least about 90 w/o of these metals to form a liquid pool; pouring the metal form the pool into a mold to form a near net shape; and reducing the metal from its near net shape to a final size while maintaining the metal temperature below the alpha-beta transition temperature throughout the size reducing step

In-Pile Experiment of a New Hafnium Aluminide Composite Material to Enable Fast Neutron Testing in the Advanced Test Reactor

Energy Technology Data Exchange (ETDEWEB)

Donna Post Guillen; Douglas L. Porter; James R. Parry; Heng Ban

2010-06-01

A new hafnium aluminide composite material is being developed as a key component in a Boosted Fast Flux Loop (BFFL) system designed to provide fast neutron flux test capability in the Advanced Test Reactor. An absorber block comprised of hafnium aluminide (Al3Hf) particles (~23% by volume) dispersed in an aluminum matrix can absorb thermal neutrons and transfer heat from the experiment to pressurized water cooling channels. However, the thermophysical properties, such as thermal conductivity, of this material and the effect of irradiation are not known. This paper describes the design of an in-pile experiment to obtain such data to enable design and optimization of the BFFL neutron filter.

Dicty_cDB: CHF177 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available CH (Link to library) CHF177 (Link to dictyBase) - - - Contig-U11892-1 - (Link to Or...iginal site) - - CHF177Z 395 - - - - Show CHF177 Library CH (Link to library) Clone ID CHF177 (Link to dicty...Base) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U11892-1 Original site URL http://dictycdb.b...LLLWDVQGFPCXFAVEG GQCIDPSSLKVGGKYSFIAFSTCRXKFDNQKIHDCDWIIQGPTTPSXCANCGKICTSKCT TNYCDRDXQT Translated Amino A...XKFDNQKIHDCDWIIQGPTTPSXCANCGKICTSKCT TNYCDRDXQT Homology vs CSM-cDNA Score E Sequences producing significant

Complexing of zirconium and hafnium with ortho-aminobenzoic acid and paraaminobenzoic acid

International Nuclear Information System (INIS)

Alekseeva, I.I.; Nemzer, I.I.; Yuranova, L.I.; Borisova, V.V.; Prozorovskaya, Z.N.

1977-01-01

Formation of complexes between zirconium and hafnium and ortho- and para-aminobenzoic acids has been studied by the kinetic method. It has been found that at pH=1.3-2.0 and concentrations of metals 10 -5 -10 -6 mole complex compounds are formed with composition Me:L=1:2 and 1:1 (Me=Zr, Hf; L=ortho- or para-aminobenzoic acids). Stepwise constants and overall effective constants of complex formation have been calculated

The Bad Berka dose protocol: comparative results of dosimetry in peptide receptor radionuclide therapy using (177)Lu-DOTATATE, (177)Lu-DOTANOC, and (177)Lu-DOTATOC.

Science.gov (United States)

Schuchardt, Christiane; Kulkarni, Harshad R; Prasad, Vikas; Zachert, Carolin; Müller, Dirk; Baum, Richard P

2013-01-01

The objective of this study is to analyze the in vivo behavior of the (177)Lu-labeled peptides DOTATATE, DOTANOC, and DOTATOC used for peptide receptor radionuclide therapy (PRRNT) of neuroendocrine tumors (NETs), by measuring organ and tumor kinetics and by performing dosimetric calculations. Two hundred fifty-three patients (group 1) with metastasized NET who underwent PRRNT were examined. Out of these, 185 patients received (177)Lu-DOTATATE, 9 were treated with (177)Lu-DOTANOC, and 59 with (177)Lu-DOTATOC. Additionally, 25 patients receiving, in consecutive PRRNT cycles, DOTATATE followed by DOTATOC (group 2) and 3 patients receiving DOTATATE and DOTANOC (group 3) were analyzed. Dosimetric calculations (according to MIRD scheme) were performed using OLINDA software. In group 1, DOTATOC exhibited the lowest and DOTANOC the highest uptake and therefore mean absorbed dose in normal organs (whole body, kidney, and spleen). In group 2, there was a significant difference between DOTATATE and DOTATOC concerning kinetics and normal organ doses. (177)Lu-DOTATOC had the lowest uptake/dose delivered to normal organs and highest tumor-to-kidney ratio. There were no significant differences between the three peptides concerning tumor kinetics and mean absorbed tumor dose. The study demonstrates a correlation between high affinity of DOTANOC in vitro and high uptake in normal organs/whole body in vivo, resulting in a higher whole-body dose. DOTATOC exhibited the lowest uptake and dose delivered to normal tissues and the best tumor-to-kidney ratio. Due to large interpatient variability, individual dosimetry should be performed for each therapy cycle.

High temperature thermodynamics of solutions of oxygen in zirconium and hafnium

International Nuclear Information System (INIS)

Boureau, G.; Gerdanian, P.

1984-01-01

The Tian-Calvet microcalorimetric method has been applied to the determination at 1323 Kelvin of ΔH(O 2 ), the partial molar enthalpy of mixing of oxygen in zirconium and in hafnium. No measurable departure from Henry's law has been found for dilute solutions (ratio oxygen over metal smaller than 0.1). For concentrated solutions repulsive interactions are found in agreement with the existence of ordered structures at lower temperatures. The domain of homogeneity of zirconium has been found larger than previously assumed. (author)

27 CFR 20.177 - Encased containers.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Encased containers. 20.177... Users of Specially Denatured Spirits Operations by Dealers § 20.177 Encased containers. (a) A dealer may package specially denatured spirits in unlabeled containers which are completely encased in wood...

19 CFR 177.4 - Oral discussion of issues.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Oral discussion of issues. 177.4 Section 177.4... TREASURY (CONTINUED) ADMINISTRATIVE RULINGS General Ruling Procedure § 177.4 Oral discussion of issues. (a... issue or issues involved should indicate that desire in writing at the time the ruling request is filed...

21 CFR 177.1555 - Polyarylate resins.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyarylate resins. 177.1555 Section 177.1555 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... in contact with all foods except beverages containing more than 8 volume percent ethanol under...

46 CFR 177.940 - Guards in vehicle spaces.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Guards in vehicle spaces. 177.940 Section 177.940... TONS) CONSTRUCTION AND ARRANGEMENT Rails and Guards § 177.940 Guards in vehicle spaces. On a vessel authorized to carry one or more vehicles, suitable chains, cables, or other barriers must be installed at the...

19 CFR 177.27 - Oral discussion of issues.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Oral discussion of issues. 177.27 Section 177.27....27 Oral discussion of issues. Any party authorized to request a ruling under the provisions of § 177.23 may request an opportunity for oral discussion of the issues presented in the request. The oral...

Extraction of hafnium by 1-phenyl-3-methyl-4-benzoyl-5-pyralozone from aqueous-alcoholic solutions

International Nuclear Information System (INIS)

Hala, J.; Prihoda, J.

1975-01-01

Extraction of hafnium by 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (HL) in benzene, toluene, chloroform and tetrachloromethane from aqueous-alcoholic solutions of the formal acidity of 2M-HClO 4 was studied. Methyl, ethyl, n- and isopropyl, tert-butyl and allyl alcohol as well as ethylene glycol monomethyl ether and propylene glycol were used as organic components of the mixed aqueous-organic phase. Their presence in some cases resulted in a synergic increase in the distribution ratio of hafnium. The increase is interpreted using the results of a slope analysis and measurements of the alcohol distribution and the relative permittivity of the organic phase. It is suggested that HfL 4 molecules were solvated by alcohol molecules in the organic phase. At high alcohol concentration synergism changed into antagonism. This was caused by changes in the distribution of HL and its interaction with the alcohol in the organic phase. (author)

Trap state passivation improved hot-carrier instability by zirconium-doping in hafnium oxide in a nanoscale n-metal-oxide semiconductor-field effect transistors with high-k/metal gate

International Nuclear Information System (INIS)

Liu, Hsi-Wen; Tsai, Jyun-Yu; Liu, Kuan-Ju; Lu, Ying-Hsin; Chang, Ting-Chang; Chen, Ching-En; Tseng, Tseung-Yuen; Lin, Chien-Yu; Cheng, Osbert; Huang, Cheng-Tung; Ye, Yi-Han

2016-01-01

This work investigates the effect on hot carrier degradation (HCD) of doping zirconium into the hafnium oxide high-k layer in the nanoscale high-k/metal gate n-channel metal-oxide-semiconductor field-effect-transistors. Previous n-metal-oxide semiconductor-field effect transistor studies demonstrated that zirconium-doped hafnium oxide reduces charge trapping and improves positive bias temperature instability. In this work, a clear reduction in HCD is observed with zirconium-doped hafnium oxide because channel hot electron (CHE) trapping in pre-existing high-k bulk defects is the main degradation mechanism. However, this reduced HCD became ineffective at ultra-low temperature, since CHE traps in the deeper bulk defects at ultra-low temperature, while zirconium-doping only passivates shallow bulk defects.

Determination of hafnium with the inductively coupled plasma (ICP)

International Nuclear Information System (INIS)

Wuensch, G.; Pose, K.

1985-01-01

The relative intensities of 198 hafnium lines in the Ar-ICP are listed. Spectral interference tables are given for the 9 analytically best lines, covering the range of +-60 pm around the Hf-lines. They include measured (not calculated) data of the interferent equivalent concentrations (IEC) and the critical concentration ratios (CCR) for 115 lines of all 34 possibly interfering elements. In many cases, these IEC- or CCR-data differ by 1 or 2 orders of magnitude from those calculated from intensities observed in the NBS-copper arc. Since no intense Hf-line is free from spectral interferences, examples are given for the calculation of the most suitable line for a known matrix. (orig.) [de

40 CFR 264.177 - Special requirements for incompatible wastes.

Science.gov (United States)

2010-07-01

... DISPOSAL FACILITIES Use and Management of Containers § 264.177 Special requirements for incompatible wastes... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Special requirements for incompatible wastes. 264.177 Section 264.177 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

Atom-vacancy ordering and magnetic susceptibility of nonstoichiometric hafnium carbide

International Nuclear Information System (INIS)

Gusev, A.I.; Zyryanova, A.N.

1999-01-01

Experimental results on magnetic susceptibility of nonstoichiometric hafnium carbide HfC y (0.6 0.71 , HfC 0.78 and HfC 0.83 in the range of 870-930 K the anomalies are revealed which are associated with superstructure short-range ordering in a non-metallics sublattice. It is shown that a short-range order in HfC 0.71 and HfC 0.78 carbides corresponds to Hf 3 C 2 ordered phase, and in HfC 0.83 carbide - to Hf 6 C 5 ordered phase. HfC 0.78 carbide is found to possesses zero magnetic susceptibility in temperature range 910-980 K [ru

Dosimetric Studies in Normal Mice of 177Lu-DOTA-SP and 177Lu-DOTA-His2-MG

International Nuclear Information System (INIS)

Puerta Yepes, N.; Rojo, A.M.; Lopez Bularte, A.C.; Nevares, N.; Zapata, M.; Perez, J.H.; Crudo, J.

2010-01-01

DOTA-Substance-P (SP) and DOTA-minigastrin (His2-MG) labeled with 177 Lu could be used in peptide receptor radionuclide therapy (PRRT) for treatment of various tumour species. Biodistribution studies of both radiopharmaceuticals in normal mice were performed at different times. Absorbed doses in mouse organs were estimated and extrapolated to humans. Dosimetric calculations showed that kidneys received the highest dose, for both radiopharmaceuticals. The Maximum Tolerated Activity (MTA) of 177 Lu-DOTA-SP that can be administered without kidney toxicity are 414 and 422 MBq/kg for the standard adult man and woman, respectively. In the same way, the MTA of 177 Lu-DOTA-His2-MG are 488 and 518 MBq/kg for the standard adult man and woman, respectively. (authors)

Hafnium carbide nanocrystal chains for field emitters

International Nuclear Information System (INIS)

Tian, Song; Li, Hejun; Zhang, Yulei; Ren, Jincui; Qiang, Xinfa; Zhang, Shouyang

2014-01-01

A hafnium carbide (HfC) nanostructure, i.e., HfC nanocrystal chain, was synthesized by a chemical vapor deposition (CVD) method. X-ray diffractometer, field-emission scanning electron microscope, transmission electron microscope, and energy-dispersive X-ray spectrometer were employed to characterize the product. The synthesized one-dimensional (1D) nanostructures with many faceted octahedral nanocrystals possess diameters of tens of nanometers to 500 nm and lengths of a few microns. The chain-like structures possess a single crystalline structure and preferential growth direction along the [1 0 0] crystal orientation. The growth of the chains occurred through the vapor–liquid–solid process along with a negative-feedback mechanism. The field emission (FE) properties of the HfC nanocrystal chains as the cold cathode emitters were examined. The HfC nanocrystal chains display good FE properties with a low turn-on field of about 3.9 V μm −1 and a high field enhancement factor of 2157, implying potential applications in vacuum microelectronics.

Simplified method for gravimetric determination of zirconium or hafnium with α-hydroxy carboxylic acids

International Nuclear Information System (INIS)

Barbieri, R.S.; Rocha, J.C.; Terra, V.R.; Marques Netto, A.

1989-01-01

The conditions for gravimetric determination of zirconium or hafnium by glicoloc acids derivatives were studied by thermogravimetric analysis. The method utilized shownd that after precipitation, washing and drying of precipitates at 150 o C, the resulting solid was weighed in the form of [M (RCH(OH)COO) 4 ] (M = Zr, Hf; R + C 6 H 5 , β-C 10 H 7 , p-BrC 6 H 4 ). (author)

Complexonometric determination of hafnium (4) in the presence of europium(3) or tantalum(5)

International Nuclear Information System (INIS)

Oziashvili, E.D.; Ehsakiya, K.E.; Sirakanyan, N.M.

1986-01-01

Complexonometric determination of hafnium in the presence of Ta or Eu in samples which can be decomposed by acids, i.e. in double borides has been investigated. Initial solutions are prepared by fusing with K 2 S 2 O 8 excess, the fusion was leached by hot water, H 2 SO L 4 was added and Hf was titrated by complexone 3 in the presence of xylenol orange

Investigation of interaction of zirconium and hafnium tetrafluorides with strontium fluoride

International Nuclear Information System (INIS)

Ratnikova, I.D.; Korenev, Yu.M.; Novoselova, A.V.

1980-01-01

Diagrams of the condensated state of systems SrF 2 -EF 4 have been plotted, where E represents Zr, Hf. In these systems, three intermediate compounds of Sr 3 EF 10 , Sr 2 EF 8 and Sr EF 6 compositions are formed. All those compounds melt incongruently at temperatures of 982, 865 and 750 deg C, respectively - zirconium salt; at temperatures of 1000, 900 and 820 deg C - hafnium salts. Fluoro-metallates of composition 2:1, and 1:1, exist in two polymorphic forms. Tetrafluorides were found to dissolve in strontium fluoride: they form solid solutions having fluorite structure

Comparison of tumour and whole body absorbed doses of 177-Lu-DOTA-TATE and Lu-177-DOTA-NOC treatment in the same patient group

International Nuclear Information System (INIS)

Yeyin, N.; Kabasakal, L.; Akyel, R.; Demir, M.; Kanmaz, B.; Ocak, M.; Toklu, T.; Selcuk, N.

2015-01-01

Full text of publication follows. Peptide Receptor Radionuclide Therapy (PRRT) with Lu-177 labelled peptides in patients with neuroendocrine tumours (NETs) aroused great interest. An estimation of actual radiation doses to tumours is very important for therapy planning. There are several radiolabelled peptides, which can be used for PRRT with different biological behaviour. Aim: the aim of the study was to compare the tumour and normal organ absorbed doses in patients who have received Lu-177-DOTA-TATE and Lu-177 DOTA-NOC. Materials and methods: study was composed of 20 patients (M/F: 10/10, mean age: 51.5 ± 14.9) with histologically proven inoperable NETs. All patients received Lu-177-DOTA-NOC treatment 6 to 12 weeks after last Lu-177-DOTA-TATE treatment. Dosimetric calculations were performed using MIRD scheme and lesion doses were calculated using post therapy whole body images obtained at 4, 20, 44, and 68 hours after injection. Tumour volumes were determined from CT images. Thirteen blood samples beginning from time zero to 4 days after injection were obtained for bone marrow and whole body dosimetry. Results: There were 53 lesions in Lu-177-DOTA-TATE post-therapy whole body images and 49 lesions in Lu-177 DOTA-NOC post therapy images. Lesions were selected according to lesion delineation and superimposed lesions were excluded. Mean lesion absorbed dose is calculated to be 47.4 ± 53.4 and 42.9 ± 52.8 Gy per 370 MBq for Lu-177-DOTA-TATE and DOTA-NOC respectively (p>0.5). There were significantly higher absorbed doses for kidney and bone marrow after Lu-177-DOTA-NOC treatment as compared to Lu-177-DOTA-TATE treatment, which were 6.9 ± 2.7 vs 3.9 ± 1.7 (p<0.05) and 0.12 ± 0.0 vs 0.10 ± 0.0 (p<0.05) Gy, respectively. There was not any difference in plasma elimination times between two tracers. On the other hand the whole body absorbed dose was significantly higher after Lu-177-DOTA-NOC treatment, which was 0.24 ± 0.07 vs 0.20 ± 0.06 Gy (p<0

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

Science.gov (United States)

Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

2011-01-01

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

Science.gov (United States)

Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

2017-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Laser coating of hafnium on Ti6Al4 for biomedical applications

CSIR Research Space (South Africa)

Phume, L

2012-12-01

Full Text Available Al4V FOR BIOMEDICAL APPLICATIONS Lerato Phume 1, 2, S.L. Pityana 1, 2, C. Meacock 1, A.P.I Popoola 2 1. National Laser Centre, Council for Scientific and Industrial Research, P.O. Box 395, Pretoria, 0001, South Africa 2. Department of Chemical... and Metallurgical Engineering, Tshwane University of Technology, Private Bag X 680, Pretoria, 0001, South Africa (b) (c) (e) To investigate laser surface coating of Ti6Al4V with preplaced Hafnium powder, to determine the influence of the energy density...

Preparation, structure and properties of hafnium compounds in the system Hf-C-N-O

International Nuclear Information System (INIS)

Brundiers, G.D.

1975-08-01

Highly dense, homogenous and single phase hafnium carbonitride samples (with low oxygen content) were prepared in the whole concentration range of the ternary cubic carbonitrides. Stoichiometric hafnium oxicarbides were also prepared within the range of solubility. The procedure involved the hot pressing of powders of HfC, HfN, Hf, Hf-Oxide and carbon at temperatures of 3,000 0 C and pressures up to 550 kpf/cm 2 using a novel technique. Small single crystals of slightly substoichiometric HfN were also repared. The densification of the powders was studied as a function of the non-metal concentration. Carbonitrides with N/Hf ratio of 0.37 were prepared in a high temperature autoclave operating at medium pressures by the reaction of HfC with nitrogen. All the samples were characterized by density measurements, chemical, X-ray and metallographic analysis and in some cases with the aid of quantitative metallography and microprobe analysis. Typical properties investigated were lattice parameter, thermal expansion, microhardness and electrical resistivity as function of the non-metal content. For specific concentrations extreme values in the properties are attained. With the aid of the valence electron concentration (VEC) parameter, the properties can be correlated with the density of states of electrons at the Fermi level. (orig./HK) [de

Alternative method to determine Specific Activity of (177)Lu by HPLC.

Science.gov (United States)

Breeman, Wouter A P; de Zanger, Rory M S; Chan, Ho Sze; de Blois, Erik

2015-01-01

Peptide Receptor Radionuclide Therapy (PRRT) with (177)Lu-DOTA-peptides requires (177)Lu with high specific activity (SA) and values >740 GBq (177)Lu per mg Lu to maximise the atom% of (177)Lu over total Lu. Vendors provide SA values which are based on activity and mass of the target, whereas due to "burn-up" of target, these SA values are not accurate. For a radiochemist the SA of (177)Lu is of interest prior to radiolabeling. An alternative method to determine SA was developed by HPLC, which includes a metal titration of a known amount of DOTA-peptide with a known amount of activity ((177)Lu), and a unknown amount of metal ((177+nat)Lu). Based on an HPLC separation of radiometal-DOTA-peptide and DOTA-peptide, and the concordant ratio of these components the metal content ((177+nat)Lu) can be calculated, and eventually the SA of (177)Lu can be accurately determined. These experimentally determined SA values exceeded the estimated values provided by vendors by 27 ± 16%, (range 6-73 %). The deviation of SA values for samples from the same Lu batch was <2% (n ≥ 10). the SA of (177)Lu is apparently often higher as stated by vendors in comparison to the experimentally determined actual values. For this reason, the SA of (177)Lu-DOTA-TATE and other Lu-DOTA-peptides could be increased accordingly.

Production of 177Lu for targeted radionuclide therapy: Available options

International Nuclear Information System (INIS)

Dah, Ashutosh; Pillai, Maroor Raghavan Ambikalmajan; Knapp, Furn F. Jr.

2015-01-01

This review provides a comprehensive summary of the production of 177 Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of 177 Lu having the required quality for preparation of a variety of 177 Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of 177 Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. While both “direct” and “indirect” reactor production routes offer the possibility for sustainable 177 Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. A broad understanding and discussion of the issues associated with 177 Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of 177 Lu-labeled radiopharmaceuticals, but also help future developments

19 CFR 177.13 - Inconsistent customs decisions.

Science.gov (United States)

2010-04-01

... inconsistent with decisions being made by Customs officials at another location may be brought to the attention...) Inconsistent decisions subject to petition. The decisions which may be the subject of a petition include: (i... 19 Customs Duties 2 2010-04-01 2010-04-01 false Inconsistent customs decisions. 177.13 Section 177...

Lutetium-177-EDTMP for pain palliation in bone metastases

International Nuclear Information System (INIS)

Rutty Sola, Gisela A.; Arguelles, Maria G.; Bottazzini, Debora L.; Furnari, Juan C.; Vera Ruiz, H.

1999-01-01

Experiences with the new palliative agent Lu-177 EDTMP are summarized. The production of primary 177 Lu by the 176 Lu(n,γ) 177 Lu reaction and the synthesis of the radioactive complex are described as well as the procedures used for the control of the radionuclidic and the radiochemical purity. The stability of the compound has been also studied. The in vivo essays with rats and the use of the radiopharmaceutical, after a careful dose evaluation, in a patient with bone metastases from a breast cancer, show that the behaviour of Lu-177 EDTMP is similar to that of the analogue Sm-153 EDTMP. (author)

High spin K isomeric target of 177mLu

International Nuclear Information System (INIS)

Roig, O.; Belier, G.; Daugas, J.-M.; Delbourgo, P.; Maunoury, L.; Meot, V.; Morichon, E.; Sauvestre, J.-E.; Aupiais, J.; Boulin, Y.; Fioni, G.; Letourneau, A.; Marie, F.; Ridikas, D.

2004-01-01

The techniques used to produce a 177m Lu (J π =23/2 - ,T 1/2 =160.4 days) target are described in this paper. Firstly, an isotopic separation of an enriched lutetium sample was used to reach a purity of 176 Lu close to 99.993%. Afterwards, the high neutron flux of the Grenoble Institut Laue-Langevin reactor was used to produce the 177m Lu isomer by the 176 Lu(n,γ) reaction. Finally, a chemical separation was performed to extract 10 13 nuclei of 177m Lu. Thanks to this experiment, we have been able to estimate the destruction cross-section of the 177m Lu

Hafnium isotope ratios of nine GSJ reference samples

International Nuclear Information System (INIS)

Hanyu, Takeshi; Nakai, Shun'ichi; Tatsuta, Riichiro

2005-01-01

176 Hf/ 177 Hf ratios of nine geochemical reference rocks from the Geological Survey of Japan, together with BIR-1 and BCR-2, were determined using multi-collector inductively coupled plasma mass spectrometry. Our data for BIR-1, BCR-2 and JB-1 are in agreement with those previously reported, demonstrating the appropriateness of the chemical procedure and isotopic measurement employed in this study. The reference rocks have a wide range of 176 Hf/ 177 Hf covering the field defined by various volcanic rocks, such as mid-ocean ridge basalts, ocean island basalts, and subduction related volcanic rocks. They are therefore suitable as rock standards for Hf isotope measurement of geological samples. (author)

Highly substituted zirconium and hafnium cyclopentadienyl bifunctional β-diketiminate complexes – Synthesis, structure, and catalytic activity towards ethylene polymerization

Czech Academy of Sciences Publication Activity Database

Havlík, A.; Lamač, Martin; Pinkas, Jiří; Varga, Vojtěch; Růžička, A.; Olejník, R.; Horáček, Michal

2015-01-01

Roč. 786, JUN 2015 (2015), s. 71-80 ISSN 0022-328X R&D Projects: GA ČR GAP106/10/0924 Institutional support: RVO:61388955 Keywords : Zirconium * Hafnium * Cyclopentadienyl Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.336, year: 2015

Hafnium Isotopic Variations in Central Atlantic Intraplate Volcanism

Science.gov (United States)

Geldmacher, J.; Hanan, B. B.; Hoernle, K.; Blichert-Toft, J.

2008-12-01

Although one of the geochemically best investigated volcanic regions on Earth, almost no Hf isotopic data have been published from the broad belt of intraplate seamounts and islands in the East Atlantic between 25° and 36° N. This study presents 176Hf/177Hf ratios from 61 representative samples from the Canary, Selvagen and Madeira Islands and nearby large seamounts, encompassing the full range of different evolutionary stages and geochemical endmembers. The majority of samples have mafic, mainly basaltic compositions with Mg-numbers within or near the range of magmas in equilibrium with mantle olivine (68-75). No correlation was found between Mg-number and 176Hf/177Hf ratios in the data set. In comparison to observed Nd isotope variations published for this volcanic province (6 ɛNd units), 176Hf/177Hf ratios span a larger range (14 ɛHf units). Samples from the Madeira archipelago have the most radiogenic compositions (176Hf/177Hfm= 0.283132-0.283335), widely overlapping the field for central Atlantic N-MORB. They form a relatively narrow, elongated trend (stretching over >6 ɛHf units) between a radiogenic MORB-like endmember and a composition located on the Nd-Hf mantle array. In contrast, all Canary Islands samples plot below the mantle array (176Hf/177Hfm = 0.282943-0.283067) and, despite being from an archipelago that stretches over a much larger geographic area, form a much denser cluster with less compositional variation (~4 ɛHf units). All samples from the seamounts NE of the Canaries, proposed to belong to the same Canary hotspot track (e.g. Geldmacher et al., 2001, JVGR 111; Geldmacher et al., 2005, EPSL 237), fall within the Hf isotopic range of this cluster. The cluster largely overlaps the composition of the proposed common mantle endmember 'C' (Hanan and Graham, 1996, Science 272) but spans a space between a more radiogenic (depleted) composition and a HIMU-type endmember. Although samples of Seine and Unicorn seamounts, attributed to the Madeira

Wake-up effects in Si-doped hafnium oxide ferroelectric thin films

International Nuclear Information System (INIS)

Zhou, Dayu; Xu, Jin; Li, Qing; Guan, Yan; Cao, Fei; Dong, Xianlin; Müller, Johannes; Schenk, Tony; Schröder, Uwe

2013-01-01

Hafnium oxide based ferroelectric thin films have shown potential as a promising alternative material for non-volatile memory applications. This work reports the switching stability of a Si-doped HfO 2 film under bipolar pulsed-field operation. High field cycling causes a “wake-up” in virgin “pinched” polarization hysteresis loops, demonstrated by an enhancement in remanent polarization and a shift of negative coercive voltage. The rate of wake-up is accelerated by either reducing the frequency or increasing the amplitude of the cycling field. We suggest de-pinning of domains due to reduction of the defect concentration at bottom electrode interface as origin of the wake-up

Extraction of hafnium with chelating agents from aqueous-alcoholic solutions

International Nuclear Information System (INIS)

Hala, J.; Prihoda, J.

1975-01-01

The extraction was studied of hafnium into solutions of N-benzoyl-N-phenylhydroxylamine, 2-thenoyltrifluoroacetone and di-n-butylphosphoric acid in benzene, toluene, chloroform and tetrachloromethane from aqueous alcoholic solutions with a formal acidity of 2M-HClO 4 . Methyl-, ethyl-, n- and isopropyl- and tert-butyl alcohol were used as organic components in the mixed aqueous-organic phase. In the extraction into N-benzoyl-N-phenylhydroxylamine the presence of the alcohols resulted in synergic effects analogous to the previously described extraction by substituted benzoylpyrazolone. With the other two extractants, the effect of the alcohols was antagonistic, due to the interaction of alcohol or water with the reagent in the organic phase, and to the decrease in the reagent distribution constant. (author)

Studies of high-K isomers in hafnium nuclei

International Nuclear Information System (INIS)

Sletten, G.; Gjoerup, N.L.

1991-01-01

K-isomeric states built on high-Ω Nilsson orbitals from deformation-aligned high-j levels near the Fermi surface are found to cluster in the neutron rich Hf, W and Os nuclei. It has been shown that some of the high seniority states of this type have decay properties that indicate strong mixing of configurations and that in Osmium nuclei γ-softness cause strong deviations from the well established K-selection rule. Also in the Hafnium nuclei is the expected forbiddenness in isomeric decays an order of magnitude smaller than expected from the K-selection rule. A new 9 quasiparticle isomer has been discovered in 175 Hf at I=57/2. This isomer has the anomalous decay as the dominant mode. Other lower seniority states are also identified. At spin 35/2 and 45/2 the deformation aligned states become yrast, but the structure of the yrast line to even higher spins is not yet understood. (author)

Luminescent determination of zirconium and hafnium with myricetin

International Nuclear Information System (INIS)

Talipov, Sh.T.; Zel'tser, L.E.; Morozova, L.A.; Tashkhodzhaev, A.T.

1978-01-01

Reaction of formation of 3, 5, 7, 3', 4', 5' - hexaoxiflavone - myricetin complexes with zirconium and hafnium ions has been the basis for development of luminescent method of determining these elements. Optimum conditions for complexing have been determined. For Hf they are : 8-9 HCl concentration, maximum fluorescence wave length (lambda fl.)of 520 nm, wave length of exciting light (lambda el) of 436 nm, for Zr lambda fl = 536nm, lambda el = 436 nm. Stable fluorescence establishes after 25 min. for Zr and after 15 min for Hf in the presence of 40% ethanol. Usage of various camouflage agents has permitted to attain high selectivity of the method. Possibility for determination of Zr with myricetin in the presence of a 10-time excess of Hf, Cr, Cu, 50-time excess of Mo and Ti is shown. Sensitivity of Zr determination is 2.0x10 μg -2 /ml, for Hf it is 9.0x10 μg -3 and mineral waters

Amorphous Hafnium-Indium-Zinc Oxide Semiconductor Thin Film Transistors

Directory of Open Access Journals (Sweden)

Sheng-Po Chang

2012-01-01

Full Text Available We reported on the performance and electrical properties of co-sputtering-processed amorphous hafnium-indium-zinc oxide (α-HfIZO thin film transistors (TFTs. Co-sputtering-processed α-HfIZO thin films have shown an amorphous phase in nature. We could modulate the In, Hf, and Zn components by changing the co-sputtering power. Additionally, the chemical composition of α-HfIZO had a significant effect on reliability, hysteresis, field-effect mobility (μFE, carrier concentration, and subthreshold swing (S of the device. Our results indicated that we could successfully and easily fabricate α-HfIZO TFTs with excellent performance by the co-sputtering process. Co-sputtering-processed α-HfIZO TFTs were fabricated with an on/off current ratio of ~106, higher mobility, and a subthreshold slope as steep as 0.55 V/dec.

21 CFR 177.2210 - Ethylene polymer, chloro-sulfonated.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene polymer, chloro-sulfonated. 177.2210... as Components of Articles Intended for Repeated Use § 177.2210 Ethylene polymer, chloro-sulfonated. Ethylene polymer, chlorosulfonated as identified in this section may be safely used as an article or...

21 CFR 177.1320 - Ethylene-ethyl acrylate copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-ethyl acrylate copolymers. 177.1320... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1320 Ethylene-ethyl acrylate copolymers. Ethylene-ethyl acrylate copolymers may be safely used to produce packaging materials, containers...

Intrinsic states and rotational bands in 177Pt

International Nuclear Information System (INIS)

Dracoulis, G.D.; Fabricius, B.; Bark, R.A.; Stuchbery, A.E.; Popescu, D.G.; Kibedi, T.

1989-11-01

The 149 Sm ( 32 S,4n) 177 Pt reaction has been used to populate excited states in the neutron-deficient nucleus 177 Pt. Rotational bands based on intrinsic states assigned to the 1/2-[521], 5/2-[521] and (mixed) 7/2+ [633] Nilsson configurations have been observed. In contrast to the neighbou-ring even isotope 176 Pt, anomalies attributed to shape co-existence at low spin have not been observed. Implications for the deformation of 177 Pt are discussed together with the systematics of intrinsic states in this region, and alignments and other properties of N=99 nuclei. 37 refs., 15 figs., 3 tabs

21 CFR 177.1310 - Ethylene-acrylic acid copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-acrylic acid copolymers. 177.1310 Section... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1310 Ethylene-acrylic acid copolymers. The ethylene-acrylic acid copolymers identified in paragraph (a) of this section may be safely...

21 CFR 177.1312 - Ethylene-carbon monoxide copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-carbon monoxide copolymers. 177.1312... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1312 Ethylene-carbon monoxide copolymers. The ethylene-carbon monoxide copolymers identified in paragraph (a) of this section may be safely...

21 CFR 177.1350 - Ethylene-vinyl acetate copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-vinyl acetate copolymers. 177.1350 Section... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1350 Ethylene-vinyl acetate copolymers. Ethylene-vinyl acetate copolymers may be safely used as articles or components of articles...

21 CFR 177.1950 - Vinyl chloride-ethylene copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vinyl chloride-ethylene copolymers. 177.1950... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1950 Vinyl chloride-ethylene copolymers. The vinyl chloride-ethylene copolymers identified in paragraph (a) of this section may be safely...

CD177 modulates human neutrophil migration through activation-mediated integrin and chemoreceptor regulation.

Science.gov (United States)

Bai, Ming; Grieshaber-Bouyer, Ricardo; Wang, Junxia; Schmider, Angela B; Wilson, Zachary S; Zeng, Liling; Halyabar, Olha; Godin, Matthew D; Nguyen, Hung N; Levescot, Anaïs; Cunin, Pierre; Lefort, Craig T; Soberman, Roy J; Nigrovic, Peter A

2017-11-09

CD177 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the antineutrophil cytoplasmic antibody antigen proteinase 3. CD177 associates with β2 integrins and recognizes platelet endothelial cell adhesion molecule 1 (PECAM-1), suggesting a role in neutrophil migration. However, CD177 pos neutrophils exhibit no clear migratory advantage in vivo, despite interruption of in vitro transendothelial migration by CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177 pos and CD177 neg neutrophils migrated comparably. CD177 ligation selectively impaired migration of CD177 pos neutrophils, an effect mediated through immobilization and cellular spreading on the transwell membrane. Correspondingly, CD177 ligation enhanced its interaction with β2 integrins, as revealed by fluorescence lifetime imaging microscopy, leading to integrin-mediated phosphorylation of Src and extracellular signal-regulated kinase (ERK). CD177-driven cell activation enhanced surface β2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. We conclude that CD177 signals in a β2 integrin-dependent manner to orchestrate a set of activation-mediated mechanisms that impair human neutrophil migration. © 2017 by The American Society of Hematology.

Production of {sup 177}Lu for targeted radionuclide therapy: Available options

Energy Technology Data Exchange (ETDEWEB)

Dah, Ashutosh [Isotope Production and Applications Division, Bhabha Atomic Research Centre (BARC), Mumbai (India); Pillai, Maroor Raghavan Ambikalmajan [Molecular Group of Companies. Kerala (India); Knapp, Furn F. Jr. [Medical Isotopes Program, Isotope Dept. Group, Oak Ridge National Laboratory (ORNL), Oak Ridge (United States)

2015-06-15

This review provides a comprehensive summary of the production of {sup 177}Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of {sup 177}Lu having the required quality for preparation of a variety of {sup 177}Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of {sup 177}Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. While both “direct” and “indirect” reactor production routes offer the possibility for sustainable {sup 177}Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. A broad understanding and discussion of the issues associated with {sup 177}Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of {sup 177}Lu-labeled radiopharmaceuticals, but also help future developments.

14 CFR 125.177 - Control of engine rotation.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Control of engine rotation. 125.177 Section... Requirements § 125.177 Control of engine rotation. (a) Except as provided in paragraph (b) of this section, each airplane must have a means of individually stopping and restarting the rotation of any engine in...

21 CFR 177.1830 - Styrene-methyl methacrylate copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Styrene-methyl methacrylate copolymers. 177.1830 Section 177.1830 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Us...

21 CFR 177.1820 - Styrene-maleic anhydride copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Styrene-maleic anhydride copolymers. 177.1820 Section 177.1820 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use...

21 CFR 177.2000 - Vinylidene chloride/methyl acrylate/methyl methacrylate polymers.

Science.gov (United States)

2010-04-01

... methacrylate polymers. 177.2000 Section 177.2000 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.2000 Vinylidene chloride/methyl acrylate/methyl methacrylate polymers. The vinylidene chloride/methyl acrylate...

Preparation of 177Lu-DTPA-BIS-BIOTIN and biodistribution evaluation in normal mice

International Nuclear Information System (INIS)

Deng Xinrong; Luo Zhifu; Du Jin

2010-01-01

The labeling method for 177 Lu-DTPA-BIS-BIOTIN was established, and the biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice was carried out as well. Under the optimal experimental condition (DTPA-BIS-BIOTIN 25 μg, pH=4.5 reacting at 80 degree C for 20 min), the labeling yield of 177 Lu-DTPA-BIS-BIOTIN is more than 99.0%. 177 Lu-DTPA-BIS-BIOTIN shows pretty good in vitro stability. The biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice shows a rapid blood clearance. The uptake of 177 Lu-DTPA-BIS-BIOTIN is mainly accumulated in liver, spleen and kidney. 177 Lu-DTPA-BIS-BIOTIN is excreted by kidney. The results provide the basis for further study on 177 Lu-DTPA-BIS-BIOTIN used in pretargeted radioimage and radiotherapy of cancer. (authors)

Differential perturbed angular correlation: use of physico-chemical study of some hafnium complexes derivates of hydroxy acids and EDTA

International Nuclear Information System (INIS)

Silveira, J.G. da.

1981-01-01

Measures of quadrupolar interaction to nucleus level of the metal, in some hafnium complexes are presented, including the analysis by combustion, microanalysis, infrared spectroscopy and thermogravimetry. The hyperfine interaction parameters, the temperature effects and the thermal neutrons capture effects over the irradiated Hf Y (Y = EDTA) are also studied. (author)

Rhodium and Hafnium Influence on the Microstructure, Phase Composition, and Oxidation Resistance of Aluminide Coatings

OpenAIRE

Maryana Zagula-Yavorska; Małgorzata Wierzbińska; Jan Sieniawski

2017-01-01

A 0.5 μm thick layer of rhodium was deposited on the CMSX 4 superalloy by the electroplating method. The rhodium-coated superalloy was hafnized and aluminized or only aluminized using the Chemical vapour deposition method. A comparison was made of the microstructure, phase composition, and oxidation resistance of three aluminide coatings: nonmodified (a), rhodium-modified (b), and rhodium- and hafnium-modified (c). All three coatings consisted of two layers: the additive layer and the interdi...

19 CFR 177.21 - Applicability.

Science.gov (United States)

2010-04-01

... (CONTINUED) ADMINISTRATIVE RULINGS Government Procurement; Country-of-Origin Determinations § 177.21... determinations relating to Government procurement under Title III, “Trade Agreements Act of 1979,” Pub. L. 96-39...

Study of bulk Hafnium oxide (HfO2) under compression

Science.gov (United States)

Pathak, Santanu; Mandal, Guruprasad; Das, Parnika

2018-04-01

Hafnium oxide (HfO2) is a technologically important material. This material has K-value of 25 and band gap 5.8 eV. A k value of 25-30 is preferred for a gate dielectric [1]. As it shows good insulating and capacitive properties, HfO2 is being considered as a replacement to SiO2 in microelectronic devices as gate dielectrics. On the other hand because of toughening mechanism due to phase transformation induced by stress field observed in these oxides, HFO2 has been a material of investigations in various configurations for a very long time. However the controversies about phase transition of HfO2 under pressure still exists. High quality synchrotron radiation has been used to study the structural phase transition of HfO2 under pressure.

Hafnium at subduction zones: isotopic budget of input and output fluxes; L'hafnium dans les zones de subduction: bilan isotopique des flux entrant et sortant

Energy Technology Data Exchange (ETDEWEB)

Marini, J.Ch

2004-05-15

Subduction zones are the primary regions of mass exchanges between continental crust and mantle of Earth through sediment subduction toward the earth's mantle and by supply of mantellic magmas to volcanic arcs. We analyze these mass exchanges using Hafnium and Neodymium isotopes. At the Izu-Mariana subduction zone, subducting sediments have Hf and Nd isotopes equivalent to Pacific seawater. Altered oceanic crust has Hf and Nd isotopic compositions equivalent to the isotopic budget of unaltered Pacific oceanic crust. At Luzon and Java subduction zones, arc lavas present Hf isotopic ratios highly radiogenic in comparison to their Nd isotopic ratios. Such compositions of the Luzon and Java arc lavas are controlled by a contamination of their sources by the subducted oceanic sediments. (author)

21 CFR 177.1040 - Acrylonitrile/styrene copoly-mer.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Acrylonitrile/styrene copoly-mer. 177.1040 Section 177.1040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food...

High spin K isomeric target of {sup 177m}Lu

Energy Technology Data Exchange (ETDEWEB)

Roig, O. E-mail: olivier.roig@cea.fr; Belier, G.; Daugas, J.-M.; Delbourgo, P.; Maunoury, L.; Meot, V.; Morichon, E.; Sauvestre, J.-E.; Aupiais, J.; Boulin, Y.; Fioni, G.; Letourneau, A.; Marie, F.; Ridikas, D

2004-03-21

The techniques used to produce a {sup 177m}Lu (J{sup {pi}}=23/2{sup -},T{sub 1/2}=160.4 days) target are described in this paper. Firstly, an isotopic separation of an enriched lutetium sample was used to reach a purity of {sup 176}Lu close to 99.993%. Afterwards, the high neutron flux of the Grenoble Institut Laue-Langevin reactor was used to produce the {sup 177m}Lu isomer by the {sup 176}Lu(n,{gamma}) reaction. Finally, a chemical separation was performed to extract 10{sup 13} nuclei of {sup 177m}Lu. Thanks to this experiment, we have been able to estimate the destruction cross-section of the {sup 177m}Lu.

40 CFR 265.177 - Special requirements for incompatible wastes.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Special requirements for incompatible wastes. 265.177 Section 265.177 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) INTERIM STATUS STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT...

Hafnium at subduction zones: isotopic budget of input and output fluxes

International Nuclear Information System (INIS)

Marini, J.Ch.

2004-05-01

Subduction zones are the primary regions of mass exchanges between continental crust and mantle of Earth through sediment subduction toward the earth's mantle and by supply of mantellic magmas to volcanic arcs. We analyze these mass exchanges using Hafnium and Neodymium isotopes. At the Izu-Mariana subduction zone, subducting sediments have Hf and Nd isotopes equivalent to Pacific seawater. Altered oceanic crust has Hf and Nd isotopic compositions equivalent to the isotopic budget of unaltered Pacific oceanic crust. At Luzon and Java subduction zones, arc lavas present Hf isotopic ratios highly radiogenic in comparison to their Nd isotopic ratios. Such compositions of the Luzon and Java arc lavas are controlled by a contamination of their sources by the subducted oceanic sediments. (author)

Labelling of the peptide Dota-Octreotate with Lutetium 177; Marcado del peptido Dota-Octreotate con Lutecio 177

Energy Technology Data Exchange (ETDEWEB)

Hernandez B, C.A

2004-07-01

In this work is described the optimization of the reaction conditions to obtain the complex {sup 177} Lu-Dota-TATE with a radiochemical purity > 95%, even so the studies of stability In vitro to the dilution in saline solution, stability in human serum and challenge to the cystein. The biodistribution studies are presented in mice Balb-C and the tests of biological recognition using one lines cellular of pancreatic adenoma (AR42-J). The obtained results show a high stability of the radio complex in vitro, since it doesn't suffer trans chelation from the Lutetium-177 to plasmatic proteins. The biodistribution tests in mice Balb-C demonstrated an appropriate lipophilly of the complex to be excreted in more proportion by the kidneys without significant accumulation in healthy tissues. It is necessary to mention that the drop activity specifies (3.54 {mu}g / 37 MBq) obtained in the irradiation of {sup 176} Lu{sub 2}O{sub 3} it allowed to verify the union of the {sup 177}Lu-Dota-Tate to membrane receivers but without being able to obtain the saturation curves and competition required to characterize quantitatively the biological recognition. (Author)

Thermal expansion studies on Hafnium titanate (HfTiO4)

International Nuclear Information System (INIS)

Panneerselvam, G.; Subramanian, G.G.S.; Antony, M.P.

2006-01-01

The lattice thermal expansion characteristics of hafnium titanate (HfTiO 4 ) have been studied by measuring the lattice parameter as a function of temperature by high temperature X-ray diffraction technique (HT-XRD) in the temperature range 298-1973K. Percentage linear thermal expansion and mean linear thermal expansion coefficients were computed from the lattice parameter data. The thermal expansion of HfTiO 4 is highly anisotropic. The expansivity along 'a' axis is large; as compared to the expansivity along 'b' axis which is negative below 1073 K. The percentage linear thermal expansion in the temperature range 298-1973 K along a, b and c axis are 2.74, 0.901 and 1.49 respectively. Thermal expansion values obtained in the present study are in reasonable agreement with the existing thermal expansion data. (author)

5 CFR 177.108 - Referral to Department of Justice.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Referral to Department of Justice. 177... ADMINISTRATIVE CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT § 177.108 Referral to Department of Justice. When Department of Justice approval or consultation is required, or the advice of the Department of Justice is...

21 CFR 177.1340 - Ethylene-methyl acrylate copolymer resins.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-methyl acrylate copolymer resins. 177.1340... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1340 Ethylene-methyl acrylate copolymer resins. Ethylene-methyl acrylate copolymer resins may be safely used as articles or components of...

19 CFR 177.1 - General ruling practice and definitions.

Science.gov (United States)

2010-04-01

... authority to represent is known, any person appearing before the Customs Service as an agent in connection... 19 Customs Duties 2 2010-04-01 2010-04-01 false General ruling practice and definitions. 177.1 Section 177.1 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY...

Production and evaluation of Lutetium-177 maltolate as a possible therapeutic agent

International Nuclear Information System (INIS)

Hakimi, A.; Jalilian, A. R.; Bahrami Samani, A.; Ghannadi Maragheh, M.

2012-01-01

Development of oral therapeutic radiopharmaceuticals is a new concept in radiopharmacy. Due to the interesting therapeutic properties of 177 Lu and oral bioavailability of maltolate (MAL) metal complexes, 177 Lu-maltolate ( 177 Lu-MAL) was developed as a possible therapeutic compound for ultimate oral administration. The specific activity of 2.6-3 GBq/mg was obtained by irradiation of natural Lu 2 O 3 sample with thermal neutron flux of 4x10 13 n.cm -2 .s -1 for Lu-177. The product was converted into chloride form which was further used for labeling maltol (MAL). At optimized conditions a radiochemical purity of about >99% was obtained for 177 Lu-MAL shown by ITLC (specific activity, 970-1000 Mbq/mmole). The stability of the labeled compound as well as the partition coefficient was determined in the final solution up to 24h. Biodistribution studies of Lu-177 chloride and 177 Lu-MAL were carried out in wild-type rats for post-oral distribution phase data. Lu-MAL is a possible therapeutic agent in human malignancies for the bone palliation therapy so the efficacy of the compound should be tested in various animal models.

Thermal neutron capture cross section for the K isomer 177Lum

International Nuclear Information System (INIS)

Belier, G.; Roig, O.; Daugas, J.-M.; Giarmana, O.; Meot, V.; Letourneau, A.; Marie, F.; Foucher, Y.; Aupiais, J.; Abt, D.; Jutier, Ch.; Le Petit, G.; Bettoni, C.; Gaudry, A.; Veyssiere, Ch.; Barat, E.; Dautremer, T.; Trama, J.-Ch.

2006-01-01

The thermal neutron radiative capture cross section for the K isomeric state in 177 Lu has been measured for the first time. Several 177 Lu m targets have been prepared and irradiated in various neutron fluxes at the Lauee Langevin Institute in Grenoble and at the CEA reactors OSIRIS and ORPHEE in Saclay. The method consists of measuring the 178 Lu activity by γ-ray spectroscopy. The values obtained in four different neutron spectra have been used to calculate the resonance integral of the radiative capture cross section for 177 Lu m . In addition, an indirect method leads to the determination of the 177 Lu g neutron radiative capture cross section

21 CFR 177.2410 - Phenolic resins in molded articles.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Phenolic resins in molded articles. 177.2410... as Components of Articles Intended for Repeated Use § 177.2410 Phenolic resins in molded articles. Phenolic resins identified in this section may be safely used as the food-contact surface of molded...

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

Science.gov (United States)

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

2015-01-01

Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 ((90)Y) and lutetium-177 ((177)Lu)-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. 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) (177)Lu was used with GMP-certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC-SG and HPLC methods. A total of 17 [(177)Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [(177)Lu]-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. The automated synthesis of [(177)Lu]-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 (177)Lu and almost negligible radiation exposure of the operators.

Surface State Capture Cross-Section at the Interface between Silicon and Hafnium Oxide

Directory of Open Access Journals (Sweden)

Fu-Chien Chiu

2013-01-01

Full Text Available The interfacial properties between silicon and hafnium oxide (HfO2 are explored by the gated-diode method and the subthreshold measurement. The density of interface-trapped charges, the current induced by surface defect centers, the surface recombination velocity, and the surface state capture cross-section are obtained in this work. Among the interfacial properties, the surface state capture cross-section is approximately constant even if the postdeposition annealing condition is changed. This effective capture cross-section of surface states is about 2.4 × 10−15 cm2, which may be an inherent nature in the HfO2/Si interface.

A thermally robust and thickness independent ferroelectric phase in laminated hafnium zirconium oxide

Directory of Open Access Journals (Sweden)

S. Riedel

2016-09-01

Full Text Available Ferroelectric properties in hafnium oxide based thin films have recovered the scaling potential for ferroelectric memories due to their ultra-thin-film- and CMOS-compatibility. However, the variety of physical phenomena connected to ferroelectricity allows a wider range of applications for these materials than ferroelectric memory. Especially mixed HfxZr1-xO2 thin films exhibit a broad compositional range of ferroelectric phase stability and provide the possibility to tailor material properties for multiple applications. Here it is shown that the limited thermal stability and thick-film capability of HfxZr1-xO2 can be overcome by a laminated approach using alumina interlayers.

Differential expression of granulopoiesis related genes in neutrophil subsets distinguished by membrane expression of CD177

DEFF Research Database (Denmark)

Hu, Nan; Mora-Jensen, Helena; Theilgaard-Mønch, Kim

2014-01-01

OBJECTIVE: Differential gene expression in CD177+ and CD177- neutrophils was investigated, in order to detect possible differences in neutrophil function which could be related to the pathogenesis of ANCA-associated Vasculitides (AAV). METHODS: Neutrophils were isolated from healthy controls (HC......) with high, negative or bimodal CD177 expression, and sorted into CD177+ and CD177- subpopulations. Total RNA was screened for expression of 24,000 probes with Illumina Ref-8 Beadchips. Genes showing differential expression between CD177+ and CD177- subsets in microarray analysis were re-assessed using...... quantitative-PCR. CD177 expression on neutrophil precursors in bone marrow was analyzed using quantitative PCR and flowcytometry. RESULTS: The proportion of CD177+ cells increased during neutrophil maturation in bone marrow. Fold change analysis of gene expression profile of sorted CD177+ and CD177...

21 CFR 177.2710 - Styrene-divinylbenzene resins, cross-linked.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Styrene-divinylbenzene resins, cross-linked. 177.2710 Section 177.2710 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use Only as Components of Articles Intended...

19 CFR 177.25 - Form and content of request.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Form and content of request. 177.25 Section 177.25....25 Form and content of request. (a) A request for an advisory ruling shall be in writing and shall... for which a country-of-origin determination is requested; (3) The country or instrumentality an...

Synthesis of DOTMP and biodistribution and imaging study of 177-Lu-DOTMP

International Nuclear Information System (INIS)

Deng Xinrong; Luo Zhifu; Xiang Xueqin; Li Fenglin; Fan Caiyun; Liu Zihua; Ye Zhaoyun; Li Hongyu; Chen Yang; Zhuang Ling

2012-01-01

Cyclen (1, 4, 7, 10-tetraazacyclododecane) and H 3 PO 3 was used to synthesis DOTMP (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-Tetraamino methylenephosphonate). 177 Lu was produced by irradiating enriched lutetium oxide ( 176 Lu 2 O 3 ) with thermal neutron flux of 2' × 10 13 n/cm 2 /S in swimming pool reactor (SPR) for 10 days. And then DOTMP was labelled by 177 Lu. The biodistribution of 177 Lu-DOTMP in model mice bearing S180 sarcoma and SPECT imaging in Japanese white rabbit were also carried out. The results showed that the total activity of 177 LuCl 3 solution obtained was 9.19 × 10 5 MBq after corresponding chemical process. According to the optimal condition of the labeling experiment, the labelling efficiency of 177 Lu-DOTMP was 99.4%. The results of biodistribution study indicated that 177 Lu-DOTMP eliminated rapidly from blood and was delivered to target bone. The radioactivity uptake was mainly in bone and less in other viscera. The results of SPECT imaging showed that the radioactivity was accumulated in bladder. 177 Lu-DOTMP was mainly excreted by kidney. The uptake of the activity in the skeleton was observed within 22 h postinjection and it became quite significant at 46 h post injection. It indicated that 177 Lu-DOTMP has good bone targeting and is worthy of further research. (authors)

Influence of plastic deformation on nitriding of a molybdenum-hafnium alloy

International Nuclear Information System (INIS)

Lakhtin, Yu.M.; Kogan, Ya.D.; Shashkov, D.P.; Likhacheva, T.E.

1982-01-01

The influence of a preliminary plastic strain on the structure and properties of molybdenum alloy with 0.2 wt.% Hf upon nitriding in the ammonia medium at 900-1200 deg C during 1-6 h is investigated. The study of microhardness distribution across the nitrided layer thickness has shown that with increase of the degree of preliminary plastic strain up to 50 % the nitrided layer hardness decreases and with further reduction growth up to 90 % - increases. Nitriding sharply (hundred times) increases wear resistance of molybdenum alloy with hafnium addition. At the reduction degree 25 % the wear resistance is less than at other values of percentage reduction in area owing to the minimum thickness of the nitride zone. The alloy strained before nitriding by 25 % has shown the best results during heat resistance testing

Gamma radiation exposure of accompanying persons due to Lu-177 patients

Directory of Open Access Journals (Sweden)

Kovan Bilal

2015-01-01

Full Text Available Neuroendocrine tumours (NET are cancers usually observed and arisen in the stomach, intestine, pancreas and breathing system. Recently, radionuclide therapy applications with Lu-177 peptide compound are rapidly growing; especially effective clinical results are obtained in the treatment of well-differentiated and metastatic NET. In this treatment, Lu-177-DOTA, a beta emitter radioisotope in the radiopharmaceutical form, is given to the patient by intravenous way. Lu-177 has also gamma rays apart from beta rays. Gamma rays have 175 keV average energy and these gamma rays should be under the control in terms of radiation protection. In this study, we measured the exposure dose from the Lu-177 patient.

Dielectric response and ac conductivity analysis of hafnium oxide nanopowder

International Nuclear Information System (INIS)

Karahaliou, P K; Xanthopoulos, N; Krontiras, C A; Georga, S N

2012-01-01

The dielectric response of hafnium oxide nanopowder was studied in the frequency range of 10 -2 -10 6 MHz and in the temperature range of 20-180 °C. Broadband dielectric spectroscopy was applied and the experimental results were analyzed and discussed using the electric modulus (M*) and alternating current (ac) conductivity formalisms. The analyses of the dc conductivity and electric modulus data revealed the presence of mechanisms which are thermally activated, both with almost the same activation energy of 1.01 eV. A fitting procedure involving the superposition of the thermally activated dc conductivity, the universal dielectric responce and the near constant loss terms has been used to describe the frequency evolution of the real part of the specific electrical conductivity. The conductivity master curve was obtained, suggesting that the time-temperature superposition principle applies for the studied system, thus implying that the conductivity mechanisms are temperature independent.

Interface and oxide traps in high-κ hafnium oxide films

International Nuclear Information System (INIS)

Wong, H.; Zhan, N.; Ng, K.L.; Poon, M.C.; Kok, C.W.

2004-01-01

The origins of the interface trap generation and the effects of thermal annealing on the interface and bulk trap distributions are studied in detail. We found that oxidation of the HfO 2 /Si interface, removal of deep trap centers, and crystallization of the as-deposited film will take place during the post-deposition annealing (PDA). These processes will result in the removal of interface traps and deep oxide traps and introduce a large amount of shallow oxide traps at the grain boundaries of the polycrystalline film. Thus, trade-off has to be made in considering the interface trap density and oxide trap density when conducting PDA. In addition, the high interface trap and oxide trap densities of the HfO 2 films suggest that we may have to use the SiO 2 /HfO 2 stack or hafnium silicate structure for better device performance

Effects of oxygen partial pressure and annealing temperature on the residual stress of hafnium oxide thin-films on silicon using synchrotron-based grazing incidence X-ray diffraction

Energy Technology Data Exchange (ETDEWEB)

Biswas, Debaleen [Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India); Sinha, Anil Kumar [ISU, Raja Ramanna Centre for Advanced Technology, Indore 452 013 (India); Homi Bhabha National Institute, BARC, Mumbai 400 094 (India); Chakraborty, Supratic, E-mail: supratic.chakraborty@saha.ac.in [Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India)

2016-10-30

Highlights: • Residual stress estimation thin hafnium oxide film with thickness of <10 nm. • A mathematical expression is proposed for stress estimation of thin-film using GIXRD. • Residual stress varies with argon content in Ar/O{sub 2} plasma and annealing temperature. • Variation of stress is explained by IL swelling and enhanced structural relaxation. - Abstract: Synchrotron radiation-based grazing incidence X-ray diffraction (GI-XRD) technique is employed here to estimate the residual stress of < 10 nm thin hafnium oxide film deposited on Si (100) substrate at different argon/oxygen ratios using reactive rf sputtering. A decrease in residual stress, tensile in nature, is observed at higher annealing temperature for the samples deposited with increasing argon ratio in the Ar/O{sub 2} plasma. The residual stress of the films deposited at higher p{sub Ar} (Ar:O{sub 2} = 4:1) is also found to be decreased with increasing annealing temperature. But the stress is more or less constant with annealing temperature for the films deposited at lower Ar/O{sub 2} (1:4) ratio. All the above phenomena can be explained on the basis of swelling of the interfacial layer and enhanced structural relaxation in the presence of excess Hf in hafnium oxide film during deposition.

Symbiotic nature of the object M1-77

International Nuclear Information System (INIS)

Kondrt'eva, L.N.

2004-01-01

Many year spectral observations show, that the object M1-77 is the symbiotic system, which consists of a M-giant and a B-star. An emission spectra arises from an envelope, which was formed from a giant's extended atmosphere, and now is ionized by the hotter component. Some spectral changes were registered in M1-77: the forbidden lines intensities increase relatively to that of Hα. It is connected with the decrease of hydrogen emission. (author)

Peptide receptor radionuclide therapy (PRRT) using Lu-177 DOTA-NOC and Lu-177 DOTA-TATE: Comparative results

International Nuclear Information System (INIS)

Wehrmann, C.; Senftleben, S.; Baum, R.P.

2007-01-01

Full text: Aim: One of the few treatment options for inoperable neuroendocrine tumors (NET) is peptide receptor radiotherapy with somatostatin analogues. DOTA-NOC shows the highest affinity to the somatostatin receptors (sstr) 3 and 5 and a very high affinity to sstr 2. We compared the dosimetric parameters uptake, half-life (kinetics) and mean absorbed organ and tumor doses of 177 Lu DOTANOC and 177 Lu DOTA-TATE. Methods: 139 patients with neuroendocrine tumors with high sstr expression (verified by Ga-68 DOTA-NOC PET/CT) were studied. 130 patients (57m, 73f; aged 60±11a) were treated with 2.5-7.4 GBq Lu-177 DOTA-TATE and 9 patients (3m, 6f, aged 64±10a) with 3.6-7.4 GBq Lu-177 DOTA-NOC. Whole-body scans were performed after 0.5h, 3h, 24h, 48h, 72h and 96h p.i. Blood samples from 23 patients were obtained after therapy. By means of geometric mean and after background correction, ROI results were used to calculate the estimated absorbed organ and tumor doses according to the MIRD-scheme (OLINDA software). Results: Lu-177 DOTA-NOC showed a higher uptake as compared to Lu-177 DOTATATE (=100%): for whole-body about 38% and in normal tissue 36%, in the spleen 17% and in the kidneys 18%. The tumor uptake was about 5% higher for DOTA-TATE. The effective half-life for whole-body was comparable for both peptides (t1/2a NOC 2.9h vs. TATE 2.4h and t1/2b NOC 54h vs. TATE 56h). In normal tissue, t1/2a was similar (NOC 3.3h; TATE 2.6h) but the t1/2b was longer for DOTA-TATE (NOC 43h; TATE 48h). t1/2b was longer for DOTA-NOC in the spleen (NOC 81h; TATE 72h) and in the kidney (NOC 68.1h; TATE 65h). The mean absorbed dose in the kidney (TATE 5Sv; NOC 6Sv) and spleen (TATE 7Sv; NOC 8Sv) was higher for DOTA-NOC. In the tumor, the t1/2b was higher for DOTA-TATE (NOC 65h; TATE 77h). For DOTA-TATE the whole-body dose was lower (0.27Sv) as compared to DOTA-NOC (0.38 Sv) (significant by unpaired sign test). The estimated mean absorbed tumor doses were 47+/-66 Sv for DOTA-TATE and 35

12 CFR 225.177 - Definitions.

Science.gov (United States)

2010-01-01

... pursuant to this subpart, including through a private equity fund that the financial holding company... in the determination of major policies of the company and whose decisions are limited by policy... COMPANIES AND CHANGE IN BANK CONTROL (REGULATION Y) Regulations Merchant Banking Investments § 225.177...

Pyroelectricity of silicon-doped hafnium oxide thin films

Science.gov (United States)

Jachalke, Sven; Schenk, Tony; Park, Min Hyuk; Schroeder, Uwe; Mikolajick, Thomas; Stöcker, Hartmut; Mehner, Erik; Meyer, Dirk C.

2018-04-01

Ferroelectricity in hafnium oxide thin films is known to be induced by various doping elements and in solid-solution with zirconia. While a wealth of studies is focused on their basic ferroelectric properties and memory applications, thorough studies of the related pyroelectric properties and their application potential are only rarely found. This work investigates the impact of Si doping on the phase composition and ferro- as well as pyroelectric properties of thin film capacitors. Dynamic hysteresis measurements and the field-free Sharp-Garn method were used to correlate the reported orthorhombic phase fractions with the remanent polarization and pyroelectric coefficient. Maximum values of 8.21 µC cm-2 and -46.2 µC K-1 m-2 for remanent polarization and pyroelectric coefficient were found for a Si content of 2.0 at%, respectively. Moreover, temperature-dependent measurements reveal nearly constant values for the pyroelectric coefficient and remanent polarization over the temperature range of 0 ° C to 170 ° C , which make the material a promising candidate for IR sensor and energy conversion applications beyond the commonly discussed use in memory applications.

Implantation of titanium, chromium, yttrium, molybdenum, silver, hafnium, tantalum, tungsten and platinum ions generated by a metal vapor vacuum ion source into 440C stainless steel

International Nuclear Information System (INIS)

Sasaki, Jun; Hayashi, Kazunori; Sugiyama, Kenji; Ichiko, Osami; Hashiguchi, Yoshihiro

1992-01-01

Titanium, yttrium, molybdenum, silver, chromium, hafnium, tantalum, tungsten and platinum ions generated by a metal vapor vacuum arc (MEVVA) ion source were implanted into 440C stainless steel in the dose region 10 17 ions cm -2 with extraction voltages of up to 70 kV. Glow discharge spectroscopy (GDS), friction coefficient, and Vickers microhardness of the specimens were studied. Grooves made by friction tests were investigated by electron probe microanalysis (EPMA). GDS showed incorporation of carbon in the yttrium, hafnium, tantalum, tungsten and platinum implanted specimens, as well as titanium implanted samples. A large amount of oxygen was observed in the yttrium implanted specimen. The friction coefficient was measured by reciprocating sliding of an unimplanted 440C ball without lubricant at a load of 0.245 N. The friction decreased and achieved a stable state after implantation of titanium, hafnium and tantalum. The friction coefficient of the platinum implanted specimen showed a gradual decrease after several cycles of sliding at high friction coefficient. The yttrium implanted sample exhibited a decreased but slightly unstable friction coefficient. Results from EPMA showed that the implanted elements, which gave decreased friction, remained even after sliding of 200 cycles. Implantation of chromium, molybdenum, silver and tungsten did not provide a decrease in friction and the implants were gone from the wear grooves after the sliding tests. (orig.)

Critical evaluation of the determination of zirconium and hafnium by instrumental and radiochemical neutron activation analysis

International Nuclear Information System (INIS)

Burger, Mario; Kraehenbuehl, Urs

1991-01-01

Neutron activation analysis (instrument or radiochemical) is suitable for the determination of zirconium and hafnium in samples of geochemical origin only when sufficient attention is paid to inter-fering nuclides. The size of the necessary correction for INAA depends on the composition of the sample; this problem is discussed. The radio-chemical technique which is recommended involves separation of the samples, precipitations and anion-exchange separation. Results are given for various standard reference materials and for meteorites. (author). 12 refs.; 1 fig.; 9 tabs

Evidence for inelastic neutron acceleration by the 177Lu isomer

International Nuclear Information System (INIS)

Roig, O.; Belier, G.; Meot, V.; Daugas, J.-M.; Abt, D.; Aupiais, J.; Jutier, Ch.; Petit, G. Le; Letourneau, A.; Marie, F.; Veyssiere, Ch.

2006-01-01

The neutron burnup cross section σ burnup m on the long-lived metastable state of 177 Lu has been measured from a specially designed isomeric target. The Maxwellian averaged cross section obtained for this reaction on 177 Lu m (J π =23/2 - ) is σ burnup m =626±45 b at the reactor temperature T=323 K. The difference between the burnup cross section and the previously measured capture cross section σ n,γ clearly shows a possible existence of 177 Lu m deexcitation via (n,n ' ) inelastic neutron acceleration channels. The results are interpreted in terms of a statistical approach using parameters from a deformed optical potential calculation

A fast response hafnium selective polymeric membrane electrode based on N,N'-bis(α-methyl-salicylidene)-dipropylenetriamine as a neutral carrier

International Nuclear Information System (INIS)

Rezaei, B.; Meghdadi, S.; Zarandi, R. Fazel

2008-01-01

In this study a new hafnium selective sensor was fabricated from polyvinylchloride (PVC) matrix membrane containing neutral carrier N,N'-bis(α-methyl-salicylidene)-dipropylenetriamine (Mesaldpt) as a new ionophore, sodium tetraphenyl borate (NaTPB) as anionic discriminator and dioctyl phthalate (DOP) as plasticizing solvent mediator in tetrahydrofuran solvent. The electrode exhibits Nernstian response for Hf 4+ (Hafnium(IV)) over a wide concentration range (2.0 x 10 -7 to 1.0 x 10 -1 M) with the determination coefficient of 0.9966 and slope of 15.1 ± 0.1 mV decades -1 . The limit of detection is 1.9 x 10 -7 M. The electrode has a fast response time of 18 s and a working pH range of 4-8. The proposed membrane shows excellent discriminating ability towards Hf 4+ ion with regard to several alkali, alkaline earth transition and heavy metal ions. It can be used over a period of 1.5 months with good reproducibility. It is successfully applied for direct determination of Hf 4+ in solutions by standard addition method for real sample analysis

46 CFR 177.310 - Satisfactory service as a design basis.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Satisfactory service as a design basis. 177.310 Section... (UNDER 100 GROSS TONS) CONSTRUCTION AND ARRANGEMENT Hull Structure § 177.310 Satisfactory service as a design basis. When scantlings for the hull, deckhouse, and frames of the vessel differ from those...

Study of hafnium (IV) oxide nanoparticles synthesized by polymerized complex and polymer precursor derived sol-gel methods

KAUST Repository

Ramos-Gonzá lez, R.; Garcí a-Cerda, L. A.; Alshareef, Husam N.; Gnade, Bruce E.; Quevedo-Ló pez, Manuel Angel Quevedo

2010-01-01

This work reports the preparation and characterization of hafnium (IV) oxide (HfO2) nanoparticles grown by derived sol-gel routes that involves the formation of an organic polymeric network. A comparison between polymerized complex (PC) and polymer precursor (PP) methods is presented. For the PC method, citric acid (CA) and ethylene glycol (EG) are used as the chelating and polymerizable reagents, respectively. In the case of PP method, poly(acrylic acid) (PAA) is used as the chelating reagent. In both cases, different precursor gels were prepared and the hafnium (IV) chloride (HfCl4) molar ratio was varied from 0.1 to 1.0 for the PC method and from 0.05 to 0.5 for the PP method. In order to obtain the nanoparticles, the precursors were heat treated at 500 and 800 °C. The thermal characterization of the precursor gels was carried out by thermogravimetric analysis (TGA) and the structural and morphological characterization by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The XRD patterns of the samples obtained by both methods shows the formation of HfO2 at 500 °C with monoclinic crystalline phase. The PC method exhibited also the cubic phase. Finally, the HfO2 nanoparticles size (4 to 11 nm) was determined by TEM and XRD patterns. © (2010) Trans Tech Publications.

Study of hafnium (IV) oxide nanoparticles synthesized by polymerized complex and polymer precursor derived sol-gel methods

KAUST Repository

Ramos-González, R.

2010-03-01

This work reports the preparation and characterization of hafnium (IV) oxide (HfO2) nanoparticles grown by derived sol-gel routes that involves the formation of an organic polymeric network. A comparison between polymerized complex (PC) and polymer precursor (PP) methods is presented. For the PC method, citric acid (CA) and ethylene glycol (EG) are used as the chelating and polymerizable reagents, respectively. In the case of PP method, poly(acrylic acid) (PAA) is used as the chelating reagent. In both cases, different precursor gels were prepared and the hafnium (IV) chloride (HfCl4) molar ratio was varied from 0.1 to 1.0 for the PC method and from 0.05 to 0.5 for the PP method. In order to obtain the nanoparticles, the precursors were heat treated at 500 and 800 °C. The thermal characterization of the precursor gels was carried out by thermogravimetric analysis (TGA) and the structural and morphological characterization by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The XRD patterns of the samples obtained by both methods shows the formation of HfO2 at 500 °C with monoclinic crystalline phase. The PC method exhibited also the cubic phase. Finally, the HfO2 nanoparticles size (4 to 11 nm) was determined by TEM and XRD patterns. © (2010) Trans Tech Publications.

Targeting angiogenesis for radioimmunotherapy with a {sup 177}Lu-labeled antibody

Energy Technology Data Exchange (ETDEWEB)

Ehlerding, Emily B.; Hernandez, Reinier [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Lacognata, Saige; Jiang, Dawei [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Ferreira, Carolina A. [University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); Goel, Shreya [University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States); Jeffery, Justin J. [University of Wisconsin - Madison, Small Animal Imaging Facility, Madison, WI (United States); Theuer, Charles P. [TRACON Pharmaceuticals, Inc., San Diego, CA (United States); Cai, Weibo [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States)

2018-01-15

Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with {sup 177}Lu (t{sub 1/2} 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: {sup 177}Lu only, TRC105 only, {sup 177}Lu-DTPA-IgG (a nonspecific antibody), {sup 177}Lu-DTPA-TRC105 low-dose, and {sup 177}Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of {sup 177}Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose {sup 177}Lu-DTPA-TRC105. Biodistribution studies indicated steady uptake of {sup 177}Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival (p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses. {sup 177}Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a

21 CFR 177.1900 - Urea-formaldehyde resins in molded articles.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Urea-formaldehyde resins in molded articles. 177... for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1900 Urea-formaldehyde resins in molded articles. Urea-formaldehyde resins may be safely used as the food-contact surface...

Rapid formation of nanocrystalline HfO2 powders from amorphous hafnium hydroxide under ultrasonically assisted hydrothermal treatment

International Nuclear Information System (INIS)

Meskin, Pavel E.; Sharikov, Felix Yu.; Ivanov, Vladimir K.; Churagulov, Bulat R.; Tretyakov, Yury D.

2007-01-01

Peculiarities of hafnium hydroxide hydrothermal decomposition were studied by in situ heat flux calorimetry for the first time. It was shown that this process occurs in one exothermal stage (ΔH = -17.95 kJ mol -1 ) at 180-250 deg. C resulting in complete crystallization of amorphous phase with formation of pure monoclinic HfO 2 . It was found that the rate of m-HfO 2 formation can be significantly increased by combining hydrothermal treatment with simultaneous ultrasonic activation

Improvement of aging kinetics and precipitate size refinement in Mg–Sn alloys by hafnium additions

Energy Technology Data Exchange (ETDEWEB)

Behdad, S. [Department of Mechanical and Materials Engineering, Florida International University, Miami, FL 33174 (United States); Zhou, L. [Department of Materials Science and Engineering and Advanced Materials Processing and Analysis Center, University of Central Florida, Orlando, FL 32816 (United States); Henderson, H.B.; Manuel, M.V. [Department of Materials Science and Engineering, University of Florida, Gainesville, FL 32611 (United States); Sohn, Y. [Department of Materials Science and Engineering and Advanced Materials Processing and Analysis Center, University of Central Florida, Orlando, FL 32816 (United States); Agarwal, A. [Department of Mechanical and Materials Engineering, Florida International University, Miami, FL 33174 (United States); Boesl, B., E-mail: bboesl@fiu.edu [Department of Mechanical and Materials Engineering, Florida International University, Miami, FL 33174 (United States)

2016-01-10

Two Mg–Sn alloys were microalloyed by addition of Hafnium and their age-hardening response was studied at 200 °C. Time to reach peak hardness was significantly reduced and improved by Hf addition. TEM study showed Hf clusters in the close vicinity and at the surface of Mg{sub 2}Sn precipitates, which confirms that Hf clusters act as additional nucleation centers for Mg{sub 2}Sn precipitate formation. Our results support the validity of thermokinetic criterion proposed by Mendis for selection of microalloying elements in order to refine precipitate size, accelerate aging kinetics and enhance peak hardness.

19 CFR 177.26 - Where request filed.

Science.gov (United States)

2010-04-01

... (CONTINUED) ADMINISTRATIVE RULINGS Government Procurement; Country-of-Origin Determinations § 177.26 Where... International Trade, Headquarters, U.S. Customs and Border Protection, 1300 Pennsylvania Avenue, NW., Washington...

47 CFR 17.7 - Antenna structures requiring notification to the FAA.

Science.gov (United States)

2010-10-01

... the FAA. 17.7 Section 17.7 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL CONSTRUCTION... Antenna structures requiring notification to the FAA. A notification to the Federal Aviation... area of each heliport specified in paragraph (d) of this section. (c) When requested by the FAA, any...

Preparation of 177Lu-DOTA/DTPA-Bz-Cys-RGD dimer and biodistribution evaluation in normal mice

International Nuclear Information System (INIS)

Sheng Feng; Jia Bing; Wang Fan; He Weiwei; Liu Zhaofei; Zhao Huiyun

2008-01-01

177 Lu-DOTA-Bz-Cys-RGD dimer and 177 Lu-DTPA-Bz-Cys-RGD dimer were prepared, and the in vitro and in vivo properties were compared. TLC and HPLC show that the labeling yields of two radiolabeled compounds are more than 95% under optimal conditions (pH=5.0, reacting at 100 degree C for 15-20 min), and the two radiolabeled compounds show pretty good in vitro stability. HPLC analyses and lg P values reveal that lipophilicity of 177 Lu-DOTA-Bz-Cys- RGD dimer is higher than 177 Lu-DTPA-Bz-Cys-RGD dimer. The uptake of 177 Lu-DTPA-Bz-Cys- RGD dimer in other tissues is significantly higher than that of 177 Lu-DOTA-Bz-Cys-RGD dimer at 4 h postinjection, except for blood and spleen. The in vivo stability of 177 Lu-DOTA-Bz-Cys-RGD dimer is much better than 177 Lu-DTPA-Bz-Cys-RGD dimer. Bz-DOTA is an ideal bifunctional chelator for 177 Lu labeling of RGD dimer. (authors)

Engineering Assessment and Certification of Integrity of the 177-R2 tank system

International Nuclear Information System (INIS)

Graser, D.A.; Schwartz, W.W.

1993-10-01

This Engineering Assessment and Certification of Integrity of retention tanks 177-R2U1, 177-R2Al, and 177-R2A2 has been prepared in response to 40 CFR 265.192(a) and 22 CCR 66265.192(a) for new tank systems that store hazardous waste and have secondary containment. The regulations require that this assessment be completed and certified by an independent, qualified, California-registered professional engineer before the tank system is placed in use as a hazardous waste storage tank system. The technical assessments for the 177-R2Ul, 177-R2A1, and 177-R2A2 tank systems have been reviewed by an independent, qualified, California-registered professional engineer, who has certified that the tank systems have sufficient structural integrity, are acceptable for transferring and storing hazardous waste, are compatible with the stored waste, and the tanks and containment system are suitably designed to achieve the requirements of the applicable regulations so they will not collapse, rupture, or fail. This document will be kept on file by the Lawrence Livermore National Laboratory (LLNL) Environment Protection Department

Solvent extraction of hafnium(IV) by dinonylnaphthalene sulfonic acid from mixed aqueous-organic media

International Nuclear Information System (INIS)

Hala, J.; Piperkovova, H.

1979-01-01

The extraction of hafnium(IV) by heptane and toluene solutions of dinonylnaphthalene sulfonic acid (HD) from mixed aqueous-organic solutions has been studied. Alcohols, ketones, carboxylic acids, cyclic ethers, dimethylsulfoxide and dimethylformamide were used as the organic component of the mixed phase. Methanol, ethanol, formic acid and dioxane increased the extractability of Hf(IV) whereas other solvents showed only an antagonistic effect. The results were discussed from the point of view of the changes in micellar structure of HD, and compared with the uptake of Hf(IV) by resinous cation exchangers. The solubilization by HD of alcohols, carboxylic acids and dimethylsulfoxide was demonstrated by using the corresponding 14 C and 35 S labelled compounds. (author)

The interfacial orientation relationship of oxide nanoparticles in a hafnium-containing oxide dispersion-strengthened austenitic stainless steel

Energy Technology Data Exchange (ETDEWEB)

Miao, Yinbin, E-mail: miao2@illinois.edu [Department of Nuclear, Plasma and Radiological Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Mo, Kun [Nuclear Engineering Division, Argonne National Laboratory, Lemont, IL 60493 (United States); Cui, Bai [Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588 (United States); Department of Material Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Chen, Wei-Ying [Department of Nuclear, Plasma and Radiological Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Miller, Michael K.; Powers, Kathy A. [Center for Nanophase Materials Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37830 (United States); McCreary, Virginia; Gross, David [Department of Material Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Almer, Jonathan [X-ray Science Division, Argonne National Laboratory, Lemont, IL 60493 (United States); Robertson, Ian M. [Department of Material Science and Engineering, University of Wisconsin-Madison, Madison, WA 53706 (United States); Department of Material Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Stubbins, James F. [Department of Nuclear, Plasma and Radiological Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States)

2015-03-15

This work reports comprehensive investigations on the orientation relationship of the oxide nanoparticles in a hafnium-containing austenitic oxide dispersion-strengthened 316 stainless steel. The phases of the oxide nanoparticles were determined by a combination of scanning transmission electron microscopy–electron dispersive X-ray spectroscopy, atom probe tomography and synchrotron X-ray diffraction to be complex Y–Ti–Hf–O compounds with similar crystal structures, including bixbyite Y{sub 2}O{sub 3}, fluorite Y{sub 2}O{sub 3}–HfO{sub 2} solid solution and pyrochlore (or fluorite) Y{sub 2}(Ti,Hf){sub 2−x}O{sub 7−x}. High resolution transmission electron microscopy was used to characterize the particle–matrix interfaces. Two different coherency relationships along with one axis-parallel relation between the oxide nanoparticles and the steel matrix were found. The size of the nanoparticles significantly influences the orientation relationship. The results provide insight into the relationship of these nanoparticles with the matrix, which has implications for interpreting material properties as well as responses to radiation. - Highlights: • The oxide nanoparticles in a hafnium-containing austenitic ODS were characterized. • The nanoparticles are Y–Hf–Ti–O enriched phases according to APT and STEM–EDS. • Two coherency and an axis-parallel orientation relationships were found by HR-TEM. • Particle size has a prominent effect on the orientation relationship (OR). • Formation mechanism of the oxide nanoparticles was discussed based on the ORs.

Manual on the proper use of lutetium-177-labeled somatostatin analogue (Lu-177-DOTA-TATE) injectable in radionuclide therapy (2nd ed.).

Science.gov (United States)

Hosono, Makoto; Ikebuchi, Hideharu; Nakamura, Yoshihide; Nakamura, Nobutaka; Yamada, Takahiro; Yanagida, Sachiko; Kitaoka, Asami; Kojima, Kiyotaka; Sugano, Hiroyasu; Kinuya, Seigo; Inoue, Tomio; Hatazawa, Jun

2018-04-01

Here we present the guideline for the treatment of neuroendocrine tumors using Lu-177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline was prepared by a study supported by Ministry of Health, Labour, and Welfare, and approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown in this guideline are considered internationally useful as well. Only the original Japanese version is the formal document.

A new position-sensitive detector for thermal and epithermal neutrons

International Nuclear Information System (INIS)

Jeavons, A.P.; Ford, N.L.; Lindberg, B.; Sachot, R.

1977-01-01

A new two-dimensional position-sensitive neutron detector is described. It is based on (n,γ) neutron resonance capture in a foil with subsequent detection of internal conversion electrons with a high-density proportional chamber. Large-area detectors with a 1 mm spatial resolution are feasible. A detection efficiency of 50% is possible for thermal neutrons using gadolinium-157 foil and for epithermal neutrons using hafnium-177. (Auth.)

Lutetium 177-Labeled Cetuximab Evaluation for Radioimmunotherapeutic Applications

Directory of Open Access Journals (Sweden)

Kamal Yavari

2012-06-01

Full Text Available Background & Objectives: The monoclonal antibody cetuximab binds to EGFR and thus provides an opportunity to create both imaging and therapeutic modalities that target this receptor. The potential of cetuximab as a radioimmunoconjugate was investigated and quality control tests (in vitro and in vivo were performed as a first step in the production of a new radiopharmaceutical.   Methods : Cetuximab solution was dialyzed and concentrated using an Amicon Ultra-15 filter. Purified antibody was labeled with lutetium-177 using the acyclic bifunctional chelator, DOTA-NHS, and radioimmunoconjugates were purified by PD10 columns. Radiochemical purity and stability in buffer and human blood serum were determined using thin layer chromatography. Integrity of the radiolabeled complex was checked by SDS-PAGE. Preliminary biodistribution studies in normal mice model performed to determine radioimmunoconjugates distribution up to 72h.   Results: The radiochemical purity of the complex was 98±1%. The stabilities in phosphate buffer and in human blood serum at 96 hours post-preparation were 96±2 % and 78±4%, respectively. All of the samples, controls and radiolabeled antibodies, showed a similar pattern of migration in the gel electrophoresis. Biodistribution of Lu177-cetuximab was evaluated in normal mice and the highest ID/g% was observed in the blood (13.2±1.3% at 24 hours and the liver (9.1±1.3% at 24 hours.   Conclusion: Our results show that DOTA-cituximab can be labeled with 177Lu. Lu177-cetuximab has sufficient stability and retains its integrity. The new complex could be considered for further evaluation in animals and possibly in humans as a new radiopharmaceutical for use in radioimmunotherapy of cancers.

21 CFR 177.2470 - Polyoxymethylene copolymer.

Science.gov (United States)

2010-04-01

... Components of Articles Intended for Repeated Use § 177.2470 Polyoxymethylene copolymer. Polyoxymethylene copolymer identified in this section may be safely used as an article or component of articles intended for... are available from the Center for Food Safety and Applied Nutrition (HFS-200), Food and Drug...

[{sup 177}Lu]pertuzumab: experimental studies on targeting of HER-2 positive tumour cells

Energy Technology Data Exchange (ETDEWEB)

Persson, Mikael; Gedda, Lars [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Experimental Urology, Rudbeck Laboratory, Uppsala (Sweden); Tolmachev, Vladimir; Andersson, Karl; Carlsson, Joergen [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Sandstroem, Mattias [Uppsala University, Medical Radiation Physics, Uppsala University Hospital, Uppsala (Sweden)

2005-12-01

The new antibody pertuzumab (Omnitarg) targets the dimerisation subdomain of HER-2. The purpose of this study was to analyse whether pertuzumab retains HER-2 targeting capacity after labelling with the therapeutically interesting beta emitter {sup 177}Lu and to make initial characterisations in vitro and in vivo. Pertuzumab was conjugated with isothiocyanate-benzyl-CHX-A{sup ''}-DTPA and chelated to {sup 177}Lu. Immunoreactivity, affinity, cellular retention and internalisation were analysed using SKOV-3 cells. The affinity of non-radioactive pertuzumab was measured using a surface plasmon resonance biosensor. In vivo targeting and specific binding were assessed in Balb/c (nu/nu) mice carrying SKOV-3 xenografts. The biodistribution of {sup 177}Lu was determined 1, 3 and 7 days after [{sup 177}Lu]pertuzumab administration. Gamma camera images were taken after 3 days. The immunoreactivity of [{sup 177}Lu]pertuzumab was 85.8{+-}1.3%. The affinity of non-radioactive pertuzumab was 1.8{+-}1.1 nM, and that of [{sup 177}Lu]pertuzumab, 4.1{+-}0.7 nM. The cellular retention after 5 h pre-incubation was 90{+-}2% at 20 h. The targeting was HER-2 specific both in vitro and in vivo, since excess amounts of non-labelled antibody inhibited the uptake of labelled antibody (p<0.0001 and p<0.01, respectively). The biodistribution and gamma camera images of {sup 177}Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake. Pertuzumab was efficiently labelled with {sup 177}Lu and showed good intracellular retention and HER-2 specific binding both in vitro and in vivo. The gamma camera images and the biodistribution study gave excellent tumour targeting results. Thus, [{sup 177}Lu]pertuzumab is of interest for further studies aimed at radionuclide therapy. (orig.)

Hafnium oxide nanoparticles: toward an in vitro predictive biological effect?

International Nuclear Information System (INIS)

Marill, Julie; Anesary, Naeemunnisa Mohamed; Zhang, Ping; Vivet, Sonia; Borghi, Elsa; Levy, Laurent; Pottier, Agnes

2014-01-01

Hafnium oxide, NBTXR3 nanoparticles were designed for high dose energy deposition within cancer cells when exposed to ionizing radiation. The purpose of this study was to assess the possibility of predicting in vitro the biological effect of NBTXR3 nanoparticles when exposed to ionizing radiation. Cellular uptake of NBTXR3 nanoparticles was assessed in a panel of human cancer cell lines (radioresistant and radiosensitive) by transmission electron microscopy. The radioenhancement of NBTXR3 nanoparticles was measured by the clonogenic survival assay. NBTXR3 nanoparticles were taken up by cells in a concentration dependent manner, forming clusters in the cytoplasm. Differential nanoparticle uptake was observed between epithelial and mesenchymal or glioblastoma cell lines. The dose enhancement factor increased with increase NBTXR3 nanoparticle concentration and radiation dose. Beyond a minimum number of clusters per cell, the radioenhancement of NBTXR3 nanoparticles could be estimated from the radiation dose delivered and the radiosensitivity of the cancer cell lines. Our preliminary results suggest a predictable in vitro biological effect of NBTXR3 nanoparticles exposed to ionizing radiation

Lutetium-177 complexation of DOTA and DTPA in the presence of competing metals

International Nuclear Information System (INIS)

Watanabe, Satoshi; Ishioka, Noriko S.; Hashimoto, Kazuyuki

2013-01-01

177 Lu complexation of DOTA and DTPA is investigated by the addition of Ca(II), Fe(II) and Zn(II). The 177 Lu complexation yield of DTPA was higher than that of DOTA in the presence of Ca(II), Fe(II) and Zn(II). Therefore, it was found that the 177 Lu complexation of DTPA was more advantageous compared with DOTA in the presence of competing metals, Ca, Fe and Zn. (author)

21 CFR 177.2440 - Polyethersulfone resins.

Science.gov (United States)

2010-04-01

... Components of Articles Intended for Repeated Use § 177.2440 Polyethersulfone resins. Polyethersulfone resins identified in paragraph (a) of this section may be safely used as articles or components of articles intended... Petition Control (HFS-215), Center for Food Safety and Applied Nutrition, 1110 Vermont Ave. NW., suite 1200...

Emergence and present status of Lu-177 in targeted radiotherapy. The Indian scenario

Energy Technology Data Exchange (ETDEWEB)

Banerjee, S.; Das, T.; Chakraborty, S.; Venkatesh, M. [Bhabha Atomic Reseach Centre, Trombay, Mumbai (India). Radiopharmaceuticals Div.

2012-07-01

{sup 177}Lu is presently considered to be a potential radionuclide for the development of agents for radionuclide therapy owing to its favorable nuclear decay characteristics [T{sub 1/2} = 6.65 d, E{sub {beta}}{sub (max)} = 0.497 MeV, E{sub {gamma}} = 113 KeV (6.4%) and 208 KeV (11%)]. While the long half-life of this promising radioisotope offers distinct logistic advantage, particularly, in countries having limited reactor facilities, the feasibility of its large-scale production with adequate specific activity and excellent radionuclidic purity in medium flux research reactors constitute yet another desirable feature. Extensive studies have been carried out to optimize the production of this isotope, with high specific activity and radionuclidic purity by the (n,{gamma}) route using the highest available flux and the optimum irradiation time. The gradual evolution of clin ical grade {sup 177}LuCl{sub 3} as a new radiochemical, ready for commercial deployment by Radiopharmaceuticals Division, Bhabha Atomic Research Centre, to nuclear medicine centers all over India was accomplished in 2010 in a stepwise manner with the commencement of the production of high specific activity {sup 177}Lu from enriched target in 2001. Research on {sup 177}Lu has demonstrated its immense potential in radiotherapeutic applications, a direct outcome of which has resulted in indigenous development of two agents viz. {sup 177}Lu-EDTMP and {sup 177}Lu-DOTA-TATE presently being evaluated in human patients for palliative care of bone pain due to skeletal metastases and treatment of malignancies of neuroendocrine origin, respectively. Using locally produced {sup 177}Lu, the radiolabeling of a plethora of other molecules with potential applicability in radiation synovectomy and targeted therapy of malignant tumors have been successfully demonstrated. A few of these agent such as a novel {sup 177}Lu-labeled porphyrin has shown considerable promise in initial studies and is presently evaluated

Production and Quality Control of 177Lu-Dotatate [177Lu-dota- try3]-Octreotate: Clinical Application

International Nuclear Information System (INIS)

Barboza, M.F. de; Herrerias, R.; Souza, A.A. de; Pereira, G.; Pires, J.A.; Fukumori, N.T.O.; Matsuda, M.M.N.; Almeida, E.V.; Mengatti, J.; Belfer, A.J.; Hilario, L.N.

2009-01-01

Introduction: Somatostatin receptors have been identified in different kinds of tumors such as neuroendocrine tumors and tumors of the central nervous system, breast, lung and lymphatic tissue making these receptors potential targets for radionuclide diagnostics and therapy. These observations have served as the biomolecular basis for the clinical use of radiolabeled somatostatin analogues which, at present, are of great interest in nuclear medicine for diagnostic and peptide receptor radionuclide therapy (PRRT) applications. There are only a few treatment modalities for metastasized neuroendocrine gastroenteropancreatic (GEP) tumors. Besides surgery, (chemo)-embolization, chemotherapy, and treatment with somatostatin (SST) analogs, peptide receptor radionuclide therapy (PRRT) offers therapeutic strategy, as the majority of GEP tumors possess somatostatin receptors (SSTRs). Somatostatin analogs featuring a DOTA-chelator can be radiolabeled with the β-emitters radioisotopes, Yttrium-90 ( 90 Y) and Lutetium-177 ( 177 Lu) for PRRT. Analogs frequently used for therapy are: [DOTA-Tyr 3 ]-octreotide and [DOTA-Tyr 3 ]octreotate. In the latter compound, the alcohol threoninol at the C-terminal of the octreotide has been replaced by the natural threonin amino acid. This alteration resulted in an analog: (Tyr 3 -octreotate), which showed increased affinity for sst2, compared to both [Tyr 3 ]-octreotide and [Phe 1 ]octreotide 'in-vitro' and 'in-vivo'. Clinical studies in patients with different SST-positives tumors proved advantages of [ 177 Lu- DOTA-Tr 3 ]-octreate for therapy. PRRT with radiolabeled somatostatin analogs was shown to be effective in patients with SST2-positive-size reduction, improving quality of life and survival. Objective: The aim of this work was to present the production and the quality control of 177 Lu-Tyr 3 ---octreotate, using DOTA (1,4,7,10-tetrazacyclododecane-N,N',N',N''-tetra acetic acid) as chelating agent at the Radiopharmacy Directory, IPEN

Nano-scale Radiotherapy-NBTXR3 Hafnium Oxide Nanoparticles as Promising Cancer Therapy

International Nuclear Information System (INIS)

Maggiorella, L.; Barouch, G.; Devaux, C.; Pottier, A.; Levy, L.; Deutsch, E.; Bourhis, J.; Borghi, E.

2011-01-01

Complete text of publication follows: Background: There is considerable interest in approaches that could improve the therapeutic window of radiotherapy, which represents a crucial modality of treatment in oncology. We present the rationale for designing NBTXR3 nanoparticles activated by radiotherapy and validate the concept. We performed the Monte Carlo calculations for the first time based on the 'local model' simulation that showed a dose enhancement of radiation to tumour cells of approximately nine-fold. NBTXR3 was shown to deposit high energy when the ionizing radiation source is 'on' and to have chemically inert behavior in cellular and subcellular systems demonstrated by very good systemic tolerance, thus decreasing potential health hazards. Material and Methods: We used conventional methods, implemented in different ways, to explore interactions of high Z matter and ionizing radiation with biological systems. In addition, microtomography was performed to explore the nanoparticle volume occupancy inside the tumour and its persistence overtime in mouse tumour models. The antitumour activity of NBTXR3 and tolerance were evaluated in Ewing tumour (A673) and fibrosarcoma (HT1080) using high energy source. Results and Conclusion: We created and developed NBTXR3 nanoparticles with a crystalline hafnium oxide core which provide high electron density structure and inert behavior in biological media. NBTXR3 nanoparticles' characteristics, size, charge and shape, allow for efficient interaction with biological entities, cell membrane binding and cellular uptake. The nanoparticles were shown to form clusters at the subcellular level in tumour models. Of most importance, we show NBTXR3 intra-tumour bioavailability with dispersion of nanoparticles in the three dimensions and persistence within the tumour structure, supporting the use of NBTXR3 as effective antitumour therapeutic agent. Antitumour activity of NBTXR3 showed marked advantage in terms of survival, tumour

[{sup 177}Lu]DOTA-anti-CD20: Labeling and pre-clinical studies

Energy Technology Data Exchange (ETDEWEB)

Audicio, Paola F., E-mail: paudicio@cin.edu.u [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Castellano, Gustavo, E-mail: gcas@famaf.unc.edu.a [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, 5016 Cordoba (Argentina); Tassano, Marcos R.; Rezzano, Maria E.; Fernandez, Marcelo [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Riva, Eloisa [Clinica Hematologica ' Prof. Dra. L. Diaz' , Hospital de Clinicas. Av. Italia. sn, Montevideo (Uruguay); Robles, Ana; Cabral, Pablo; Balter, Henia; Oliver, Patricia [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay)

2011-07-15

Anti-CD20 (Rituximab), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with {sup 177}Lu through a simple method. [{sup 177}Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [{sup 177}Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.

Reducing renal uptake of 9Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

International Nuclear Information System (INIS)

Miao Yubin; Fisher, Darrell R.; Quinn, Thomas P.

2006-01-01

Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys 3,4,1 , D-Phe 7 , Arg 11 ]α-melanocyte stimulating hormone 3-13 {DOTA-Re(Arg 11 )CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu 2 , Arg 11 )CCMSH was designed, synthesized and labeled with 9 Y and 177 Lu. Pharmacokinetics of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH exhibited significantly (P 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH were 28.16% and 28.81% of those of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH displayed higher tumor-to-kidney uptake ratios than 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was 2.28 and 1.69 times of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. The 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma

Tumoral fibrosis effect on the radiation absorbed dose of 177Lu-Tyr3-octreotate-gold nanoparticles and 177Lu-Tyr3-octreotate radiopharmaceuticals

International Nuclear Information System (INIS)

Zambrano R, O. D.

2015-01-01

In this work was comparatively evaluated the effect of tumoral fibrosis in the radiation absorbed dose of the radiopharmaceutical 177 Lu-Tyr 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 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 ( 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). To this spectrum

A fast response hafnium selective polymeric membrane electrode based on N,N'-bis({alpha}-methyl-salicylidene)-dipropylenetriamine as a neutral carrier

Energy Technology Data Exchange (ETDEWEB)

Rezaei, B. [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)], E-mail: rezaei@cc.iut.ac.ir; Meghdadi, S.; Zarandi, R. Fazel [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

2008-08-30

In this study a new hafnium selective sensor was fabricated from polyvinylchloride (PVC) matrix membrane containing neutral carrier N,N'-bis({alpha}-methyl-salicylidene)-dipropylenetriamine (Mesaldpt) as a new ionophore, sodium tetraphenyl borate (NaTPB) as anionic discriminator and dioctyl phthalate (DOP) as plasticizing solvent mediator in tetrahydrofuran solvent. The electrode exhibits Nernstian response for Hf{sup 4+} (Hafnium(IV)) over a wide concentration range (2.0 x 10{sup -7} to 1.0 x 10{sup -1} M) with the determination coefficient of 0.9966 and slope of 15.1 {+-} 0.1 mV decades{sup -1}. The limit of detection is 1.9 x 10{sup -7} M. The electrode has a fast response time of 18 s and a working pH range of 4-8. The proposed membrane shows excellent discriminating ability towards Hf{sup 4+} ion with regard to several alkali, alkaline earth transition and heavy metal ions. It can be used over a period of 1.5 months with good reproducibility. It is successfully applied for direct determination of Hf{sup 4+} in solutions by standard addition method for real sample analysis.

Lutetium-177 - Broad Production Capabilities are Expected to Stimulate Clinical Applications of this Important Therapeutic Radioisotope

International Nuclear Information System (INIS)

Knapp, F.F. Jr.

2009-01-01

Lutetium-177 (Lu-177) is of broad interest for therapeutic applications where the deposition of localized radiation can benefit from the limited soft tissue penetration of the 0.497 MeV beta particle (max. = 2.76 mm). Examples of Lu-177 therapeutic strategies include treatment of small SS2/SS5-expressing tumors with targeted peptides and radiosynovectomy. Emission of a 208 keV gamma photon (11 %) allows imaging for evaluation of localization and biokinetics, and for targeting applications, correlation of uptake with therapeutic response. A broad spectrum of research reactors with even modest thermal neutron flux (e.g. > 1 x 10 14 ) can produce carrier-added Lu-177 with sufficient specific activity (SA) > 10 Ci/mg Lu by the 'direct' approach by irradiation of Lu-176. For low SA applications, thermal flux of > 10 13 in low-medium flux reactors provides sufficient SA (> 0.5 mCi Lu-177/mg) for preparation of Lu-EDTMP for synovectomy. Although relative Lu-177m/Lu-177 activity levels from 'direct' production can be very low (> 10 -5 ), the Lu-177m impurity levels can present an issue with radioactive waste storage requirements at some institutions. The alternative 'indirect' approach using decay of reactor produced ytterbium-177 available from by neutron irradiation of enriched Yb-176 targets provides no-carrier-added (nca) Lu-177 (theoretical SA = 109 Ci/mg Lu). Purification of the microscopic levels of nca Lu-177 from macroscopic Yb levels at the high multi Curie production level is a more challenging approach, since production yields are relatively low even at high thermal flux (e.g. 2 x 10 15 neutrons/cm 2 /sec). In addition, high mass Lu/Yb separation is especially time consuming, can generate significant waste, and the relatively expensive Yb-176 target material (> 97%, ∼ $ 20/mg) must be recovered, re-purified and used for subsequent target preparation. However, a number of effective methods for the Lu/Yb separation and Yb recovery have been reported, and even

Hafnium-doped hydroxyapatite nanoparticles with ionizing radiation for lung cancer treatment.

Science.gov (United States)

Chen, Min-Hua; Hanagata, Nobutaka; Ikoma, Toshiyuki; Huang, Jian-Yuan; Li, Keng-Yuan; Lin, Chun-Pin; Lin, Feng-Huei

2016-06-01

Recently, photodynamic therapy (PDT) is one of the new clinical options by generating cytotoxic reactive oxygen species (ROS) to kill cancer cells. However, the optical approach of PDT is limited by tissue penetration depth of visible light. In this study, we propose that a ROS-enhanced nanoparticle, hafnium-doped hydroxyapatite (Hf:HAp), which is a material to yield large quantities of ROS inside the cells when the nanoparticles are bombarded with high penetrating power of ionizing radiation. Hf:HAp nanoparticles are generated by wet chemical precipitation with total doping concentration of 15mol% Hf(4+) relative to Ca(2+) in HAp host material. The results show that the HAp particles could be successfully doped with Hf ions, resulted in the formation of nano-sized rod-like shape and with pH-dependent solubility. The impact of ionizing radiation on Hf:HAp nanoparticles is assessed by using in-vitro and in-vivo model using A549 cell line. The 2',7'-dichlorofluorescein diacetate (DCFH-DA) results reveal that after being exposed to gamma rays, Hf:HAp could significantly lead to the formation of ROS in cells. Both cell viability (WST-1) and cytotoxicity (LDH) assay show the consistent results that A549 lung cancer cell lines are damaged with changes in the cells' ROS level. The in-vivo studies further demonstrate that the tumor growth is inhibited owing to the cells apoptosis when Hf:HAp nanoparticles are bombarded with ionizing radiation. This finding offer a new therapeutic method of interacting with ionizing radiation and demonstrate the potential of Hf:HAp nanoparticles in tumor treatment, such as being used in a palliative treatment after lung surgical procedure. Photodynamic therapy (PDT) is one of the new clinical options by generating cytotoxic reactive oxygen species (ROS) to kill cancer cells. Unfortunately, the approach of PDT is usually limited to the treatment of systemic disease and deeper tumor, due to the limited tissue penetration depth of visible

21 CFR 177.1211 - Cross-linked polyacrylate copolymers.

Science.gov (United States)

2010-04-01

... Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1211 Cross-linked polyacrylate... shall be determined using size exclusion chromatography or an equivalent method. When conducting the...

Reference: 177 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 177 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u4ria224u15722472i Al-Daoude ...lator of the plant disease resistance protein RPM1. 3 1016-28 15722472 2005 Mar The Plant cell Al-Daoude Antonious|Grant Murray|Ko Jong-Hyun|de Torres Zabala Marta

Sub-10 nm low current resistive switching behavior in hafnium oxide stack

Energy Technology Data Exchange (ETDEWEB)

Hou, Y., E-mail: houyi@pku.edu.cn, E-mail: lfliu@pku.edu.cn [Institute of Microelectronics, Peking University, 100871 Beijing (China); IMEC, Kapeldreef 75, B-3001 Heverlee (Belgium); Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D, B-3001 Heverlee (Belgium); Celano, U.; Xu, Z.; Vandervorst, W. [IMEC, Kapeldreef 75, B-3001 Heverlee (Belgium); Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D, B-3001 Heverlee (Belgium); Goux, L.; Fantini, A.; Degraeve, R.; Youssef, A.; Jurczak, M. [IMEC, Kapeldreef 75, B-3001 Heverlee (Belgium); Liu, L., E-mail: houyi@pku.edu.cn, E-mail: lfliu@pku.edu.cn; Cheng, Y.; Kang, J. [Institute of Microelectronics, Peking University, 100871 Beijing (China)

2016-03-21

In this letter, a tip-induced cell relying on the conductive atomic force microscope is proposed. It is verified as a referable replica of an integrated resistive random access memory (RRAM) device. On the basis of this cell, the functionality of sub-10 nm resistive switching is confirmed in hafnium oxide stack. Moreover, the low current switching behavior in the sub-10 nm dimension is found to be more pronounced than that of a 50 × 50 nm{sup 2} device. It shows better ON/OFF ratio and low leakage current. The enhanced memory performance is ascribed to a change in the shape of the conductive filament as the device dimensions are reduced to sub-10 nm. Therefore, device downscaling provides a promising approach for the resistance optimization that benefits the RRAM array design.

9 CFR 381.177 - Record retention period.

Science.gov (United States)

2010-01-01

... Section 381.177 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY... such record under this subpart. (b) Records of canning as required by subpart X of this part 381...

Labelling of the peptide Dota-Octreotate with Lutetium 177

International Nuclear Information System (INIS)

Hernandez B, C.A.

2004-01-01

In this work is described the optimization of the reaction conditions to obtain the complex 177 Lu-Dota-TATE with a radiochemical purity > 95%, even so the studies of stability In vitro to the dilution in saline solution, stability in human serum and challenge to the cystein. The biodistribution studies are presented in mice Balb-C and the tests of biological recognition using one lines cellular of pancreatic adenoma (AR42-J). The obtained results show a high stability of the radio complex in vitro, since it doesn't suffer trans chelation from the Lutetium-177 to plasmatic proteins. The biodistribution tests in mice Balb-C demonstrated an appropriate lipophilly of the complex to be excreted in more proportion by the kidneys without significant accumulation in healthy tissues. It is necessary to mention that the drop activity specifies (3.54 μg / 37 MBq) obtained in the irradiation of 176 Lu 2 O 3 it allowed to verify the union of the 177 Lu-Dota-Tate to membrane receivers but without being able to obtain the saturation curves and competition required to characterize quantitatively the biological recognition. (Author)

Separation of hafnium from zirconium in their tetrachloride solution in molten alkali metal chlorides

Energy Technology Data Exchange (ETDEWEB)

Salyulev, A B; Kudyakov, V Ya; Smirnov, M V; Moskalenko, N I [AN SSSR, Sverdlovsk. Inst. Ehlektrokhimii

1984-08-01

The coefficient of HfCl/sub 4/ and ZrCl/sub 4/ separation in the process of vapour sublimation from their solutions in molten NaCl, KCl, CsCl, NaCl-KCl and NaCl-CsCl equimolar mixtures is found to vary in the series from approximately 1.10 to approximately 1.22 and practically not to depend on the temperature (in the 600-910 deg) range and concentration (2-25 mol.% ZrCl/sub 4/+HfCl/sub 4/). HfCl/sub 4/ and ZrCl/sub 4/ are shown to form almost perfect solutions with each other, which in their turn form imperfect solutions with molten alkali metal chlorides, with the strength of hafnium complex chloride anions increasing higher than that of zirconium in the series from NaCl to CsCl.

Separation of hafnium from zirconium in their tetrachloride solution in molten alkali metal chlorides

International Nuclear Information System (INIS)

Salyulev, A.B.; Kudyakov, V.Ya.; Smirnov, M.V.; Moskalenko, N.I.

1984-01-01

The coefficient of HfCl 4 and ZrCl 4 separation in the process of vapour sublimation from their solutions in molten NaCl, KCl, CsCl, NaCl-KCl and NaCl-CsCl equimolar mixtures is found to vary in the series from approximately 1.10 to approximately 1.22 and practically not to depend on the temperature (in the 600-910 deg) range and concentration (2-25 mol.% ZrCl 4 +HfCl 4 ). HfCl 4 and ZrCl 4 are shown to form almost perfect solutions with each other, which in their turn form imperfect solutions with molten alkali metal chlorides, with the strength of hafnium complex chloride anions increasing higher than that of zirconium in the series from NaCl to CsCl

DOTA-TATE peptides labelling with Lutetium 177: Preliminary study

International Nuclear Information System (INIS)

Aliaga, Eleazar; Robles, Anita; Ramos, Bertha; Martinez, Flor

2014-01-01

he peptide DOTA-TATE was labeled with lutetium 177 according to the methodology provided under the regional project RLA/6/074, sponsored by the IAEA. The labeling was done in 0.26 M gentisic acid solution in 0.8 M sodium acetate buffer, pH 5, at 100 °C for 30 minutes in a dry heating block. The radiochemical purity was assessed by thin layer chromatography, using ITLC SG strips and a mixture of 0.15 M ammonium acetate - methanol (1:1) as solvent. The radiolabeled peptide 177 Lu-DOTA-TATE reached a radiochemical purity of 98 % with a specific activity of 2,8 mCi/µg of peptide. (authors).

14 CFR 93.177 - Operations in the Special Air Traffic Rule Area.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Operations in the Special Air Traffic Rule Area. 93.177 Section 93.177 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Special Flight Rules in the Vicinity of Luke AFB, AZ §...

50 CFR 17.7 - Raptor exemption.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 2 2010-10-01 2010-10-01 false Raptor exemption. 17.7 Section 17.7....7 Raptor exemption. (a) The prohibitions found in §§ 17.21 and 17.31 do not apply to any raptor [a... permittee's possession on November 10, 1978, or as the progeny of such a raptor. (b) This section does not...

21 CFR 177.2490 - Polyphenylene sulfide resins.

Science.gov (United States)

2010-04-01

... Components of Articles Intended for Repeated Use § 177.2490 Polyphenylene sulfide resins. Polyphenylene... coatings of articles intended for repeated use in contact with food, in accordance with the following... are available from the Center for Food Safety and Applied Nutrition (HFS-200), Food and Drug...

Image collection: 177 [Togo Picture Gallery[Archive

Lifescience Database Archive (English)

Full Text Available 177 Polypterus_endlicheri_NL.png ポリプテルスエンドリケリ Polypterus endlicheri Polypterus endlicheri 348150 生物アイコン,脊索動物門,脊椎動物亜門,魚上綱

Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

International Nuclear Information System (INIS)

Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

2015-01-01

177 Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177 Lu-EDTMP for MBP palliation. 177 Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177 Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177 Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for

Metastatic Bone Pain Palliation using (177)Lu-Ethylenediaminetetramethylene Phosphonic Acid.

Science.gov (United States)

Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R; Bahrami-Samani, Ali

2015-01-01

(177)Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using (177)Lu-EDTMP for MBP palliation. (177)Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. (177)Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. (177)Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for

Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

Science.gov (United States)

Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

2015-01-01

177Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177Lu-EDTMP for MBP palliation. 177Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients

21 CFR 177.2450 - Polyamide-imide resins.

Science.gov (United States)

2010-04-01

... Components of Articles Intended for Repeated Use § 177.2450 Polyamide-imide resins. Polyamide-imide resins identified in paragraph (a) of this section may be safely used as components of articles intended for... Safety and Applied Nutrition (HFS-200), Food and Drug Administration, 5100 Paint Branch Pkwy., College...

An electro-amalgamation approach to isolate no-carrier-added 177Lu from neutron irradiated Yb for biomedical applications

International Nuclear Information System (INIS)

Chakravarty, Rubel; Das, Tapas; Dash, Ashutosh; Venkatesh, Meera

2010-01-01

Introduction: A novel two-step separation process for the production of no-carrier-added (NCA) 177 Lu from neutron irradiated Yb target through an electrochemical pathway employing mercury-pool cathode has been developed. Methods: A two-cycle electrolysis procedure was adopted for separation of 177 Lu from 177 Lu/Yb mixture in lithium citrate medium. The influence of different experimental parameters on the separation process was investigated and optimized for the quantitative deposition of Yb in presence of 177 Lu. The first electrolysis was performed for 50 min in the 177 Lu/Yb feed solution at pH 6 applying a potential of 8 V using platinum electrode as anode and mercury as the cathode. The second electrolysis was performed under the same conditions using fresh electrodes. The radionuclidic and chemical purity of 177 Lu was determined by using gamma ray spectrometry and atomic absorption spectrometry. The suitability of 177 Lu for biomedical applications was ascertained by labeling 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid D-Phe 1 -Tyr 3 -octreotate(DOTA-TATE) with 177 Lu. Results: This process could provide NCA 177 Lu with >99.99% radionuclidic purity and an overall separation yield of ∼99% was achieved within 3-4 h. The Hg content in the product was determined to be 98% was obtained with DOTA-TATE under the optimized reaction conditions. Conclusions: An efficient strategy for the separation of NCA 177 Lu, suitable for biomedical applications, has been developed.

Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer; Estudo da marcacao e biodistribuicao da substancia P utilizando lutecio-177 como radiotracador

Energy Technology Data Exchange (ETDEWEB)

Lima, Clarice Maria de

2011-07-01

Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with {beta}{sup -} emitting radioisotopes. The Substance P (SP) is an 11- amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH{sub 2}. The use of SP labeled with different radionuclides including {sup 177}Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, over expressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with {sup 177}Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity of lutetium-177 chloride and mass of DOTA-SP. The radiochemical purity of preparations were analyzed by chromatographic techniques. The stability of {sup 17L}u -DOTA- SP radiolabeled with low activity of {sup 177}Lu was evaluated for different time at 2-8 degree C or incubated in human serum. The stability of the labeled with high activity of {sup 177}Lu was also analyzed in the presence of gentisic acid (6 mg / mL) added after the labeling reaction. The labeled conditions in low and high activity were subjected to evaluation for the ability to cause oxidation of methionine residue, adding the D-L- methionine amino acid to the reaction medium (6 mg / mL) and subsequent chromatographic evaluation. In vitro study with {sup 177}Lu

Direct evidence for inelastic neutron 'acceleration' by 177Lum

International Nuclear Information System (INIS)

Roig, O.; Meot, V.; Rosse, B.; Belier, G.; Daugas, J.-M.; Morel, P.; Letourneau, A.; Menelle, A.

2011-01-01

The inelastic neutron acceleration cross section on the long-lived metastable state of 177 Lu has been measured using a direct method. High-energy neutrons have been detected using a specially designed setup placed on a cold neutron beam extracted from the ORPHEE reactor in Saclay. The 146±19 b inelastic neutron acceleration cross section in the ORPHEE cold neutron flux confirms the high cross section for this process on the 177 Lu m isomer. The deviation from the 258±58 b previously published obtained for a Maxwellian neutron flux at a 323 K temperature could be explained by the presence of a low energy resonance. Resonance parameters are deduced and discussed.

An electro-amalgamation approach to isolate no-carrier-added 177Lu from neutron irradiated Yb for biomedical applications.

Science.gov (United States)

Chakravarty, Rubel; Das, Tapas; Dash, Ashutosh; Venkatesh, Meera

2010-10-01

A novel two-step separation process for the production of no-carrier-added (NCA) (177)Lu from neutron irradiated Yb target through an electrochemical pathway employing mercury-pool cathode has been developed. A two-cycle electrolysis procedure was adopted for separation of (177)Lu from (177)Lu/Yb mixture in lithium citrate medium. The influence of different experimental parameters on the separation process was investigated and optimized for the quantitative deposition of Yb in presence of (177)Lu. The first electrolysis was performed for 50 min in the (177)Lu/Yb feed solution at pH 6 applying a potential of 8 V using platinum electrode as anode and mercury as the cathode. The second electrolysis was performed under the same conditions using fresh electrodes. The radionuclidic and chemical purity of (177)Lu was determined by using gamma ray spectrometry and atomic absorption spectrometry. The suitability of (177)Lu for biomedical applications was ascertained by labeling 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid D-Phe(1)-Tyr(3)-octreotate(DOTA-TATE) with (177)Lu. This process could provide NCA (177)Lu with >99.99% radionuclidic purity and an overall separation yield of ∼99% was achieved within 3-4 h. The Hg content in the product was determined to be 98% was obtained with DOTA-TATE under the optimized reaction conditions. An efficient strategy for the separation of NCA (177)Lu, suitable for biomedical applications, has been developed. Copyright © 2010 Elsevier Inc. All rights reserved.

Density and surface tension of melts of zirconium and hafnium fluorides with lithium fluoride

International Nuclear Information System (INIS)

Katyshev, S.F.; Artemov, V.V.; Desyatnik, V.N.

1988-01-01

A study was conducted to determine the temperature dependence of the density and surface tension of melts of LiF-ZrF 4 and LiF-HfF 4 . Density and surface tension were determined by the method of maximum pressure in an argon bubble. On the basis of experimental data over the entire concentration range the molar volumes and their relative deviations from the additive molar volumes were calculated for 1100 0 K. The positive deviations of the molar volumes from additivity in the LiF-HfF 4 system (22.45%) were greater than in the LiF-ZrF 4 system (15.75%). This indicated that the reaction with lithium fluoride is intensified with the switch to the hafnium fluoride. Results also demonstrated that the fluorides are surface-active components in the molten mixtures

Antitenascin antibody 81C6 armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

Energy Technology Data Exchange (ETDEWEB)

Yordanov, Alexander T. [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States); Hens, Marc [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States); Pegram, Charles [Department of Pathology, Duke University Medical Center Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States)]. E-mail: zalut001@mc.duke.edu

2007-02-15

Introduction: When labeled with iodine-131, the antitenascin monoclonal antibody (mAb) 81C6 has shown promise as a targeted radiotherapeutic in patients with brain tumors. Because of its more favorable {gamma}-ray properties, lutetium-177 might be a better low-energy {beta}-emitter for this type of therapy. Materials and Methods: Chimeric 81C6 (ch81C6) was labeled with {sup 177}Lu using the acyclic 1B4M ligand and the macrocyclic ligands NHS-DOTA and MeO-DOTA and evaluated for binding to tenascin. Three paired-label tissue distribution experiments were performed in normal mice receiving one of the {sup 177}Lu-labeled immunoconjugates plus {sup 125}I-labeled ch81C6 labeled using Iodogen. Paired-label experiments in athymic mice bearing subcutaneous D54 MG human glioma xenografts were done to directly compare the biodistribution of ch81C6-1B4M-{sup 177}Lu and {sup 125}I-labeled ch81C6, and ch81C6-MeO-DOTA-{sup 177}Lu and {sup 125}I-labeled ch81C6. Similar comparisons were done using murine (mu) instead of ch81C6. The primary parameter utilized for evaluation was the {sup 177}Lu/{sup 125}I uptake ratio in each tissue. Results: In the studies performed in normal mice, the NHS-DOTA ligand yielded the highest {sup 177}Lu/{sup 125}I uptake ratios in tissues indicative of loss of label from the chelate; for this reason, only 1B4M and MeO-DOTA were evaluated further. The {sup 177}Lu/{sup 125}I ratio in bone increased gradually with time for the chimeric conjugates; however, there were no significant differences between ch81C6-1B4M-DTPA-{sup 177}Lu and ch81C6-MeO-DOTA-{sup 177}Lu. In contrast, mu81C6-1B4M-DTPA-{sup 177}Lu and mu81C6-MeO-DOTA-{sup 177}Lu showed a more dramatic increase in the {sup 177}Lu/{sup 125}I ratio in bone - from 2.4{+-}0.3 and 1.7{+-}0.2 at Day 1 to 8.5{+-}1.1 and 4.2{+-}0.5 at Day 7, respectively. Conclusion: With these antitenascin constructs, the nature of the mAb had a profound influence on the relative degree of loss of {sup 177}Lu from these

Tribo-electrochemical characterization of hafnium multilayer systems deposited on nitride/vanadium nitride AISI 4140 steel

Science.gov (United States)

Mora, M.; Vera, E.; Aperador, W.

2016-02-01

In this work is presented the synergistic behaviour among corrosion/wear (tribocorrosion) of the multilayer coatings hafnium nitride/vanadium nitride [HfN/VN]n. The multilayers were deposited on AISI 4140 steel using the technique of physical vapor deposition PVD magnetron sputtering, the tests were performed using a pin-on-disk tribometer, which has an adapted potentiostat galvanostat with three-electrode electrochemical cell. Tribocorrosive parameters such as: Friction coefficient between the coating and the counter body (100 Cr6 steel ball); Polarization resistance by means of electrochemical impedance spectroscopy technique and corrosion rate by polarization curves were determined. It was observed an increase in the polarization resistance, a decrease in the corrosion rate and a low coefficient of friction in comparison with the substrate, due to an increase on the number of bilayers.

Tribo-electrochemical characterization of hafnium multilayer systems deposited on nitride/vanadium nitride AISI 4140 steel

International Nuclear Information System (INIS)

Mora, M; Vera, E; Aperador, W

2016-01-01

In this work is presented the synergistic behaviour among corrosion/wear (tribocorrosion) of the multilayer coatings hafnium nitride/vanadium nitride [HfN/VN]n. The multilayers were deposited on AISI 4140 steel using the technique of physical vapor deposition PVD magnetron sputtering, the tests were performed using a pin-on-disk tribometer, which has an adapted potentiostat galvanostat with three-electrode electrochemical cell. Tribocorrosive parameters such as: Friction coefficient between the coating and the counter body (100 Cr6 steel ball); Polarization resistance by means of electrochemical impedance spectroscopy technique and corrosion rate by polarization curves were determined. It was observed an increase in the polarization resistance, a decrease in the corrosion rate and a low coefficient of friction in comparison with the substrate, due to an increase on the number of bilayers. (paper)

Rapid screening of nuclear grade zirconium silicate without separation of hafnium from the bulk matrix

International Nuclear Information System (INIS)

Venkatesh, Manisha; Sharma, P.K.; Avhad, D.K.; Basu, H.; Singhal, R.K.; Reddy, A.V.R.

2014-01-01

Zirconium silicate, also zirconium orthosilicate, (ZrSiO 4 ) is a chemical compound, and occurs in nature as zircon, a silicate mineral. The concentration of Hafnium in nuclear grade Zirconium must be less than 0.2% w/w of Zr. In view of this it must be accurately chemically characterized before issuing a certification for export under non nuclear category. As the chemistry of Zr and Hf is similar, it is difficult to separate Hf by direct wet chemical method. During this work, concentration of Hf in zirconium silicate was measured by Field Portable X-ray Fluorescence (FPXRF) and results obtained were validated by using detailed chemical method. FPXRF spectrometry has become a common analytical technique for on-site screening and fast turnaround analysis of contaminant elements in environmental samples

Potential renal toxicity bio-markers indicating radiation injury after 177Lu-octreotate treatment

International Nuclear Information System (INIS)

Dalmo, J.; Forssell-Aronsson, E.; Westberg, E.; Toernqvist, M.; Svedborn, L.; Barregaerd, L.

2015-01-01

Full text of publication follows. The kidneys are one of the most exposed non-tumor tissues and regarded as one of the main dose-limiting organs in peptide receptor radionuclide therapy (PRRT). [ 177 Lu-DOTA0, Tyr3]-octreotate ( 177 Lu-octreotate) has shown promising results in the treatment of somatostatin receptor over-expressing neuroendocrine tumors, but optimization is still needed. The ability to give each patient as much 177 Lu-octreotate as possible without inducing nephrotoxicity is necessary for an efficient treatment. However, due to large inter-individual differences in uptake and retention in the kidneys, there is a need for efficient methods that can indicate renal injury early. A possible way is to identify bio-markers for high risk of radiation nephrotoxicity. The aim of this study was to investigate the potential of using urinary retinol binding protein (RBP), and blood valinhydantoin (VH) as bio-markers of nephrotoxicity on adult mice after 177 Lu-octreotate treatment. BALB/c nude mice (n=6/group) were i.v. injected with 60 MBq or 120 MBq of 177 Lu-octreotate. The control group was mock treated with saline. Spot urine samples were collected before injection, and 14, 30, 60 and 90 days after injection. Analysis of RBP4 and creatinine was performed using Mouse RBP4 ELISA kit and Creatinine kit from R/D Systems, respectively. Erythrocytes were separated from whole blood samples collected 90 days after injection, and analysed for VH by LC-MS/MS. The ratio between VH and a volumetric standard was calculated. The RBP/creatinine level increased with time in both groups given 177 Lu-octreotate, with earlier and higher response for the 120 MBq group. No clear change in VH level between the different groups was observed. The results show that RBP may be a promising new bio-marker for radiation induced kidney toxicity. The presently used method based on VH was not sensitive enough to be used as kidney toxicity marker. Further studies on mice are ongoing to

Development of a therapeutic radiopharmaceutical {sup 177}Lu-DOTA- Minigastrin for potential use in PRRT; Desarrollo de un radiofarmaco terapeutico {sup 177}Lu-DOTA-Minigastrina para su potencial uso en PRRT

Energy Technology Data Exchange (ETDEWEB)

Lopez Bularte, A. C.; Nevares, N. N.; Zapata, A. M.; Perez, J. H.; Crudo, J. L. [Comision Nacional de Energia Atomica (Argentina); Puerta Yepes, N.; Rojo, A. M. [Autoridad Regulatoria Nuclear (Argentina)

2010-07-01

The aim of this work is to obtain {sup 177}Lu-DOTA-Minigastrin with high radiochemical purity (RP) and the highest specific activity (Ae) as possible, using a locally produced (Nuclear Reactor RA-3, Ezeiza Atomic Center) {sup 177}LuCl{sub 3} of an intermediate level of Ae (between 6.36 to 17.95 Ci/mg of {sup 176}Lu) ) and also to perform in vitro and in vivo stability tests, dose calculation in normal mice and its extrapolation to a human model. (authors) [Spanish] El objetivo de este trabajo consistio en obtener {sup 177}Lu-DOTA-Minigastrina con una alta pureza radioquimica (PR) y la mayor actividad especifica (Ae) posible, empleando {sup 177}LuCl{sub 3} de media Ae (entre 6,36-17,95 Ci/mg de {sup 176}Lu) de produccion local (Reactor Nuclear RA-3, Centro Atomico Ezeiza), y realizar los ensayos de estabilidad in vitro e in vivo, el calculo de dosis en ratones normales y su extrapolacion a un modelo humano. (autores)

Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

International Nuclear Information System (INIS)

Edler von Eyben, Finn; Roviello, Giandomenico; Kiljunen, Timo; Kairemo, Kalevi; Joensuu, Timo; Uprimny, Christian; Virgolini, Irene

2018-01-01

There is a controversy as to the relative efficacy of 177 Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177 Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. Twelve studies including 669 patients reported 177 Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with 177 Lu-PSMA RLT. The treatment with 177 Lu-PSMA-617 and 177 Lu-PSMA for imaging and therapy (I and T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. 177 Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). 177 Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ 2 test). Median survival was longer after 177 Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for 177 Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ 2 test). As for patients with mCRPC, treatment with 177 Lu

The research on biodistribution of bearing sarcoma mice and rabbit SPECT imaging of 177Lu-DOTMP

International Nuclear Information System (INIS)

Deng Xinrong; Xiang Xueqin; Li Fenglin; Fan Caiyun; Liu Zihua; Luo Zhifu; Chen Yang

2012-01-01

Cyclen (1, 4, 7, 10-tetraazacyclododecane) and H 3 PO 3 were used to synthesis DOTMP (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-Tetraaminomethylenephosphonate), and then DOTMP was labelled with 177 Lu. The research of biodistribution of 177 Lu-DOTMP in model mice bearing S180 sarcoma and SPECT imaging in Japanese white rabbit were also carried out. The results of biodistribution of bearing S180 mice indicated that 177 Lu-DOTMP cleared rapidly from blood and was selectively delivered to target bone. The radioactivity uptake was mainly in bone and less in other organs and tissues. The results of SPECT imaging of Japanese white rabbit showed that the radioactivity was accumulated in bladder. 177 Lu-DOTMP was mainly excreted by kidney. The uptake of the activity in the skeleton was observed significantly within 22 h post-injection and it became quite significant at 46 h post-injection. It indicated that 177 Lu-DOTMP has good bone targeting and is worthy of further study. (authors)

Hafnium Films and Magnetic Shielding for TIME, A mm-Wavelength Spectrometer Array

Science.gov (United States)

Hunacek, J.; Bock, J.; Bradford, C. M.; Butler, V.; Chang, T.-C.; Cheng, Y.-T.; Cooray, A.; Crites, A.; Frez, C.; Hailey-Dunsheath, S.; Hoscheit, B.; Kim, D. W.; Li, C.-T.; Marrone, D.; Moncelsi, L.; Shirokoff, E.; Steinbach, B.; Sun, G.; Trumper, I.; Turner, A.; Uzgil, B.; Weber, A.; Zemcov, M.

2018-04-01

TIME is a mm-wavelength grating spectrometer array that will map fluctuations of the 157.7-μm emission line of singly ionized carbon ([CII]) during the epoch of reionization (redshift z ˜ 5-9). Sixty transition-edge sensor (TES) bolometers populate the output arc of each of the 32 spectrometers, for a total of 1920 detectors. Each bolometer consists of gold absorber on a ˜ 3 × 3 mm silicon nitride micro-mesh suspended near the corners by 1 × 1 × 500 μm silicon nitride legs targeting a photon-noise-dominated NEP ˜ 1 × 10^{-17} W/√{Hz} . Hafnium films are explored as a lower-T_c alternative to Ti (500 mK) for TIME TESs, allowing thicker support legs for improved yield. Hf T_c is shown to vary between 250 and 450 mK when varying the resident Ar pressure during deposition. Magnetic shielding designs and simulations are presented for the TIME first-stage SQUIDs. Total axial field suppression is predicted to be 5 × 10^7.

Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn–177Lu is superior to 90Y–177Lu in peptide receptor radiotherapy

International Nuclear Information System (INIS)

Walrand, Stephan; Hanin, François-Xavier; Pauwels, Stanislas; Jamar, François

2012-01-01

Clinical trials on 177 Lu– 90 Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace 90 Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1–25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for 93 Y, 90 Y and 125 Sn in combination with 177 Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75–25% combination of 177 Lu and 90 Y activity. However, 125 Sn– 177 Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. 125 Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics 125 Sn is the best RN for combination with 177 Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of 125 Sn-labelled somatostatin analogues. (paper)

Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

International Nuclear Information System (INIS)

Romer, A.; Seiler, D.; Brunner, P.; Ng, Q.K.T.; Mueller-Brand, J.; Marincek, N.; Walter, M.A.; Koller, M.T.; Maecke, H.R.; Rochlitz, C.; Briel, M.; Schindler, C.

2014-01-01

Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90 Y or 177 Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [ 90 Y-DOTA]-TOC or [ 177 Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [ 90 Y-DOTA]-TOC and 141 patients underwent 259 cycles of [ 177 Lu-DOTA]-TOC. The median survival after [ 177 Lu-DOTA]-TOC and after [ 90 Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [ 177 Lu-DOTA]-TOC over [ 90 Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [ 177 Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [ 177 Lu-DOTA]-TOC and [ 90 Y-DOTA]-TOC. Furthermore, [ 177 Lu-DOTA]-TOC was less haematotoxic than [ 90 Y-DOTA]-TOC. (orig.)

Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours.

Science.gov (United States)

Romer, A; Seiler, D; Marincek, N; Brunner, P; Koller, M T; Ng, Q K T; Maecke, H R; Müller-Brand, J; Rochlitz, C; Briel, M; Schindler, C; Walter, M A

2014-02-01

Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y-DOTA]-TOC or [(177)Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [(90)Y-DOTA]-TOC and 141 patients underwent 259 cycles of [(177)Lu-DOTA]-TOC. The median survival after [(177)Lu-DOTA]-TOC and after [(90)Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95% confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [(177)Lu-DOTA]-TOC over [(90)Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [(177)Lu-DOTA]-TOC treatment (1.4 vs 10.1%, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8%, p = 0.32). The present results revealed no difference in median overall survival after [(177)Lu-DOTA]-TOC and [(90)Y-DOTA]-TOC. Furthermore, [(177)Lu-DOTA]-TOC was less haematotoxic than [(90)Y-DOTA]-TOC.

177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

Directory of Open Access Journals (Sweden)

Ada H V Repetto-Llamazares

Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

An electro-amalgamation approach to isolate no-carrier-added {sup 177}Lu from neutron irradiated Yb for biomedical applications

Energy Technology Data Exchange (ETDEWEB)

Chakravarty, Rubel; Das, Tapas [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Dash, Ashutosh, E-mail: adash@barc.gov.i [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Venkatesh, Meera [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

2010-10-15

Introduction: A novel two-step separation process for the production of no-carrier-added (NCA) {sup 177}Lu from neutron irradiated Yb target through an electrochemical pathway employing mercury-pool cathode has been developed. Methods: A two-cycle electrolysis procedure was adopted for separation of {sup 177}Lu from {sup 177}Lu/Yb mixture in lithium citrate medium. The influence of different experimental parameters on the separation process was investigated and optimized for the quantitative deposition of Yb in presence of {sup 177}Lu. The first electrolysis was performed for 50 min in the {sup 177}Lu/Yb feed solution at pH 6 applying a potential of 8 V using platinum electrode as anode and mercury as the cathode. The second electrolysis was performed under the same conditions using fresh electrodes. The radionuclidic and chemical purity of {sup 177}Lu was determined by using gamma ray spectrometry and atomic absorption spectrometry. The suitability of {sup 177}Lu for biomedical applications was ascertained by labeling 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid D-Phe{sup 1}-Tyr{sup 3}-octreotate(DOTA-TATE) with {sup 177}Lu. Results: This process could provide NCA {sup 177}Lu with >99.99% radionuclidic purity and an overall separation yield of {approx}99% was achieved within 3-4 h. The Hg content in the product was determined to be <1 ppm. Radiolabeling yield of >98% was obtained with DOTA-TATE under the optimized reaction conditions. Conclusions: An efficient strategy for the separation of NCA {sup 177}Lu, suitable for biomedical applications, has been developed.

Primary standardization of a {sup 177}Lu solution; Padronizacao primaria de uma solucao de {sup 177}Lu

Energy Technology Data Exchange (ETDEWEB)

Iwahara, Akira; Silva, Carlos Jose da; Tauhata, Luiz; Oliveira, Estela Maria de, E-mail: iwahara@ird.gov.b, E-mail: carlos@ird.gov.b, E-mail: tauhata@ird.gov.b, E-mail: estela@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Rezende, Eduarda Alexandre, E-mail: eduarda@ird.gov.b [Centro Federal de Educacao Tecnologica de Quimica (CEFET), Nilopolis, RJ (Brazil)

2009-07-01

For the purpose to make available reliable standards of {sup 177}Lu to the users and producers, a radionuclide solution was standardized using the primary methods of coincidence 4{pi}{beta}(PC)-{gamma}(NaI(Tl)) and of 4{pi}{beta}(LS)-{gamma}(NaI(Tl)). The results presented a convergence in the range of evaluated uncertainties. The standard uncertainties were of the 0.50 and 0.74% for the anticoincidence and coincidence respectively

68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

Science.gov (United States)

Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

2017-06-01

Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

A spanish mineral of zirconium and hafnium. Separation of the two elements by liquid-liquid extraction, using tributyl phosphate as chelating agent

International Nuclear Information System (INIS)

Ruiz Sanchez, F.; Cruz Castillo, F. de la; Fernandez Cellini, R.

1962-01-01

The zirconium and Hafnium oxides are obtained from a Spanish mineral of zircon with an average contest of 55% in ZrO 2 -HfO 2 . An alkaline fusion to open the mineral, followed by a purification by crystallization as (Zr O-Hf O)Cl 2 H 2 O or as (Zr-Hf) (SO 4 ) 2 . 4H 2 O, is used. A discussion of the best experimental conditions for opening the mineral and of the purification method is made. (Author) 45 refs

Effects of therapy with [177Lu-DOTA0,Tyr3]octreotate on endocrine function

International Nuclear Information System (INIS)

Teunissen, Jaap J.M.; Kwekkeboom, Dik J.; Krenning, Eric P.; Jong, Frank H. de; Feelders, Richard A.; Aken, Maarten O. van; Herder, Wouter W. de; Rijke, Yolanda B. de

2009-01-01

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 ± 16 to 25 ± 4 ng/l, p 4 ) levels decreased (17.7 ± 0.4 to 15.6 ± 0.6 pmol/l, p 3 ) levels did not change. Reverse triiodothyronine (rT 3 ) levels decreased (0.38 ± 0.03 to 0.30 ± 0.01 nmol/l, p 550 nmol/l, n = 18). Five patients developed elevated HbA 1c levels (> 6.5%). In men 177 Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non-SHBG-bound T levels remained unaffected. In the long term, gonadotropin levels decreased significantly in postmenopausal women. Only a few patients developed hypothyroidism or elevated levels of HbA 1c . Therefore, PRRT with 177 Lu-octreotate can be regarded as a safe treatment modality with respect to short- and long-term endocrine function. (orig.)

Tumoral fibrosis effect on the radiation absorbed dose of 177Lu–Tyr3-octreotate and 177Lu–Tyr3-octreotate conjugated to gold nanoparticles

International Nuclear Information System (INIS)

Azorín-Vega, E.P.; Zambrano-Ramírez, O.D.; Rojas-Calderón, E.L.; Ocampo-García, B.E.; Ferro-Flores, G.

2015-01-01

The aim of this work was to evaluate the tumoral fibrosis effect on the radiation absorbed dose of the radiopharmaceuticals 177 Lu–Tyr 3 -octreotate (monomeric) and 177 Lu–Tyr 3 -octreotate–gold nanoparticles (multimeric) using an experimental HeLa cells tumoral model and the Monte Carlo PENELOPE code. Experimental and computer micro-environment models with or without fibrosis were constructed. Results showed that fibrosis increases up to 33% the tumor radiation absorbed dose, although the major effect on the dose was produced by the type of radiopharmaceutical (112 Gy-multimeric vs. 43 Gy-monomeric). - Highlights: • Fibrosis increases the radiation absorbed dose to the tumor. • Fibrosis increases the radiopharmaceutical residence time in the tumor. • The multimeric nature of the radiopharmaceuticals enhances the radiopharmaceutical retention

Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors: First comparative results using the somatostatin analogues Lu-177 DOTA-NOC and Lu-177 DOTA-TATE

International Nuclear Information System (INIS)

Wehrmann, C.; Senftleben, S.; Baum, R.P.

2005-01-01

Peptide receptor radionuclide therapy (PRRT) is used in our department since 5 years (approx. 400 applications) for the treatment of patients with metastatic neuroendocrine tumors. Of all known peptides, the somatostatin analogue DOTA-NOC shows in vitro the highest affinity to somatostatin receptors (sstr) 3 and 5 and a very high affinity to sstr 2. We studied the in vivo behaviour of the two peptides DOTA-NOC and DOTA-TATE (highest affinity to sstr 2) by the use of different parameters like tumor and organ uptake, effective half-lifes (kinetics) and mean absorbed organ and tumor doses. We studied 27 patients with metastatic neuroendocrine tumors with high somatostatin expression, as verified prior to treatment by Ga-68 DOTA-NOC receptor PET/CT or somatostatin receptor scintigraphy (Tc-99m EDDA-Hynic TOC or In-111 OctreoScan, planar and SPECT). 22 patients (8M and 14F; aged 619 years) were treated with 2500 6790 MBq Lu-177 DOTA-TATE. Another 5 patients (1M and 4F, aged 6310 years) were treated with 4000 7400 MBq Lu-177 DOTA-NOC. Labelling efficiency and radiochemical purity using Lutetium-177 chloride (obtained from PerkinElmer Life Sciences, USA) were constantly over 99.5%. Whole-body scans (anterior/posterior) were performed at 0.5h, 3h, 24h, 48h, 72h and 96h p.i. ROIs were drawn over the whole-body, organs, and different metastases (mainly in the liver). Blood samples were obtained in 12 patients after therapy with Lu-177 DOTA-TATE over 5 days for calculating the kinetics in blood. The ROI results were used to determine the uptake and effective half-life in different organs (kidney, spleen, liver, bone etc.) and the tumor residence times. By means of geometric mean, and after background correction, the ROI results were also used to calculate the estimated absorbed organ and tumor doses using the OLINDA software. Compared to Lu-177 DOTA-TATE (=100%), the uptake of Lu-177 DOTA-NOC was higher for the whole-body (45%) and for normal tissues (28%), and also in the

CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera

Directory of Open Access Journals (Sweden)

Bettinotti Maria

2004-03-01

Full Text Available Abstract Genes in the Leukocyte Antigen 6 (Ly-6 superfamily encode glycosyl-phosphatidylinositol (GPI anchored glycoproteins (gp with conserved domains of 70 to 100 amino acids and 8 to 10 cysteine residues. Murine Ly-6 genes encode important lymphocyte and hematopoietic stem cell antigens. Recently, a new member of the human Ly-6 gene superfamily has been described, CD177. CD177 is polymorphic and has at least two alleles, PRV-1 and NB1. CD177 was first described as PRV-1, a gene that is overexpressed in neutrophils from approximately 95% of patients with polycythemia vera and from about half of patients with essential thrombocythemia. CD177 encodes NB1 gp, a 58–64 kD GPI gp that is expressed by neutrophils and neutrophil precursors. NB1 gp carries Human Neutrophil Antigen (HNA-2a. Investigators working to identify the gene encoding NB1 gp called the CD177 allele they described NB1. NB1 gp is unusual in that neutrophils from some healthy people lack the NB1 gp completely and in most people NB1 gp is expressed by a subpopulation of neutrophils. The function of NB1 gp and the role of CD177 in the pathogenesis and clinical course of polycythemia vera and essential thrombocythemia are not yet known. However, measuring neutrophil CD177 mRNA levels has become an important marker for diagnosing the myeloproliferative disorders polycythemia vera and essential thrombocythemia.

Third-line treatment and {sup 177}Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

Energy Technology Data Exchange (ETDEWEB)

Edler von Eyben, Finn [Center of Tobacco Control Research, Odense (Denmark); Roviello, Giandomenico [San Donato Hospital, Department of Oncology, Medical Oncology Unit, Arezzo (Italy); University of Trieste, Department Medical, Surgery, and Health Sciences, Trieste (Italy); Kiljunen, Timo; Kairemo, Kalevi; Joensuu, Timo [Docrates Cancer Center, Helsinki (Finland); Uprimny, Christian; Virgolini, Irene [University Hospital Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

2018-03-15

There is a controversy as to the relative efficacy of {sup 177}Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether {sup 177}Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. Twelve studies including 669 patients reported {sup 177}Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with {sup 177}Lu-PSMA RLT. The treatment with {sup 177}Lu-PSMA-617 and {sup 177}Lu-PSMA for imaging and therapy (I and T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. {sup 177}Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). {sup 177}Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ{sup 2} test). Median survival was longer after {sup 177}Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for {sup 177}Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ{sup 2

21 CFR 177.1635 - Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene).

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Poly(p-methylstyrene) and rubber-modified poly(p-methyl-styrene). 177.1635 Section 177.1635 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components...

George de Hevesy (1885-1966). Discoverer of hafnium, founder of radioanalytical chemistry and X-ray fluorescence analysis and father of nuclear medicine

International Nuclear Information System (INIS)

Niese, Siegfried

2017-01-01

George de Hevesy known as discoverer of hafnium, founder of radioanalytical chemistry and X-ray fluorescence analysis and father of nuclear medicine has done important research work in inorganic, physical and radioanalytical and physiological chemistry as well as in geochemistry, radiation biology and medicine. When he must flee for political reasons from a country he must change his colleagues, his equipments, and the topic of his work. It is extremely surprising that he could receive important results under such circumstances even at an advanced age. (author)

Internal radiotherapy and dosimetric study for 111In/177Lu-pegylated liposomes conjugates in tumor-bearing mice

International Nuclear Information System (INIS)

Wang, H.-E.; Yu, H.-M.; Lu, Y.-C.; Heish, N.-N.; Tseng, Yun-Long; Huang, K.-L.; Chuang, K.-T.; Chen, Chin-Hsiung; Hwang, J.-J.; Lin, W.-J.; Wang, Shyh-Jen; Ting, G.; Whang-Peng, Jacqueline; Deng, W.-P.

2006-01-01

In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with 111 In/ 177 Lu-(oxine) 3 to afford 111 In/ 177 Lu-liposome. The stability of 111 In/ 177 Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of 111 In/ 177 Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of 111 In/ 177 Lu into liposomes was 95%. After incubation at 37 o C for 72 h in serum, more than 83% of radioactivity was still retained in the intact 111 In/ 177 Lu-liposomes. The biodistribution of 111 In-liposomes showed that the radioactivity in the blood decreased from 23.14±8.16%ID/g at 1 h to 0.02±0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of 177 Lu-liposomes. Scintigraphic imaging with 111 In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from 177 Lu-liposomes was 5.74x10 -5 Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes

Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate

NARCIS (Netherlands)

van Vliet, Esther I.; van Eijck, Casper H.; de Krijger, Ronald R.; Nieveen van Dijkum, Elisabeth J.; Teunissen, Jaap J.; Kam, Boen L.; de Herder, Wouter W.; Feelders, Richard A.; Bonsing, Bert A.; Brabander, Tessa; Krenning, Eric P.; Kwekkeboom, Dik J.

2015-01-01

Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) may be an option. We

21 CFR 177.1400 - Hydroxyethyl cellulose film, water-insoluble.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Hydroxyethyl cellulose film, water-insoluble. 177... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances... packaging food in accordance with the following prescribed conditions: (a) Water-insoluble hydroxyethyl...

Silicon-doped hafnium oxide anti-ferroelectric thin films for energy storage

Science.gov (United States)

Ali, Faizan; Liu, Xiaohua; Zhou, Dayu; Yang, Xirui; Xu, Jin; Schenk, Tony; Müller, Johannes; Schroeder, Uwe; Cao, Fei; Dong, Xianlin

2017-10-01

Motivated by the development of ultracompact electronic devices as miniaturized energy autonomous systems, great research efforts have been expended in recent years to develop various types of nano-structural energy storage components. The electrostatic capacitors characterized by high power density are competitive; however, their implementation in practical devices is limited by the low intrinsic energy storage density (ESD) of linear dielectrics like Al2O3. In this work, a detailed experimental investigation of energy storage properties is presented for 10 nm thick silicon-doped hafnium oxide anti-ferroelectric thin films. Owing to high field induced polarization and slim double hysteresis, an extremely large ESD value of 61.2 J/cm3 is achieved at 4.5 MV/cm with a high efficiency of ˜65%. In addition, the ESD and the efficiency exhibit robust thermal stability in 210-400 K temperature range and an excellent endurance up to 109 times of charge/discharge cycling at a very high electric field of 4.0 MV/cm. The superior energy storage performance together with mature technology of integration into 3-D arrays suggests great promise for this recently discovered anti-ferroelectric material to replace the currently adopted Al2O3 in fabrication of nano-structural supercapacitors.

Tuning the magnetic properties of pure hafnium by high pressure torsion

International Nuclear Information System (INIS)

Cepeda-Jiménez, C.M.; Beltrán, J.I.; Hernando, A.; García, M.A.; Ynduráin, F.; Zhilyaev, A.; Pérez-Prado, M.T.

2017-01-01

This work demonstrates that room temperature (RT) ferromagnetism might be triggered in pure hafnium (Hf), a classic paramagnet, by severe plastic deformation (SPD) via high pressure torsion (HPT). The origin of this phenomenon is elucidated by a combined approach including density functional theory (DFT) calculations and transmission electron microscopy (TEM). In particular, it is shown that the elastic lattice distorsions induced in pure Hf as a consequence of grain refinement down to the nanocrystalline regime by HPT lead to the development of a new monoclinic crystalline structure that exhibits a spontaneous magnetization at RT. DFT calculations are utilized to prove that local stretching of the original pure Hf hexagonal close packed (hcp) lattice along specific pyramidal directions, due to the presence of internal stresses in the deformed nanostructure, may give rise to the emergence of the monoclinic phase, which is endowed with a net magnetic moment. An excellent agreement is found between DFT calculations and experimental TEM observations, which provide a first evidence of the presence of the pure Hf monoclinic crystal lattice. This work shows that SPD may constitute a viable, yet widely unexplored, strategy to tune the magnetic properties and, in particular, to induce RT ferromagnetism in bulk non-magnetic metals.

[177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

Science.gov (United States)

Baum, Richard P.; Kluge, Andreas W.; Kulkarni, Harshad; Schorr-Neufing, Ulrike; Niepsch, Karin; Bitterlich, Norman; van Echteld, Cees J.A.

2016-01-01

Purpose: To characterise efficacy and safety of 177Lu-DOTATOC as agent for peptide receptor radiotherapy (PRRT) of advanced neuroendocrine tumours (NET). Patients and methods: Fifty-six subjects with metastasized and progressive NET (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites) treated consecutively with 177Lu-DOTATOC were analysed retrospectively. Subjects were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) as 7.0GBq (median) doses at three-monthly intervals. Efficacy was analysed using CT and/or MRI according to RECIST 1.1 criteria and results were stratified for the number of administered cycles and the primary tumour origin. Results: In the total NET population (A), median progression-free (PFS) and overall survival (OS) were 17.4 and 34.2 months, respectively, assessed in a follow-up time (mean ± SD) of 16.1 ± 12.4 months. In patients receiving more than one cycle, mean follow-up time was 22.4 ± 11.0 months for all NETs (B) and PFS was 32.0 months for all NETs (B), 34.5 months for GEP-NET (C), and 11.9 months for other NETs (D). Objective response rates (Complete/Partial Responses) were 33.9%, 40.6%, 54.2%, and 0% for A, B, C, and D groups, respectively, while disease control rates in the same were 66.1%, 93.8%, 100%, and 75%. Complete responses (16.1%, 18.8% and 25.0% for groups A, B and C) were high, 78% of which were maintained throughout the follow up. There were no serious adverse events. One case of self-limiting grade 3 myelotoxicity was reported. Although 20% of patients had mild renal insufficiency at baseline, there was no evidence of exacerbated or de novo renal toxicity after treatment. Conclusion: 177Lu-DOTATOC is a novel agent for PRRT with major potential to induce objective tumour responses and sustained disease control in progressive neuroendocrine tumours, even when administered in moderate activities. The observed safety profile suggests a particularly favourable therapeutic index, including in patients with

Toxicity of trastuzumab labeled {sup 177}Lu on MCF7 and SKBr3 cell lines

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); Hossein Babaei, Mohammad; Johari Daha, Fariba [Department of Radioisotope, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of)

2010-10-15

In this study, we labeled trastuzumab with {sup 177}Lu to synthesize a new radiopharmaceutical for therapy of breast cancer and at the first stage investigated its therapeutic effects on SKBr3 and MCF7 breast cancer cell lines. Trastuzumab-{sup 177}Lu showed very good in-vitro characteristics such as high radiochemical purity (91{+-}0.9%), good stability in PBS buffer (86{+-}2.3%) and blood serum (81{+-}2.7%) up to 96 h, appropriate immunoreactivity (85.4{+-}1.1%) and high cytotoxicity in HER2 expression cells. 5 fold increase in toxicity of trastuzumab-{sup 177}Lu was observed when compared with unlabeled trastuzumab on SKBr3 cells.

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

Characterization of hafnium oxide resistive memory layers deposited on copper by atomic layer deposition

Energy Technology Data Exchange (ETDEWEB)

Briggs, B.D.; Bishop, S.M. [SUNY College of Nanoscale Science and Engineering, 255 Fuller Road, Albany, NY 12203 (United States); Leedy, K.D. [Air Force Research Laboratory, 2241 Avionics Circle, Wright Patterson Air Force Base, Dayton, OH 45433 (United States); Cady, N.C., E-mail: ncady@albany.edu [SUNY College of Nanoscale Science and Engineering, 255 Fuller Road, Albany, NY 12203 (United States)

2014-07-01

Hafnium oxide-based resistive memory devices have been fabricated on copper bottom electrodes. The HfO{sub x} active layers in these devices were deposited by atomic layer deposition (ALD) at 250 °C with tetrakis(dimethylamido)hafnium(IV) as the metal precursor and an O{sub 2} plasma as the reactant. Depth profiles of the HfO{sub x} by X-ray photoelectron spectroscopy and secondary ion mass spectroscopy revealed a copper concentration on the order of five atomic percent throughout the HfO{sub x} film. In addition to the Cu doped HfO{sub x}, a thin layer (20 nm) of Cu{sub x}O is present at the surface. This surface layer is believed to have formed during the ALD process, and greatly complicates the analysis of the switching mechanism. The resistive memory structures fabricated from the ALD HfO{sub x} exhibited non-polar resistive switching, independent of the top metal electrode (Ni, Pt, Al, Au). Resistive switching current voltage (I–V) curves were analyzed using Schottky emission and ionic hopping models to gain insight into the physical mechanisms underpinning the device behavior. During the forming process it was determined that, at voltages in excess of 2.5 V, an ionic hopping model is in good agreement with the I–V data. The extracted ion hopping distance ∼ 4 Å was within the range of interatomic spacing of HfO{sub 2} during the forming process consistent with ionic motion of Cu{sup 2+} ions. Lastly the on state I–V data was dominated at larger voltages by Schottky emission with an estimated barrier height of ∼ 0.5 eV and a refractive index of 2.59. The consequence of the Schottky emission analysis indicates the on state resistance to be a product of a Pt/Cu{sub 2}O/Cu filament(s)/Cu{sub 2}O/Cu structure. - Highlights: • HfO{sub 2} was grown via atomic layer deposition at 250 and 100 °C on Cu substrates. • A Cu{sub 2}O surface layer and Cu doping were observed in post-deposition of HfO{sub 2}. • Resistive memory devices were fabricated and

Thermodynamic and kinetic studies in the systems alkali chloride-zinconium (or hafnium) tetrachloride: Part I. Vapour pressure measurements over hexachloro compounds and use of vapour pressure data in fractional decomposition

International Nuclear Information System (INIS)

Ray, H.S.; Bhat, B.G.; Reddy, G.S.; Biswas, A.K.

1978-01-01

A molten tin isoteniscope has been used to measure the vapour pressures over ZrCl 4 , HfCl 4 and the hexachlore zirconates (M 2 ZrCl 6 ) and the hexachloro hafnates (M 2 HfCl 6 ) of four alkali metals (M = Na,K,Rb,Cs). The method of preparation of these compounds and the effect of small amounts of residual alkali chlorides on the their vapour pressure are discussed. The pressure-temperature plots are examined in the light of some theoretical postulates. A scheme for separation of hafnium from zirconoium by multistage fractional decomposition of the hexachlore compounds of any alkali metal is described. The scheme, which is analogous to rectification in liquid-vapour systems, employs a countercurrent flow of Zr(Hf)Cl 4 in a gas stream and a moving bed of alkali chlorides. The separation is based on the difference in the dissociation equilibrium for zirconium and hafnium compounds. Stage calculations for such a scheme and the main conclusions of a computational work are presented. (author)

Evaluation of the therapeutic efficacy and radiotoxicity of the conjugates 177Lu-DOTA-E-c(RGDfK)2 and 177Lu-DOTA-GGC-AuNP-c[RGDfk(C)] in a murine model and their relationship with the inhibition of the angiogenic factors VEGF and HIF-1α

International Nuclear Information System (INIS)

Vilchis J, A.

2013-01-01

Molecular targeting therapy has become a relevant therapeutic strategy for cancer. The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been proven, and radiolabeled peptides have been demonstrated to be effective in patients with malignant tumors. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of α(v)β(3) integrin, thereby inhibiting angio genesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable m ultimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of 177 Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare with that of 177 Lu-AuNP or 177 Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-micro PET/CT), renal radiotoxicity, renal and tumoral histological characteristics as well as tumoral VEGF and HIF-1? gene expression (by realtime polymerase chain reaction) following treatment with 177 Lu-AuNP-RGD, 177 Lu-AuNP or 177 Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, 177 Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 ± 7.9 Gy) vs other treatments. These results correlated with the observed therapeutic response, in which 177 Lu-AuNP-RGD significantly (p 177 Lu). There was a low uptake in non-target organs and no induction of renal toxicity. 177 Lu-AuNP-RGD demonstrates properties suitable for use as an agent for molecular targeting radiotherapy. (Author)

Radiosynthesis and preclinical studies of 177Lu-labeled sulfadiazine. A possible theranostic agent for deep-seated bacterial infection

International Nuclear Information System (INIS)

Syed Ali Raza Naqvi; Rashid Rasheed; Muhammad Tauqeer Ahmed; Ameer Fawad Zahoor

2017-01-01

Sulfadiazine acts through inhibition of bacterial dihydropteroate synthetase. The radio-labeling of sulfadiazine with lutetium-177 ( 177 Lu) is expected to serve as a theranostic agent for deep-seated bacterial infections. The radiosynthesis of 177 Lu-sulfadiazine indicated a > 95% yield under optimized reaction conditions, and promising stability was found in blood serum. Biodistribution data in the absence of infection revealed minimal accumulation in key body organs. Kidneys were the main excretory organs, showed an uptake of 1.76 ± 0.09% ID/g organ at 6-h post-injection. Biodistribution, scintigraphic data, glomerular filtration rate, and cytotoxicity results encourage clinical investigation of 177 Lu-sulfadiazine as a novel theranostic agent for deep-seated bacterial infection. (author)

28 CFR 0.177 - Applications for orders under the Comprehensive Drug Abuse Prevention and Control Act.

Science.gov (United States)

2010-07-01

... Comprehensive Drug Abuse Prevention and Control Act. 0.177 Section 0.177 Judicial Administration DEPARTMENT OF... the Comprehensive Drug Abuse Prevention and Control Act. Notwithstanding the delegation of functions... authorized to exercise the authority vested in the Attorney General by section 514 of the Comprehensive Drug...

177Lu-DTPA-BIS-BIOTIN Binding of Octreotide-dextran-avidinated PANC-1 Cell Lines in Vitro

International Nuclear Information System (INIS)

Deng Xinrong; Zhai Shizhen; Shen Yijia; Luo Zhifu; Du Jin

2011-01-01

Tyr3-octreotide, dextran-40 and avidin were used to prepare octreotide-dextran-avidin (TOC-Dx 40 -Av). DTPA-BIS-BIOTIN was labelled with 177 Lu. The in vitro somatostatin receptor binding study was carried out by pretargeted method using TOC-Dx 40 -Av and 177 Lu-DTPA-BIS-BIOTIN. The 24 well cell culture plates were prepared with PANC-1 cell monolayer and then incubated with TOC-Dx 40 -Av. After two washed with PBS, the cells were incubated with different concentration of 177 Lu-DTPA-BIS-BIOTIN (48.8 ∼ 391 pmol). Cells uptake was evaluated with γ counter. The results showed that the chemical purity of TOC-Dx 40 -Av was over 99%. The results also showed that TOC-Dx 40 -Av remained high receptor binding affinity to somatostatin receptor which indicated that TOC- Dx 40 -Av could bind to 177 Lu-DTPA-BIS-BIOTIN with the molar ratio of 1 : 1 on the cell surface. (authors)

14 CFR 406.177 - Petition to reconsider or modify a final decision and order of the FAA decisionmaker on appeal.

Science.gov (United States)

2010-01-01

... decision and order of the FAA decisionmaker on appeal. 406.177 Section 406.177 Aeronautics and Space... INVESTIGATIONS, ENFORCEMENT, AND ADMINISTRATIVE REVIEW Rules of Practice in FAA Space Transportation Adjudications § 406.177 Petition to reconsider or modify a final decision and order of the FAA decisionmaker on...

Production and Stability Study of High Activity 177Lu-Substance P as a Radiopharmaceutical for Malignant Tumors Treatment

International Nuclear Information System (INIS)

Araujo, E.B. de; Lima, C.M. de; Pujatti, P.B.; Mengatti, J.

2009-01-01

In recent years, a high number of new developments in target therapies have emerged and the presence of peptide receptors and transporters at the cell membrane of several tumors constitutes the basis of the clinical use of specific radiolabeled ligands, such as Substance P (SP). SP is an 11-amino acid neuropeptide member of the family of tachykinins, characterized by the C-terminal sequence Phe-X- Gly-Leu-Met-NH 2 . It has been well established that SP plays an important role in modulating pain transmission from peripheral and central primary afferents and this peptide may be also involved in the pathogenesis of inflammatory diseases. SP receptors are also found in brain, lymphoid tissues, vessels, gut smooth muscle, airway glands and bronchiolar walls. In receptor autoradiography of tumor specimens ex vivo, SP receptors were found on glioblastoma, medullary thyroid cancer, non- small cell lung cancer and carcinoma of pancreas, but the incidence is low in the last two. The introduction of radiolabeled SP for peptide receptor radiotherapy can be an alternative to treat these tumors by radionuclide therapy or loco-regional instillation. Several radioisotopes have been applied to radiolabel peptides for radionuclide therapy and 6.7 day half-life 177 Lu has emerged as a promising β- emitter for this purpose. The energy (497 keV) and mean range (670 μm) of lutetium-177 β particles are ideal for small tumors and micro-metastatic disease treatment. Because it also emits γ rays (208 keV, 11% abundance), imaging of 177 Lu-labeled endoradiotherapeutic agents is also possible. The goal of the present work was to determine the best radiolabeling conditions and the stability of SP complexed to DOTA chelator, using 177 Lu as radionuclide. The optimized condition was applied to produce a high activity and stable 177Lu-DOTA-SP, as a radiopharmaceutical for malignant tumors treatment. Substance P was radiolabeled at different conditions in order to determine the best

Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

International Nuclear Information System (INIS)

Hassan Yousefnia; Amir Reza Jalilian; Ali Bahrami-Samani; Simindokht Shirvani-Arani; Mohammad Ghannadi-Maragheh; Azim Arbabi; Edalat Radfar

2011-01-01

Rituximab was successively labeled with 177 Lu-lutetium chloride. 177 Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm -2 s -1 ) of natural Lu 2 O 3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA, N-hydroxy succinimide (NHS) in CH 2 Cl 2 . DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 deg C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 deg C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177 Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported. (author)

Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer 177Lu-AMBA

International Nuclear Information System (INIS)

Waser, Beatrice; Eltschinger, Veronique; Reubi, Jean C.; Linder, Karen; Nunn, Adrian

2007-01-01

To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, 177 Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3. In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand 177 Lu-AMBA was used and compared with established bombesin radioligands such as 125 I-Tyr 4 -bombesin and 125 I-[D-Tyr 6 ,β-Ala 11 ,Phe 13 ,Nle 14 ]-bombesin(6-14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. 177 Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. 177 Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with 177 Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with 177 Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with 177 Lu-AMBA than with the conventional bombesin radioligands. The present in vitro study suggests that 177 Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessels. (orig.)

Somatostatin-based radiopeptide therapy with [{sup 177}Lu-DOTA]-TOC versus [{sup 90}Y-DOTA]-TOC in neuroendocrine tumours

Energy Technology Data Exchange (ETDEWEB)

Romer, A.; Seiler, D.; Brunner, P.; Ng, Q.K.T.; Mueller-Brand, J. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Marincek, N.; Walter, M.A. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); Koller, M.T. [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); Maecke, H.R. [University Hospital Basel, Division of Radiochemistry, Basel (Switzerland); Rochlitz, C. [University Hospital Basel, Department of Oncology, Basel (Switzerland); Briel, M. [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton (Canada); Schindler, C. [University of Basel, Swiss Tropical and Public Health Institute, Basel (Switzerland)

2014-02-15

Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides {sup 90}Y or {sup 177}Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [{sup 90}Y-DOTA]-TOC or [{sup 177}Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [{sup 90}Y-DOTA]-TOC and 141 patients underwent 259 cycles of [{sup 177}Lu-DOTA]-TOC. The median survival after [{sup 177}Lu-DOTA]-TOC and after [{sup 90}Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [{sup 177}Lu-DOTA]-TOC over [{sup 90}Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [{sup 177}Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [{sup 177}Lu-DOTA]-TOC and [{sup 90}Y-DOTA]-TOC. Furthermore, [{sup 177}Lu-DOTA]-TOC was less haematotoxic than [{sup 90}Y-DOTA]-TOC. (orig.)

Development of 177Lu-phytate Complex for Radiosynovectomy

Directory of Open Access Journals (Sweden)

Hassan Yousefnia

2013-05-01

Full Text Available Objective(s: In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation. Materials and Methods: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 n.cm-2.s-1. The product was converted into chloride form which was further used for labeling of 177Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase. The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 µCi/100 µl was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days. Results: The complex was successfully prepared with high radiochemical purity (>99.9 %. Approximately, the whole injected dose has remained in injection site seven days after injection. Conclusion: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology

Metallorganic chemical vapor deposition and atomic layer deposition approaches for the growth of hafnium-based thin films from dialkylamide precursors for advanced CMOS gate stack applications

Science.gov (United States)

Consiglio, Steven P.

To continue the rapid progress of the semiconductor industry as described by Moore's Law, the feasibility of new material systems for front end of the line (FEOL) process technologies needs to be investigated, since the currently employed polysilicon/SiO2-based transistor system is reaching its fundamental scaling limits. Revolutionary breakthroughs in complementary-metal-oxide-semiconductor (CMOS) technology were recently announced by Intel Corporation and International Business Machines Corporation (IBM), with both organizations revealing significant progress in the implementation of hafnium-based high-k dielectrics along with metal gates. This announcement was heralded by Gordon Moore as "...the biggest change in transistor technology since the introduction of polysilicon gate MOS transistors in the late 1960s." Accordingly, the study described herein focuses on the growth of Hf-based dielectrics and Hf-based metal gates using chemical vapor-based deposition methods, specifically metallorganic chemical vapor deposition (MOCVD) and atomic layer deposition (ALD). A family of Hf source complexes that has received much attention recently due to their desirable properties for implementation in wafer scale manufacturing is the Hf dialkylamide precursors. These precursors are room temperature liquids and possess sufficient volatility and desirable decomposition characteristics for both MOCVD and ALD processing. Another benefit of using these sources is the existence of chemically compatible Si dialkylamide sources as co-precursors for use in Hf silicate growth. The first part of this study investigates properties of MOCVD-deposited HfO2 and HfSixOy using dimethylamido Hf and Si precursor sources using a customized MOCVD reactor. The second part of this study involves a study of wet and dry surface pre-treatments for ALD growth of HfO2 using tetrakis(ethylmethylamido)hafnium in a wafer scale manufacturing environment. The third part of this study is an investigation of

Recoil Induced Room Temperature Stable Frenkel Pairs in a-Hafnium Upon Thermal Neutron Capture

Science.gov (United States)

Butz, Tilman; Das, Satyendra K.; Dey, Chandi C.; Ghoshal, Shamik

2013-11-01

Ultrapure hafnium metal (110 ppm zirconium) was neutron activated with a thermal neutron flux of 6:6 · 1012 cm-2s-1 in order to obtain 181Hf for subsequent time differential perturbed angular correlation (TDPAC) experiments using the nuclear probe 181Hf(β-) 181Ta. Apart from the expected nuclear quadrupole interaction (NQI) signal for a hexagonal close-packed (hcp) metal, three further discrete NQIs were observed with a few percent fraction each. The TDPAC spectra were recorded for up to 11 half lives with extreme statistical accuracy. The fitted parameters vary slightly within the temperature range between 248 K and 373 K. The signals corresponding to the three additional sites completely disappear after `annealing' at 453 K for one minute. Based on the symmetry of the additional NQIs and their temperature dependencies, they are tentatively attributed to Frenkel pairs produced by recoil due to the emission of a prompt 5:694 MeV -ray following thermal neutron capture and reported by the nuclear probe in three different positions. These Frenkel pairs are stable up to at least 373 K.

177Lu-labeled HPMA copolymers utilizing cathepsin B and S cleavable linkers: Synthesis, characterization and preliminary in vivo investigation in a pancreatic cancer model

International Nuclear Information System (INIS)

Ogbomo, Sunny M.; Shi, Wen; Wagh, Nilesh K.; Zhou, Zhengyuan; Brusnahan, Susan K.; Garrison, Jered C.

2013-01-01

Introduction: A major barrier to the advancement of therapeutic nanomedicines has been the non-target toxicity caused by the accumulation of the drug delivery systems in organs associated with the reticuloendothelial system, particularly the liver and spleen. Herein, we report the development of peptide based metabolically active linkers (MALs) that are enzymatically cleaved by cysteine cathepsin B and S, two proteases highly expressed in the liver and spleen. The overall goal of this approach is to utilize the MALs to lower the non-target retention and toxicity of radiolabeled drug delivery systems, thus resulting in higher diagnostic and radiotherapeutic efficacy. Methods: In this study three MALs (MAL0, MAL1 and MAL2) were investigated. MAL1 and MAL2 are composed of known substrates of cathepsin B and S, respectively, while MAL0 is a non-cleavable control. Both MAL1 and MAL2 were shown to undergo enzymatic cleavage with the appropriate cathepsin protease. Subsequent to conjugation to the HPMA copolymer and radiolabeling with 177 Lu, the peptide–polymer conjugates were renamed 177 Lu-metabolically active copolymers ( 177 Lu-MACs) with the corresponding designations: 177 Lu-MAC0, 177 Lu-MAC1 and 177 Lu-MAC2. Results: In vivo evaluation of the 177 Lu-MACs was performed in an HPAC human pancreatic cancer xenograft mouse model. 177 Lu-MAC1 and 177 Lu-MAC2 demonstrated 3.1 and 2.1 fold lower liver retention, respectively, compared to control ( 177 Lu-MAC0) at 72 h post-injection. With regard to spleen retention, 177 Lu-MAC1 and 177 Lu-MAC2 each exhibited a nearly fourfold lower retention, relative to control, at the 72 h time point. However, the tumor accumulation of the 177 Lu-MAC0 was two to three times greater than 177 Lu-MAC1 and 177 Lu-MAC2 at the same time point. The MAL approach demonstrated the capability of substantially reducing the non-target retention of the 177 Lu-labeled HPMA copolymers. Conclusions: While further studies are needed to optimize the

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate

Directory of Open Access Journals (Sweden)

Dale Bailey

2016-01-01

Full Text Available Objective(s:Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as “No Carrier Added” (NCA 177Lu. We have radiolabelled DOTA-conjugated peptide DOTA‐(Tyr3‐octreotate with NCA 177Lu (“NCA-LuTATE” and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body (WB and quantitative 3D SPECT (qSPECT 177Lu imaging. Methods: Thirteen patients received 39 NCA-LuTATE injections. Extensive WB planar and qSPECT imaging was acquired at approximately 0.5, 4, 24 and 96 h to permit estimates of clearance and radiation dose estimation using MIRD-based methodology (OLINDA-EXM. Results:The average amount of NCA-Lutate administered per cycle was 7839±520 MBq. Bi-exponential modelling of whole body clearance showed half lives for the fast & slow components of t½=2.1±0.6 h and t½=58.1±6.6 h respectively. The average effective dose to kidneys was 3.1±1.0 Gy per cycle. In eight patients completing all treatment cycles the average total dose to kidneys was 11.7±3.6 Gy. Conclusions: We have shown that NCA-LuTATE has an acceptable radiation safety profile and is a suitable alternative to Carrier-Added 177Lu formulations. The fast component of the radiopharmaceutical clearance was closely correlated with baseline renal glomerular filtration rate, and this had an impact on radiation dose to the kidneys. In addition, it has less radioactive waste issues and requires less peptide per treatment.

Evaluation of the therapeutic efficacy and radiotoxicity of the conjugates {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} and {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfk(C)] in a murine model and their relationship with the inhibition of the angiogenic factors VEGF and HIF-1α; Evaluacion de la eficacia terapeutica y radiotoxicidad de los conjugados {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} y {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfK(C)] en un modelo murino y su relacion con la inhibicion de los factores angiogenicos VEGF y HIF-1α

Energy Technology Data Exchange (ETDEWEB)

Vilchis J, A.

2013-07-01

Molecular targeting therapy has become a relevant therapeutic strategy for cancer. The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been proven, and radiolabeled peptides have been demonstrated to be effective in patients with malignant tumors. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of α(v)β(3) integrin, thereby inhibiting angio genesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable m ultimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of {sup 177}Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare with that of {sup 177}Lu-AuNP or {sup 177}Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-micro PET/CT), renal radiotoxicity, renal and tumoral histological characteristics as well as tumoral VEGF and HIF-1? gene expression (by realtime polymerase chain reaction) following treatment with {sup 177}Lu-AuNP-RGD, {sup 177}Lu-AuNP or {sup 177}Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, {sup 177}Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 ± 7.9 Gy) vs other treatments. These results correlated with the observed therapeutic response, in which {sup 177}Lu-AuNP-RGD significantly (p<0.05) reduced tumor progression, tumor metabolic activity, intratumoral vessels and VEGF gene expression compared to the other radiopharmaceuticals. This was consequence of high tumor retention and a combination of molecular targeting therapy (m ultimeric RGD system) and radiotherapy ({sup 177}Lu). There was a low uptake in non-target organs and no induction of renal toxicity. {sup 177}Lu-AuNP-RGD demonstrates properties suitable for use as an agent for molecular targeting radiotherapy. (Author)

The energy landscape of glassy dynamics on the amorphous hafnium diboride surface

Science.gov (United States)

Nguyen, Duc; Mallek, Justin; Cloud, Andrew N.; Abelson, John R.; Girolami, Gregory S.; Lyding, Joseph; Gruebele, Martin

2014-11-01

Direct visualization of the dynamics of structural glasses and amorphous solids on the sub-nanometer scale provides rich information unavailable from bulk or conventional single molecule techniques. We study the surface of hafnium diboride, a conductive ultrahigh temperature ceramic material that can be grown in amorphous films. Our scanning tunneling movies have a second-to-hour dynamic range and single-point current measurements extend that to the millisecond-to-minute time scale. On the a-HfB2 glass surface, two-state hopping of 1-2 nm diameter cooperatively rearranging regions or "clusters" occurs from sub-milliseconds to hours. We characterize individual clusters in detail through high-resolution (single cluster vertical displacements, we can reconstruct the local free energy landscape of individual clusters, complete with activation barrier height, a reaction coordinate in nanometers, and the shape of the free energy landscape basins between which hopping occurs. The experimental images are consistent with the compact shape of α-relaxors predicted by random first order transition theory, whereas the rapid hopping rate, even taking less confined motion at the surface into account, is consistent with β-relaxations. We make a proposal of how "mixed" features can show up in surface dynamics of glasses.

49 CFR 17.7 - How does the Secretary communicate with state and local officials concerning the Department's...

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false How does the Secretary communicate with state and local officials concerning the Department's programs and activities? 17.7 Section 17.7 Transportation Office of the Secretary of Transportation INTERGOVERNMENTAL REVIEW OF DEPARTMENT OF TRANSPORTATION...

About the structure and stability of complex carbonates of thorium (IV), cerium (IV), zirconium (IV), hafnium (IV)

International Nuclear Information System (INIS)

Dervin, Jacqueline

1972-01-01

This research thesis addressed the study of complex carbonates of cations of metals belonging to the IV A column, i.e. thorium (IV), zirconium (IV), hafnium (IV), and also cerium (IV) and uranium (VI), and more particularly focused on ionic compounds formed in solution, and also on the influence of concentration and nature of cations on stability and nature of the formed solid. The author first presents methods used in this study, discusses their precision and scope of validity. She reports the study of the formation of different complex ions which have been highlighted in solution, and the determination of their formation constants. She reports the preparation and study of the stability domain of solid complexes. The next part reports the use of thermogravimetric analysis, IR spectrometry, and crystallography for the structural study of these compounds

Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer

International Nuclear Information System (INIS)

Lima, Clarice Maria de

2011-01-01

Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with β - emitting radioisotopes. The Substance P (SP) is an 11- amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH 2 . The use of SP labeled with different radionuclides including 177 Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, over expressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with 177 Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity of lutetium-177 chloride and mass of DOTA-SP. The radiochemical purity of preparations were analyzed by chromatographic techniques. The stability of 17L u -DOTA- SP radiolabeled with low activity of 177 Lu was evaluated for different time at 2-8 degree C or incubated in human serum. The stability of the labeled with high activity of 177 Lu was also analyzed in the presence of gentisic acid (6 mg / mL) added after the labeling reaction. The labeled conditions in low and high activity were subjected to evaluation for the ability to cause oxidation of methionine residue, adding the D-L- methionine amino acid to the reaction medium (6 mg / mL) and subsequent chromatographic evaluation. In vitro study with 177 Lu-DOTA-SP, radiolabeled in the absence and presence

5 CFR 177.106 - Authority to adjust, determine, compromise, and settle.

Science.gov (United States)

2010-01-01

... SERVICE REGULATIONS ADMINISTRATIVE CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT § 177.106 Authority to adjust... alleged negligence or wrongful act or omission of an OPM employee, with the exception of claims involving...

Development of a therapeutic radiopharmaceutical 177Lu-DOTA- Minigastrin for potential use in PRRT

International Nuclear Information System (INIS)

Lopez Bularte, A.C.; Nevares, N.N.; Zapata, A.M.; Perez, J.H.; Crudo, J.L.; Puerta Yepes, N.; Rojo, A.M.

2010-01-01

The aim of this work is to obtain 177 Lu-DOTA-Minigastrin with high radiochemical purity (RP) and the highest specific activity (Ae) as possible, using a locally produced (Nuclear Reactor RA-3, Ezeiza Atomic Center) 177 LuCl 3 of an intermediate level of Ae (between 6.36 to 17.95 Ci/mg of 176 Lu) ) and also to perform in vitro and in vivo stability tests, dose calculation in normal mice and its extrapolation to a human model. (authors) [es

Long-term toxicity of [177Lu-DOTA0,Tyr3]octreotate in rats

International Nuclear Information System (INIS)

Rolleman, Edgar J.; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Bijster, Magda; Jong, Marion de; Visser, Theo J.; Vermeij, Marcel; Lindemans, Jan

2007-01-01

Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models. Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine levels rose significantly after 555 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores were maximal after 555 MBq and significantly lower in the 278 and 2 x 278 MBq groups. Three doses of 185 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469±18, 134±70 and 65±15 μmol/l, respectively; p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage. (orig.)

Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice

International Nuclear Information System (INIS)

Schüler, Emil; Rudqvist, Nils; Parris, Toshima Z.; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2014-01-01

Introduction: The kidneys are one of the main dose limiting organs in 177 Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from 177 Lu-octreotate exposure. Methods: Female Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq 177 Lu-octreotate. The animals were killed 24 h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes. Results: Distinct transcriptional responses were observed following 177 Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex. Conclusion: Specific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues

177Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable effectiveness to 213Bi-immunotherapy, but causes toxicity not observed with 213Bi

International Nuclear Information System (INIS)

Seidl, Christof; Zoeckler, Christine; Beck, Roswitha; Senekowitsch-Schmidtke, Reingard; Quintanilla-Martinez, Leticia; Bruchertseifer, Frank

2011-01-01

213 Bi-d9MAb-immunoconjugates targeting gastric cancer cells have effectively cured peritoneal carcinomatosis in a nude mouse model following intraperitoneal injection. Because the β-emitter 177 Lu has proven to be beneficial in targeted therapy, 177 Lu-d9MAb was investigated in this study in order to compare its therapeutic efficacy and toxicity with those of 213 Bi-d9MAb. Nude mice were inoculated intraperitoneally with HSC45-M2 gastric cancer cells expressing d9-E-cadherin and were treated intraperitoneally 1 or 8 days later with different activities of specific 177 Lu-d9MAb immunoconjugates targeting d9-E-cadherin or with nonspecific 177 Lu-d8MAb. Therapeutic efficacy was evaluated by monitoring survival for up to 250 days. For evaluation of toxicity, both biodistribution of 177 Lu-d9MAb and blood cell counts were determined at different time points and organs were examined histopathologically. Treatment with 177 Lu-immunoconjugates (1.85, 7.4, 14.8 MBq) significantly prolonged survival. As expected, treatment on day 1 after tumour cell inoculation was more effective than treatment on day 8, and specific 177 Lu-d9MAb conjugates were superior to nonspecific 177 Lu-d8MAb. Treatment with 7.4 MBq of 177 Lu-d9MAb was most successful, with 90% of the animals surviving longer than 250 days. However, treatment with therapeutically effective activities of 177 Lu-d9MAb was not free of toxic side effects. In some animals lymphoblastic lymphoma, proliferative glomerulonephritis and hepatocarcinoma were seen but were not observed after treatment with 213 Bi-d9MAb at comparable therapeutic efficacy. The therapeutic efficacy of 177 Lu-d9MAb conjugates in peritoneal carcinomatosis is impaired by toxic side effects. Because previous therapy with 213 Bi-d9MAb revealed comparable therapeutic efficacy without toxicity it should be preferred for the treatment of peritoneal carcinomatosis. (orig.)

21 CFR 177.1020 - Acrylonitrile/butadiene/sty-rene co-polymer.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Acrylonitrile/butadiene/sty-rene co-polymer. 177... SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances.../butadiene/sty-rene co-polymer. Acrylonitrile/butadiene/styrene copolymer identified in this section may be...

Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with {sup 177}Lu for tumors therapy that expressing αβ integrin s; Sistema monomerico, dimerico y multimerico de peptidos de RGD radiomarcados con {sup 177}Lu para terapia de tumores que expresan integrinas αβ

Energy Technology Data Exchange (ETDEWEB)

Luna G, M. A.

2014-07-01

The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of {sup 177}Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of {sup 177}Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential {sup 177}Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain {sup 177}Lu-AuNP-c[RGDfK(C)], the {sup 177}Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. {sup 177}Lu-DOTA-GGC, {sup 177}Lu- DOTA-cRGDfK and {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} were prepared by adding {sup 177}LuCl{sub 3} (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with {sup 177}Lu

Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer {sup 177}Lu-AMBA

Energy Technology Data Exchange (ETDEWEB)

Waser, Beatrice; Eltschinger, Veronique; Reubi, Jean C. [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Bern (Switzerland); Linder, Karen; Nunn, Adrian [Bracco Research USA Inc, Princeton, NJ (United States)

2007-01-15

To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, {sup 177}Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3. In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand {sup 177}Lu-AMBA was used and compared with established bombesin radioligands such as {sup 125}I-Tyr{sup 4}-bombesin and {sup 125}I-[D-Tyr{sup 6},{beta}-Ala{sup 11},Phe{sup 13},Nle{sup 14}]-bombesin(6-14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. {sup 177}Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. {sup 177}Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with {sup 177}Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with {sup 177}Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with {sup 177}Lu-AMBA than with the conventional bombesin radioligands. The present in vitro study suggests that {sup 177}Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessels. (orig.)

Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol.

Science.gov (United States)

Olmstead, Craig; Cruz, Kyle; Stodilka, Robert; Zabel, Pamela; Wolfson, Robert

2015-02-01

Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis. Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients' rooms to assess the potential cumulative radiation exposure during the initial 30 min-4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4-20 h after treatment (simulating the discharged outpatient portion). The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv. Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public.

CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities

Energy Technology Data Exchange (ETDEWEB)

Wu, Cheng-Jang [Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China); Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093 (United States); Lu, Chun-Hao [Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China); Chen, Li-Chen [Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan (China); Nguyen, Duc T. [Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093 (United States); Huang, Yi-Shu [Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China); Lin, Hsi-Hsien [Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China); Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan (China); Department of Anatomic Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan (China); Lin, Chun-Yen [Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China); Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan (China); Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan (China); Kuo, Ming-Ling, E-mail: mingling@mail.cgu.edu.tw [Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan (China); Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan (China); Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan (China)

2016-05-13

Non-depleting YTS177 anti-CD4 monoclonal antibody (MoAb) has been reported to lead to antigen-specific immunotolerance in allograft transplantation and autoimmune diabetes, as well as possibly to inhibition of allergic inflammation in mice. However, the molecular mechanisms underlying hyporesponsive T cell responses induced by YTS177 MoAb remain elusive. Herein, we demonstrate that the YTS177 MoAb increases the levels of anergy factors p27{sup kip1} and Cbl-b, inhibits IL-2 production, and impairs calcium mobilization in activated T cells in vitro. YTS177 MoAb suppresses OVA-driven proliferation of DO11.10 CD4{sup +} T cells in vivo as well. Mechanistically, YTS177 MoAb induces tolerance by causing CD4 down-regulation through clathrin-dependent and raft dissociation. The results obtained in this study lead us to propose novel protective or curative approaches to CD4 T cell-mediated diseases.

CD4 down regulation and raft dissociation by the non-depleting YTS177 antibody hinder murine T helper cell activities

International Nuclear Information System (INIS)

Wu, Cheng-Jang; Lu, Chun-Hao; Chen, Li-Chen; Nguyen, Duc T.; Huang, Yi-Shu; Lin, Hsi-Hsien; Lin, Chun-Yen; Kuo, Ming-Ling

2016-01-01

Non-depleting YTS177 anti-CD4 monoclonal antibody (MoAb) has been reported to lead to antigen-specific immunotolerance in allograft transplantation and autoimmune diabetes, as well as possibly to inhibition of allergic inflammation in mice. However, the molecular mechanisms underlying hyporesponsive T cell responses induced by YTS177 MoAb remain elusive. Herein, we demonstrate that the YTS177 MoAb increases the levels of anergy factors p27"k"i"p"1 and Cbl-b, inhibits IL-2 production, and impairs calcium mobilization in activated T cells in vitro. YTS177 MoAb suppresses OVA-driven proliferation of DO11.10 CD4"+ T cells in vivo as well. Mechanistically, YTS177 MoAb induces tolerance by causing CD4 down-regulation through clathrin-dependent and raft dissociation. The results obtained in this study lead us to propose novel protective or curative approaches to CD4 T cell-mediated diseases.

Internal radiotherapy and dosimetric study for {sup 111}In/{sup 177}Lu-pegylated liposomes conjugates in tumor-bearing mice

Energy Technology Data Exchange (ETDEWEB)

Wang, H.-E. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Yu, H.-M. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lu, Y.-C. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Heish, N.-N. [National Health Research Institute, Taipei, Taiwan (China); Tseng, Yun-Long [Taiwan Liposome Co. Ltd., Taipei, Taiwan (China); Huang, K.-L. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chuang, K.-T. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, Chin-Hsiung [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Hwang, J.-J. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lin, W.-J. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Wang, Shyh-Jen [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Ting, G. [National Health Research Institute, Taipei, Taiwan (China); Whang-Peng, Jacqueline [National Health Research Institute, Taipei, Taiwan (China); Deng, W.-P. [Graduate Institute of Biomedical Materials, Taipei Medical University, Taipei, Taiwan (China)]. E-mail: wpdeng@tmu.edu.tw

2006-12-20

In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with {sup 111}In/{sup 177}Lu-(oxine){sub 3} to afford {sup 111}In/{sup 177}Lu-liposome. The stability of {sup 111}In/{sup 177}Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of {sup 111}In/{sup 177}Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of {sup 111}In/{sup 177}Lu into liposomes was 95%. After incubation at 37 {sup o}C for 72 h in serum, more than 83% of radioactivity was still retained in the intact {sup 111}In/{sup 177}Lu-liposomes. The biodistribution of {sup 111}In-liposomes showed that the radioactivity in the blood decreased from 23.14{+-}8.16%ID/g at 1 h to 0.02{+-}0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of {sup 177}Lu-liposomes. Scintigraphic imaging with {sup 111}In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from {sup 177}Lu-liposomes was 5.74x10{sup -5} Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes.

49 CFR 38.177 - Ferries, excursion boats and other vessels. [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Ferries, excursion boats and other vessels... DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES Other Vehicles and Systems § 38.177 Ferries, excursion boats and other vessels. [Reserved] ...

Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections

DEFF Research Database (Denmark)

de Nijs, Robin; Lagerburg, Vera; Klausen, Thomas L

2014-01-01

and the activity, which depends on the collimator type, the utilized energy windows and the applied scatter correction techniques. In this study, energy window subtraction-based scatter correction methods are compared experimentally and quantitatively. MATERIALS AND METHODS: (177)Lu SPECT images of a phantom...... technique, the measured ratio was close to the real ratio, and the differences between spheres were small. CONCLUSION: For quantitative (177)Lu imaging MEGP collimators are advised. Both energy peaks can be utilized when the ESSE correction technique is applied. The difference between the calculated...

Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

International Nuclear Information System (INIS)

Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de; Vermeij, Marcel

2007-01-01

In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Male Lewis rats were injected with 278 or 555 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of 99m Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of 99m Tc-DMSA SPECT scintigrams at 130 days after [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate therapy correlated well with 1/creatinine (r 2 = 0.772, p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy. (orig.)

A search for long-lived radionuclides produced by fast-neutron irradiations of copper, silver, europium, terbium, and hafnium

International Nuclear Information System (INIS)

Meadows, J.W.; Smith, D.L.; Ikeda, Y.; Konno, C.

1990-01-01

Identical sample packets, each containing samples of elemental copper, silver, europium, terbium, and hafnium, as well as titanium, iron and nickel as dosimeters, have been irradiated in three distinct accelerator neutron fields (at Argonne National Laboratory and Los Alamos National Laboratory in the U.S.A., and Japan Atomic Energy Research Institute, Tokai, Japan) as part of an interlaboratory research collaboration to search for the production of long-lived radionuclides for fusion waste disposal applications. This paper is a progress report on this project. To date, we have detected the following activities, and have obtained preliminary experimental cross section values for several of these: Ag-106m,108m,110m; Eu-150m,152g,154; Tb-158,160; and Hf-175,178m2,179m2,181. (author). 11 refs, 1 fig., 4 tabs

Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with 177Lu for tumors therapy that expressing αβ integrin s

International Nuclear Information System (INIS)

Luna G, M. A.

2014-01-01

The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of 177 Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of 177 Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential 177 Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain 177 Lu-AuNP-c[RGDfK(C)], the 177 Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. 177 Lu-DOTA-GGC, 177 Lu- DOTA-cRGDfK and 177 Lu-DOTA-E-c(RGDfK) 2 were prepared by adding 177 LuCl 3 (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with 177 Lu-AuNP-c[RGDfK(C)], the MCF7 cell proliferation was significantly inhibited

21 CFR 177.1360 - Ethylene-vinyl acetate-vinyl alcohol copolymers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene-vinyl acetate-vinyl alcohol copolymers... for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1360 Ethylene-vinyl acetate-vinyl alcohol copolymers. Ethylene-vinyl acetate-vinyl alcohol copolymers (CAS Reg. No. 26221-27-2...

Ferroelectric transistors with monolayer molybdenum disulfide and ultra-thin aluminum-doped hafnium oxide

Science.gov (United States)

Yap, Wui Chung; Jiang, Hao; Liu, Jialun; Xia, Qiangfei; Zhu, Wenjuan

2017-07-01

In this letter, we demonstrate ferroelectric memory devices with monolayer molybdenum disulfide (MoS2) as the channel material and aluminum (Al)-doped hafnium oxide (HfO2) as the ferroelectric gate dielectric. Metal-ferroelectric-metal capacitors with 16 nm thick Al-doped HfO2 are fabricated, and a remnant polarization of 3 μC/cm2 under a program/erase voltage of 5 V is observed. The capability of potential 10 years data retention was estimated using extrapolation of the experimental data. Ferroelectric transistors based on embedded ferroelectric HfO2 and MoS2 grown by chemical vapor deposition are fabricated. Clockwise hysteresis is observed at low program/erase voltages due to slow bulk traps located near the 2D/dielectric interface, while counterclockwise hysteresis is observed at high program/erase voltages due to ferroelectric polarization. In addition, the endurances of the devices are tested, and the effects associated with ferroelectric materials, such as the wake-up effect and polarization fatigue, are observed. Reliable writing/reading in MoS2/Al-doped HfO2 ferroelectric transistors over 2 × 104 cycles is achieved. This research can potentially lead to advances of two-dimensional (2D) materials in low-power logic and memory applications.

Radionuclide therapy with tissue factor targeting Lu-177-FVIIai inhibits growth in an experimental mouse model of human pancreatic cancer

DEFF Research Database (Denmark)

Nielsen, Carsten; Jensen, Mette; Fonslet, Jesper

2017-01-01

in several organs at 1, 4, 24, 72 and 168 hours after injection. The in vivo biodistribution of 177Lu-FVIIai was evaluated by SPECT/CT imaging. Furthermore, competition and dose escalation experiments (1-30 MBq) were performed. In a parallel set of NMRI mice, toxic effects of 177Lu-FVIIai were evaluated...... by hematology, histology and 99mTc-DMSA scintigraphy. Results: FVIIai was successfully radiolabeled with 177Lu with a specific activity of 10-25 GBq/µmol after EDTA scavenging and PD-10 purification. Treatment with FVIIai did not change tumor growth compared to the vehicle groups. The mice that received 15 MBq...... uptake of 177Lu-FVIIai measured ex vivo was 1.16±0.04, 1.97±0.18, 1.95±0.07, 1.01±0.06, 0.31±0.02 percent injected dose per gram (%ID/g) at 1, 4, 24, 72 and 168 hours post-injection, respectively. Injection with unlabeled FVIIai 10 minutes before 177Lu-FVIIai injection significantly reduced tumor uptake...

Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent

International Nuclear Information System (INIS)

Mathe, Domokos; Balogh, Lajos; Polyak, Andras; Kiraly, Reka; Marian, Terez; Pawlak, Dariusz; Zaknun, John J.; Pillai, Maroor R.A.; Janoki, Gyozo A.

2010-01-01

Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low β- energy, 177 Lu [T 1/2 =6.73 days, E βmax =497 keV, E γ =113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of 177 Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: 177 Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of 177 Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: 177 Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of 177 Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing 177 Lu does not alter its biological behaviour as a specific bone-seeking tracer. Species-specific pharmacokinetic behavior

Production of non carrier added (n.c.a.) {sup 177}Lu for radiopharmaceutical applications

Energy Technology Data Exchange (ETDEWEB)

Barkhausen, Christoph

2011-09-06

The goal of this dissertation was the development of a process to produce non carrier added {sup 177}Lu at the FRM II. For this purpose, preparative chromatographic methods were evaluated and applied. The highest quality of the nuclide which could only be achieved through a complex chemical process, has been already been proven by clinical studies to be very advantageous. The process has been built up in a hot cell as a semi-automated process and is now being adapted to the requirements of the 'Arzneimittelgesetz' in order to establish n.c.a. {sup 177}Lu as a pharmaceutical product.

Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.

Science.gov (United States)

Zhang, Jingjing; Wang, Hao; Jacobson Weiss, Orit; Cheng, Yuejuan; Niu, Gang; Li, Fang; Bai, Chunmei; Zhu, Zhaohui; Chen, Xiaoyuan

2018-04-13

Radiolabeled somatostatin analogue therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogues in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-human study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analogue, lutetium-177-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate ( 177 Lu-DOTA-EB-TATE). Methods: Eight patients (6 males and 2 females; age range, 27-61 y) with advanced metastatic neuroendocrine tumors were recruited. Five patients received a single dose 0.35-0.70 GBq (9.5-18.9 mCi) of 177 Lu-DOTA-EB-TATE and underwent serial whole body planar and single-photon emission computed tomography-computed tomography (SPECT-CT) scans at 2, 24, 72, 120 and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177 Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24 and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Results: Administration of 177 Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared with 177 Lu-DOTATATE, 177 Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved 7.9-fold increase of tumor dose delivery. The total body effective doses were 0.205 ± 0.161 mSv/MBq for 177 Lu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for 177 Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receiving 177 Lu-DOTA-EB-TATE than those receiving 177 Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By introducing an albumin binding moiety, 177 Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NET

Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy.

Science.gov (United States)

Spetz, Johan; Rudqvist, Nils; Langen, Britta; Parris, Toshima Z; Dalmo, Johanna; Schüler, Emil; Wängberg, Bo; Nilsson, Ola; Helou, Khalil; Forssell-Aronsson, Eva

2018-05-01

Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed. Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively. Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents. Copyright © 2018 The Authors. Published by Elsevier Inc. All

46 CFR 177.600 - Ventilation of enclosed and partially enclosed spaces.

Science.gov (United States)

2010-10-01

... ventilation system unless natural ventilation in all ordinary weather conditions is satisfactory to the OCMI... 46 Shipping 7 2010-10-01 2010-10-01 false Ventilation of enclosed and partially enclosed spaces... PASSENGER VESSELS (UNDER 100 GROSS TONS) CONSTRUCTION AND ARRANGEMENT Ventilation § 177.600 Ventilation of...

Improvement in the 111In-DTPA-TYR3-octreotide and 177Lu-DOTATYR3- octreotate production

International Nuclear Information System (INIS)

Souza, Adriano A.; Herrerias, Rosana; Pires, Jose A.; Alves, Geraldo P.; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Almeida, Erika V.; Mengatti, Jair; Barboza, Marycel F. de

2009-01-01

Recent advances in receptor mediated-tumor imaging have resulted in the development of somatostatin analogues, the biomolecular basis for the clinical use of these compounds in nuclear medicine for diagnostic and peptide receptor radionuclide therapy (PRRT). PRRT is a very good therapeutic option for patients with metastatic neuroendocrine gastroenteropancreatic (GEP) tumour. Clinical studies with different sst-positives tumors proved advantages of [ 177 Lu-DOTA-Tyr 3 ]octreotate (DOTATATE) for therapy. The aim of this work is to establish and validate the labeling, the quality control procedures of DTPA-Tyr 3 -Octreotide (DTPA-Oct) and DOTA-Tyr 3 -Octreotate (DOTATATE) labeled with In-111 and Lu-177, respectively, for routine production at Radiopharmacy Directory (DIRF) Brazil. Labeling were performed in a 'glove-box' using 111 InCl 3 (Nordion) and in hot-cell with 177 LuCl 3 (IDB-Holland) at pH 4.5; using DTPA-Oct (Pichem) and DOTATATE (IDBHolland) at room temperature and at 82-85 deg C for 30 minutes, respectively. The radiochemical purity was determined by ITLC-SG in 0.1 mol L -1 sodium citrate, pH 5.5 and by Sep-Pak silica cartridge. Sterility was performed by the microbiology procedures and pyrogen tests by the 'in-vitro' Limulus test (LAL). The stability of both radiolabeled peptides was high even 72 hours under refrigeration. The radiochemical purities of the labeled compounds were confirmed by HPLC. Sterility and pyrogen tests were negative in all delivered vials. The efficient procedure to obtain 111 In-DTPA-Oct and 177 Lu-DOTATATE was confirmed in the first comparative clinical groups. The methods were validated and 46.287 GMBq of 111 In-DTPA-Oct and 1,193 GBq of 177 Lu-DOTATATE were distributed in 2008, to nuclear medicine services in Brazil. (author)

Preparation and bioevaluation of {sup 177}Lu-labelled anti-CD44 for radioimmunotherapy of colon cancer

Energy Technology Data Exchange (ETDEWEB)

Lee, So Young; Hong, Young Don; Jung, Sung Hee; Choi, Sun Ju [Radioisotope Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-12-15

CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the {sup 177}Lu-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based dtPA-ncS and radioimmunoconjugated with {sup 177}Lu at room temperature within 15 minutes. the stability was tested in human serum. An in vitro study was carried out in Ht-29 human colon cancer cell lines. For the biodistribution study {sup 177}Lu-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteinebased dtPA-ncS and purified by a centricon filter system having a molecular cut-off of 50 kda. radioimmunoconjugation with {sup 177}Lu was reacted for 15 min at room temperature. the radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. the anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with {sup 177}Lu. the in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. this radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

Subacute haematotoxicity after PRRT with {sup 177}Lu-DOTA-octreotate: prognostic factors, incidence and course

Energy Technology Data Exchange (ETDEWEB)

Bergsma, Hendrik; Konijnenberg, Mark W.; Kam, Boen L.R.; Teunissen, Jaap J.M.; Kooij, Peter P.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Franssen, Gaston J.H.; Eijck, Casper H.J. van [Erasmus Medical Center, Department of Surgery, Rotterdam (Netherlands)

2016-03-15

In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from {sup 131}I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with {sup 177}Lu-DOTA{sup 0}-Tyr{sup 3}-octreotate ({sup 177}Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit. The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined. Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 x 10{sup 9}/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq {sup 177}Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients. The incidence of subacute haematological toxicity after PRRT with {sup 177}Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from {sup 131}I, seems not to be valid for PRRT with {sup 177}Lu-DOTATATE. (orig.)

29 CFR 4.177 - Discharging fringe benefit obligations by equivalent means.

Science.gov (United States)

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Discharging fringe benefit obligations by equivalent means... CONTRACTS Compensation Standards Compliance with Compensation Standards § 4.177 Discharging fringe benefit obligations by equivalent means. (a) In general. (1) Section 2(a)(2) of the Act, which provides for fringe...

77 FR 6536 - Approval for Manufacturing Authority; Foreign-Trade Zone 177; Best Chair, Inc., d/b/a Best Home...

Science.gov (United States)

2012-02-08

... manufacturing authority on behalf of Best Chair, Inc., d/ b/a Best Home Furnishings, Inc., within FTZ 177 in... application for manufacturing authority under zone procedures within FTZ 177 on behalf of Best Chair, Inc., d... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [Order No. 1807] Approval for Manufacturing...

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)

{sup 177}Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India

Energy Technology Data Exchange (ETDEWEB)

Danthala, Madhav; Raghavendra Rao, M. [HCG Oncology Hospitals, Bangalore, Karnataka (India); Kallur, K.G.; Prashant, G.R.; Rajkumar, K. [HCG Oncology Hospitals, Department of Nuclear Medicine, Bangalore, Karnataka (India)

2014-07-15

The choice of an appropriate treatment option in patients with inoperable or metastatic neuroendocrine tumours (NETs) is limited, and approximately 50 % of patients have advanced NET at diagnosis, and 65 % die within 5 years. Treatment with {sup 177}Lu-DOTATATE ({sup 177}Lu-[DOTA{sup 0},Tyr{sup 3}] octreotate) is a promising new option in the treatment of metastatic NETs. Patients with metastatic NET who underwent {sup 177}Lu-DOTATATE during the period 2009 to 2013 were included in this retrospective study. Follow-up imaging studies including a {sup 68}Ga-DOTANOC PET/CT scan and a posttherapy {sup 177}Lu-DOTATATE scan were compared with baseline imaging to determine response to treatment. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and Cox regression analysis was also done. Ten patients (25 %) had a minimal response, 13 (32.5 %) had a partial response and 9 (22.5 %) had stable disease. Progressive disease was seen in 8 patients (20 %), including 6 patients who died during or after the treatment period. The estimated mean PFS in those who received one or two cycles of {sup 177}Lu-DOTATATE was 8.3 months (95 % CI 6.2 to 10.3 months) compared to an estimated mean PFS of 45.6 months (95 % CI 40.9 to 50.2 months) in those who received more than two cycles of {sup 177}Lu-DOTATATE (log-rank Mantel-Cox Χ {sup 2} = 8.01, p = 0.005). Our study showed that treatment with {sup 177}Lu-DOTATATE should be considered in the management of NETs, considering the limited success of alternative treatment modalities. Treatment response and PFS is determined primarily by the dose delivered and best results are obtained when more than two cycles of {sup 177}Lu-DOTATATE are given, with careful monitoring for possible side effects. (orig.)

Targeted radiotherapy with 177 Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

International Nuclear Information System (INIS)

Rodriguez C, J.; Murphy, C.A. de; Pedraza L, M.; Ferro F, G.; Murphy S, E.

2006-01-01

Malignant pancreas tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses after administration of 177 Lu-DOTA-TATE in mice as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (n=18) to obtain the 177 Lu-DOTA-TATE biokinetics and dosimetry. To estimate its therapeutic efficacy 87 MBq were injected in a tail vein of 3 mice and 19 days p.i. there were a partial relapse. There was an epithelial and sarcoma mixed tumour in the kidneys of mouse III. The absorbed dose to tumour, kidney and pancreas was 50.5 ± 7.2 Gy, 17.5 ± 2.5 Gy and 12.6 ± 2.3 Gy respectively. These studies justify further therapeutic and dosimetry estimations to ensure that 177 Lu-DOTA-TATE will act as expected in man considering its kidney radiotoxicity. (Author)

Tumor-targeting properties of 90Y- and 177Lu-labeled α-melanocyte stimulating hormone peptide analogues in a murine melanoma model

International Nuclear Information System (INIS)

Miao Yubin; Hoffman, Timothy J.; Quinn, Thomas P.

2005-01-01

The purpose of this study was to compare the tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were 25.70±4.64 and 14.48±0.85 %ID/g at 2 h, and 14.09±2.73 and 17.68±3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations

Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of {sup 177}Lu-EDTMP, a potential bone pain palliation agent

Energy Technology Data Exchange (ETDEWEB)

Mathe, Domokos [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)], E-mail: mdomokos@hp.osski.hu; Balogh, Lajos; Polyak, Andras; Kiraly, Reka [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary); Marian, Terez [Institute of Nuclear Medicine, Debrecen University, Debrecen (Hungary); Pawlak, Dariusz [Institute of Atomic Energy, Radioisotope Centre POLATOM, Swierk-Otwock (Poland); Zaknun, John J.; Pillai, Maroor R.A. [International Atomic Energy Agency (IAEA), Vienna (Austria); Janoki, Gyozo A. [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)

2010-02-15

Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low {beta}- energy, {sup 177}Lu [T{sub 1/2}=6.73 days, E{sub {beta}}{sub max}=497 keV, E{sub {gamma}}=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of {sup 177}Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: {sup 177}Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of {sup 177}Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: {sup 177}Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of {sup 177}Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing {sup 177}Lu does not alter its biological behaviour as a specific bone

Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects.

Science.gov (United States)

Mathur, Anupam; Prashant, Vrinda; Sakhare, Navin; Chakraborty, Sudipta; Vimalnath, K V; Mohan, Repaka Krishna; Arjun, Chanda; Karkhanis, Barkha; Seshan, Ravi; Basu, Sandip; Korde, Aruna; Banerjee, Sharmila; Dash, Ashutosh; Sachdev, Satbir Singh

2017-09-01

177 Lu-DOTA-TATE is a clinically useful and promising therapeutic radiopharmaceutical for peptide receptor radionuclide therapy of neuroendocrine tumors (NETs) overexpressing somatostatin receptors. Currently, the radiopharmaceutical is prepared in-house at nuclear medicine centers, thereby restricting its use to limited centers only. In this article, the authors describe systematic studies toward bulk scale formulation of "ready-to-use" 177 Lu-DOTA-TATE using medium specific activity 177 Lu (740-1110 GBq/mg) at a centralized radiopharmacy facility. In an optimized protocol, 177 Lu-DOTA-TATE synthesis was carried out by direct heating of 177 LuCl 3 (Sp. act. 740-1110 GBq/mg) with DOTA-TATE peptide (1.5-3.0 equivalents) in ammonium acetate buffer (0.2 M) containing 2,5-dihydroxy benzoic acid (gentisic acid). Thereafter, the crude labeled product was purified using a Sep-Pak ® C18 column and diluted with acetate buffer-gentisic acid (1.5% w/v) solution to final radioactive concentration of 740 MBq/mL. This was further sterilized and dispensed as 7.4 GBq patient dose/vial with 2 days postformulation calibration. A peptide/metal ratio of 1.5-3.0 is essential for complexation wherein radiolabeling yields >90% are obtained minimizing free 177 Lu waste. For formulation of 7.4 GBq patient dose (2 days postproduction), even specific activity of about 555 GBq/mg was found to be adequate for the radiometal. The ready-to-use 740 MBq/mL 177 Lu-DOTA-TATE formulation with gentisic acid (1.5% w/v) is observed to be safe for human use for more than 1 week (radiochemical purity >98%) from the day of production when stored at -70°C. However, the target specificity may get affected beyond 2 days as the total peptide content for 7.4 GBq dose may exceed the critical peptide limit of 300 μg. Patient treatment carried with several batches of present formulation in diseased NET patients exhibited desired distribution at the tumor and its metastatic site. A ready

49 CFR 177.823 - Movement of motor vehicles in emergency situations.

Science.gov (United States)

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Movement of motor vehicles in emergency situations... CARRIAGE BY PUBLIC HIGHWAY General Information and Regulations § 177.823 Movement of motor vehicles in... government; (2) The carrier has permission from the Department; or (3) Movement of the transport vehicle is...

46 CFR 177.620 - Ventilation of machinery and fuel tank spaces.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Ventilation of machinery and fuel tank spaces. 177.620... fuel tank spaces. In addition to the requirements of this subpart, ventilation systems for spaces containing machinery or fuel tanks must comply with the requirements of part 182 of this chapter. ...

Report on the 1. research coordination meeting on 'Development of therapeutic radiopharmaceuticals based on 177Lu for radionuclide therapy'

International Nuclear Information System (INIS)

2006-01-01

Radionuclide therapy (RNT) employing radiopharmaceuticals labelled with emitting radionuclides is fast emerging as an important part of nuclear medicine. Radionuclide therapy is effectively utilized for bone pain palliation, thus providing significant improvement in quality of life of patients suffering from pain resulting from bone metastasis. Targeting primary diseases by using specific carrier molecules labelled with radionuclides is also widely investigated and efficacious products have been emerging for the treatment of Lymphoma and Neuroendocrine tumours. In order to ensure the wider use of radiopharmaceuticals, it is essential to carefully consider the choice of radionuclides that together with the carrier molecules will give suitable pharmacokinetic properties and therapeutic efficacy. The criteria for the selection of a radionuclide for radiotherapy are suitable decay characteristics and amenable chemistry. However, the practical considerations in selecting a radionuclide for targeted therapy are availability in high radionuclidic purity as well as high specific activity and low production cost and comfortable delivery logistics. 177 Lu is one of the isotopes emerging as a clear choice for therapy. Worldwide, the isotope is under investigation for approximately 30 different clinical applications, including treatment of colon cancer, metastatic bone cancer, non-Hodgkin's lymphoma, and lung cancer. 177 Lu decays with a half-life of 6.71 d by emission of particles with E max of 497 keV (78.6%), 384 keV (9.1%) and 176 keV (12.2%). It also emits photons of 113 keV (6.4%) and 208 keV (11%), that are ideally suited for imaging the in-vivo localization and dosimetric calculations applying a gamma camera. The physical half-life of 177 Lu is comparable to that of 131 I, the most widely used therapeutic radionuclide. The long halflife of 177 Lu provides logistic advantage for production, QA/QC of the products as well as feasibility to supply the products to places

Somatostatin-based Radiopeptide Therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in Neuroendocrine Tumors

OpenAIRE

Romer A Seiler D Marincek N Brunner P Koller MT Ng QK Maecke HR Muller-Brand J Rochlitz C B

2014-01-01

PURPOSE: Somatostatin based radiopeptide treatment is generally performed using the ß emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. METHODS: In a comparative cohort study patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y DOTA] TOC or [(177)Lu DOTA] TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were emplo...

26 CFR 1.177-1 - Election to amortize trademark and trade name expenditures.

Science.gov (United States)

2010-04-01

... franchises or rights to the use of a trademark or trade name. Generally, section 177 will apply to... beginning after December 31, 1955, shall, within the time prescribed by law (including extensions thereof...

{sup 177}Lu-DOTMP: a viable agent for palliative radiotherapy of painful bone metastasis

Energy Technology Data Exchange (ETDEWEB)

Das, T.; Chakraborty, S.; Banerjee, S. [Radiopharmaceuticals Div., Bhabha Atomic Research Centre, Mumbai (India); Sarma, H.D. [Radiation Biology and Health Sciences Div., Bhabha Atomic Research Centre, Mumbai (India)

2008-07-01

The suitable nuclear decay characteristics [T{sub 1/2} = 6.73 d, E{sub {beta}}{sub (max)} = 497 keV, E{sub {gamma}} = 113 keV (6.4%), 208 keV (11%)] as well as the feasibility of large-scale production with adequate specific activity and radionuclidic purity using a moderate flux reactor are important attributes towards {sup 177}Lu to be considered as a promising radionuclide for palliative care in painful bone metastasis. The present study describes the preparation of {sup 177}Lu complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) and its preliminary biological evaluation in animal models with an aim to proposing it as a viable radiopharmaceutical for bone pain palliation. The choice DOTMP as the polyaminophosphonic acid carrier ligand is based on the enhanced thermodynamic stability and kinetic inertness of the metal-ligand complexes with macrocyclic chelators. {sup 177}Lu was produced with a specific activity of {proportional_to} 12 GBq/mg ({proportional_to} 324 mCi/mg) and radionuclidic purity of 99.98% by irradiation of natural Lu{sub 2}O{sub 3} target at a thermal neutron flux of {proportional_to} 6 x 10{sup 13} n/cm{sup 2} s for 21 d. {sup 177}Lu-DOTMP complex was prepared in high yield and excellent radiochemical purity (> 99%) using DOTMP synthesized and characterized in-house. The complex exhibited excellent in-vitro stability at room temperature. Biodistribution studies in Wistar rats showed rapid skeletal accumulation of the injected activity [(1.60{+-}0.19)% per gram in femur at 3 h post-injection] with fast clearance from blood and minimal uptake in any of the major organs. Scintigraphic studies carried out in normal Wistar rats and New Zealand white rabbits also demonstrated significant accumulation of the agent in skeleton and almost no retention in any other vital organs. (orig.)

In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy.

Science.gov (United States)

Chan, Ho Sze; de Blois, Erik; Morgenstern, Alfred; Bruchertseifer, Frank; de Jong, Marion; Breeman, Wouter; Konijnenberg, Mark

2017-01-01

Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET) nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE), 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line. Two other cell lines were used for radiation response assessment; BON and CA20948, with a low and high expression of somatostatin receptors, respectively. Cellular uptake kinetics of 111In-DOTATATE were determined in CA20948 cells. CA20948 and BON were irradiated with 137Cs, 177Lu-DTPA, 177Lu-DOTATATE, 213Bi-DTPA and 213Bi-DOTATATE. Absorbed doses were calculated using the MIRDcell dosimetry method for the specific binding and a Monte Carlo model of a cylindrical 6-well plate geometry for the exposure by the radioactive incubation medium. Absorbed doses were compared to conventional irradiation of cells with 137Cs and the relative biological effect (RBE) at 10% survival was calculated. IC50 of (labelled) DOTATATE was in the nM range. Absorbed doses up to 7 Gy were obtained by 5.2 MBq 213Bi-DOTATATE, in majority the dose was caused by α-particle radiation. Cellular internalization determined with 111In-DOTATATE showed a linear relation with incubation time. Cell survival after exposure of 213Bi-DTPA and 213Bi-DOTATATE to BON or CA20948 cells showed a linear-exponential relation with the absorbed dose, confirming the high LET character of 213Bi. The survival of CA20948 after exposure to 177Lu-DOTATATE and the reference 137Cs irradiation showed the typical curvature of the linear-quadratic model. 10% Cell survival of CA20948 was reached at 3 Gy with 213Bi-DOTATATE, a factor 6 lower than the 18 Gy found for 177Lu

In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy.

Directory of Open Access Journals (Sweden)

Ho Sze Chan

Full Text Available Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE, 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line. Two other cell lines were used for radiation response assessment; BON and CA20948, with a low and high expression of somatostatin receptors, respectively. Cellular uptake kinetics of 111In-DOTATATE were determined in CA20948 cells. CA20948 and BON were irradiated with 137Cs, 177Lu-DTPA, 177Lu-DOTATATE, 213Bi-DTPA and 213Bi-DOTATATE. Absorbed doses were calculated using the MIRDcell dosimetry method for the specific binding and a Monte Carlo model of a cylindrical 6-well plate geometry for the exposure by the radioactive incubation medium. Absorbed doses were compared to conventional irradiation of cells with 137Cs and the relative biological effect (RBE at 10% survival was calculated.IC50 of (labelled DOTATATE was in the nM range. Absorbed doses up to 7 Gy were obtained by 5.2 MBq 213Bi-DOTATATE, in majority the dose was caused by α-particle radiation. Cellular internalization determined with 111In-DOTATATE showed a linear relation with incubation time. Cell survival after exposure of 213Bi-DTPA and 213Bi-DOTATATE to BON or CA20948 cells showed a linear-exponential relation with the absorbed dose, confirming the high LET character of 213Bi. The survival of CA20948 after exposure to 177Lu-DOTATATE and the reference 137Cs irradiation showed the typical curvature of the linear-quadratic model. 10% Cell survival of CA20948 was reached at 3 Gy with 213Bi-DOTATATE, a factor 6 lower than the 18 Gy found

ECCS analysis of B and W's 177-FA lowered-loop NSS

International Nuclear Information System (INIS)

Jones, R.C.; Biller, J.R.; Dunn, B.M.

1975-06-01

The effectiveness for the ECCS for B and W's 177-FA Lowered-Loop NSS is shown to meet the five criteria of 10 CFR 50.46. A spectrum analysis is performed and the worst case is used to establish allowable linear heat rates as a function of elevation in the core. (U.S.)

Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy.

Science.gov (United States)

Seregni, E; Maccauro, M; Chiesa, C; Mariani, L; Pascali, C; Mazzaferro, V; De Braud, F; Buzzoni, R; Milione, M; Lorenzoni, A; Bogni, A; Coliva, A; Lo Vullo, S; Bombardieri, E

2014-02-01

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ((90)Y) and a medium-energy beta/gamma emitter ([(177)Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [[(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [[(177)Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [(90)Y]DOTA-TATE and [[(177)Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment. The results of our study indicates that combined [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach.

An assessment tumor targeting ability of 177Lu labeled cyclic CCK analogue peptide by binding with cholecystokinin receptor

Directory of Open Access Journals (Sweden)

Eun-Ha Cho

2016-07-01

Full Text Available The cholecystokinin (CCK receptor is known as a receptor that is overexpressed in many human tumors. The present study was designed to investigate the targeting ability of cyclic CCK analogue in AR42J pancreatic cells. The CCK analogues, DOTA-K(glucose-Gly-Trp-Nle-Asp-Phe (DOTA-glucose-CCK and DOTA-Nle-cyclo(Glu-Trp-Nle-Asp-Phe-Lys-NH2 (DOTA-[Nle]-cCCK, were synthesized and radiolabeled with 177Lu, and competitive binding was evaluated. The binding appearance of synthesized peptide with AR42J cells was evaluated by confocal microscopy. And bio-distribution was performed in AR42J xenografted mice. Synthesized peptides were prepared by a solid phase synthesis method, and their purity was over 98%. DOTA is the chelating agent for 177Lu-labeling, in which the peptides were radiolabeled with 177Lu by a high radiolabeling yield. A competitive displacement of 125I-CCK8 on the AR42J cells revealed that the 50% inhibitory concentration value (IC50 was 12.3 nM of DOTA-glucose-CCK and 1.7 nM of DOTA-[Nle]-cCCK. Radio-labeled peptides were accumulated in AR42J tumor in vivo, and %ID/g of the tumor was 0.4 and 0.9 at 2 h p.i. It was concluded that 177Lu-DOTA-[Nle]-cCCK has higher binding affinity than 177Lu-DOTA-glucose-CCK and can be a potential candidate as a targeting modality for a CCK receptor over-expressing tumors.

Study On Preparation Of 177Lu-EDTMP For Metastatic Bone Pain Palliation Treatment

International Nuclear Information System (INIS)

Nguyen Thanh Binh; Dang Ho Hong Quang; Duong Van Dong; Chu Van Khoa; Nguyen Thi Hien

2011-01-01

Ethylene diamine tetramethylene phosphonate (EDTMP) is one of the most widely used ligands which forms stable complexes with various radionuclides and all the complexes showed high bone uptake in biodistribution studies. EDTMP has a high affinity to skeleton and osteoblastic bone metastases and many EDTMP chelates posses a considerably high stability.This stimulated application of the ligand as the in-vivo carrier of various radionuclides, intended for both therapy and diagnosis of osteoblastic lesions.The present study intends to formulate EDTMP kits, label them with 177 Lu, quality control and in-vitro stability studies. This paper presents some research results on the optimal conditions for labeling EDTMP kit with Lu-177 of low specific activity that was produced on the IVV-9 reactor at the Nuclear Research Institute. (author)

IER-297 CED-2: Final Design for Thermal/Epithermal eXperiments with Jemima Plates with Polyethylene and Hafnium

Energy Technology Data Exchange (ETDEWEB)

Nelson, A. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Percher, C. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Zywiec, W. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Heinrichs, D. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2018-01-11

This report presents the final design (CED-2) for IER-297, and focuses on 15 critical configurations using highly enriched uranium (HEU) Jemima plates moderated by polyethylene with and without hafnium diluent. The goal of the U.S. Nuclear Criticality Safety Program’s Thermal/Epithermal eXperiments (TEX) is to design and conduct new critical experiments to address high priority nuclear data needs from the nuclear criticality safety and nuclear data communities, with special emphasis on intermediate energy (0.625 eV – 100 keV) assemblies that can be easily modified to include various high priority diluent materials. The TEX (IER 184) CED-1 Report [1], completed in 2012, demonstrated the feasibility of meeting the TEX goals with two existing NCSP fissile assets, plutonium Zero Power Physics Reactor (ZPPR) plates and highly enriched uranium (HEU) Jemima plates. The first set of TEX experiments will focus on using the plutonium ZPPR plates with polyethylene moderator and tantalum diluents.

The in vivo disposition and in vitro transmembrane transport of two model radiometabolites of DOTA-conjugated receptor-specific peptides labelled with (177) Lu.

Science.gov (United States)

Volková, Marie; Mandíková, Jana; Bárta, Pavel; Navrátilová, Lucie; Lázníčková, Alice; Trejtnar, František

2015-01-01

In vivo metabolism of the radiolabelled receptor-specific peptides has been described; however, information regarding the pharmacokinetic behaviour of the degradation products within the body is very scarce. The present study was designed to obtain new knowledge on the disposition and elimination of low-molecular radiometabolites of receptor-specific peptides in the organism and to reveal the potential involvement of selected membrane transport mechanisms in the cellular uptake of radiometabolites, especially in the kidney. The study compared pharmacokinetics of two radiometabolites: a final metabolite of somatostatin analogues, (177)Lu-DOTA-DPhe, and a tripeptide metabolite of (177)Lu-DOTA-minigastrin 11, (177)Lu-DOTA-DGlu-Ala-Tyr. Their pharmacokinetics was compared with that of respective parent (177)Lu-radiopeptide. Both radiometabolites exhibited relative rapid clearing from most body tissues in rats in vivo along with predominant renal excretion. The long-term renal retention of the smaller radiometabolite (177)Lu-DOTA-DPhe was lower than that of (177)Lu-DOTA-DGlu-Ala-Tyr. An uptake of (177)Lu-DOTA-DPhe by human renal influx transporter organic cation transporter 2 was found in vitro in a cellular model. The study brings the first experimental data on the in vivo pharmacokinetics of radiometabolites of receptor-specific somatostatin and gastrin analogues. The found results may indicate a negative correlation between the degree of decomposition of the parent peptide chain and the renal retention of the metabolite. Copyright © 2015 John Wiley & Sons, Ltd.

5 CFR 177.102 - Administrative claim; when presented; appropriate OPM office.

Science.gov (United States)

2010-01-01

... SERVICE REGULATIONS ADMINISTRATIVE CLAIMS UNDER THE FEDERAL TORT CLAIMS ACT § 177.102 Administrative claim... have occurred as a result of the incident. (b) All claims filed under the Federal Tort Claims Act as a result of the alleged negligence or wrongdoing of OPM or its employees will be mailed or delivered to the...

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors.

Science.gov (United States)

Brabander, Tessa; van der Zwan, Wouter A; Teunissen, Jaap J M; Kam, Boen L R; Feelders, Richard A; de Herder, Wouter W; van Eijck, Casper H J; Franssen, Gaston J H; Krenning, Eric P; Kwekkeboom, Dik J

2017-08-15

Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy. Experimental Design: For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) 177 Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq) 177 Lu-DOTATATE before 2013 was further analyzed for efficacy and survival. Results: The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred. Conclusions: PRRT with 177 Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with 177 Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. Clin Cancer Res; 23(16); 4617-24. ©2017 AACR . ©2017 American Association for Cancer Research.

Comparative study on DOTA-derivatized bombesin analog labeled with 90Y and 177Lu: in vitro and in vivo evaluation

International Nuclear Information System (INIS)

Koumarianou, Eftychia; Mikolajczak, Renata; Pawlak, Dariusz; Zikos, Xhristos; Bouziotis, Pinelopi; Garnuszek, Piotr; Karczmarczyk, Urszula; Maurin, Michal; Archimandritis, Spyridon C.

2009-01-01

Introduction: The aim of the study was to compare in vitro and in vivo a novel DOTA-chelated bombesin (BN) analog of the amino acid sequence, QRLGNQWAVGHLM-CONH 2 (BN[2-14]NH 2 ), labeled with 90 Y and 177 Lu, for its potential use in targeted radiotherapy of tumors expressing gastrin releasing peptide (GRP) receptors. The same amino acid sequence, but with different chelator, referred as BN1.1 (Gly-Gly-Cys-Aca-QRLGNQWAVGHLM-CONH 2 ), has already been studied and reported; however, the DOTA-chelated one, suitable for labeling with M +3 type radiometals, was not yet described. Methods: The conditions for labeling of DOTA-BN[2-14]NH 2 with noncarrier added 90 Y and with 177 Lu [specific activity (SA), 15 Ci/mg Lu] were investigated and optimized to provide 90 Y-DOTA-BN[2-14]NH 2 and 177 Lu-DOTA-BN[2-14]NH 2 of high SA. The stability of the radiolabeled compounds in human serum was evaluated over a period of 24 h. The human prostate cancer cell line PC-3, known to express GRP receptors, was used for in vitro evaluation of radiolabeled peptide affinity to GRP receptors and for assessment of cytotoxicity of both nonlabeled and radiolabeled peptide. Biodistribution accompanied by receptor blocking was studied in normal Swiss mice. Results: 90 Y-DOTA-BN[2-14]NH 2 and 177 Lu-DOTA-BN[2-14]NH 2 were obtained with radiochemical yield >98% and high SA (67.3 GBq 90 Y/μmol and 33.6 GBq 177 Lu/μmol, respectively). They were stable when incubated in human serum for up to 24 h. The binding affinities of DOTA-BN[2-14]NH 2 and both nat Y- and nat Lu-labeled analogs to GRP receptors were high (IC 50 =1.78, 1.99, and 1.34 nM, respectively), especially for the nat Lu-DOTA-BN[2-14]NH 2 complex. The cytotoxicity study of DOTA-BN[2-14]NH 2 to PC-3 cells revealed an IC 50 =6300 nM after 72 h of exposition, while the labeled derivatives showed no significant cytotoxic effect. The internalization rate to PC-3 cells was more rapid for 177 Lu-labeled peptide (84.87%) than for the 90 Y

Direct measurement of the inelastic neutron acceleration by 177mLu

Directory of Open Access Journals (Sweden)

Menelle A.

2010-03-01

Full Text Available The inelastic neutron acceleration (INNA cross section on the long-lived isomer state of 177mLu has been measured from a new isomeric target using a direct method. The detection of high energy neutrons has been performed using a specially designed setup and a cold neutron beam at the ORPHEE reactor facility in Saclay.

Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

Energy Technology Data Exchange (ETDEWEB)

Rodriguez C, J.; Murphy, C.A. de; Pedraza L, M. [Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, 14000 Mexico D.F. (Mexico); Ferro F, G. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, 06000 Mexico D.F. (Mexico)

2006-07-01

Malignant pancreas tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses after administration of {sup 177}Lu-DOTA-TATE in mice as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (n=18) to obtain the {sup 177}Lu-DOTA-TATE biokinetics and dosimetry. To estimate its therapeutic efficacy 87 MBq were injected in a tail vein of 3 mice and 19 days p.i. there were a partial relapse. There was an epithelial and sarcoma mixed tumour in the kidneys of mouse III. The absorbed dose to tumour, kidney and pancreas was 50.5 {+-} 7.2 Gy, 17.5 {+-} 2.5 Gy and 12.6 {+-} 2.3 Gy respectively. These studies justify further therapeutic and dosimetry estimations to ensure that {sup 177}Lu-DOTA-TATE will act as expected in man considering its kidney radiotoxicity. (Author)

EVALUATION OF PRECIPITATION HARDENING HEAT TREATMENT OF PH 17-7 STAINLESS STEEL SPRING

Directory of Open Access Journals (Sweden)

A. A. Babakoohi Ashrafi

2016-06-01

Full Text Available In this paper, the influence of heat treatment on PH17-7 stainless steel spring was evaluated. Precipitation hardening phenomenon of  PH 17-7 steel was evaluated in three stages. First, the spring constant changes with time and temperature was evaluated. Second, the spring constant changes with respect to its original length at constant temperature and time with blocking (spring length after compression, 18 and 21 mm were investigated.  And finally, the spring heat treatment at 480 °C for 80 min and then holding at 230 °C in oil bath for 60 min without blocking were investigated. The results showed that the use of 18 mm block have large spring constant than 21 mm block. The optimal conditions (480°C for 80 min for this spring to reaching maximum spring constant were determined.

21 CFR 177.1345 - Ethylene/1,3-phenylene oxyethylene isophthalate/ terephthalate copolymer.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Ethylene/1,3-phenylene oxyethylene isophthalate... Ethylene/1,3-phenylene oxyethylene isophthalate/ terephthalate copolymer. Ethylene/1, 3-phenylene... polymers complying with § 177.1630. (a) Identity. For the purpose of this section, ethylene/1,3-phenylene...

21 CFR 177.1010 - Acrylic and modified acrylic plastics, semirigid and rigid.

Science.gov (United States)

2010-04-01

... than 15 percent alcohol. Phenyl salicylate. (6) Release agents: Fatty acids derived from animal and vegetable fats and oils, and fatty alcohols derived from such acids. (7) Surface active agent: Sodium...: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.1010...

Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

International Nuclear Information System (INIS)

Escudero-Castellanos, Alondra; Universidad Autonoma del Estado de Mexico, Toluca, Estado de Mexico; Ocampo-Garcia, B.E.; Ferro-Flores, Guillermina; Santos-Cuevas, C.L.; Isaac-Olive, Keila; Olmos-Ortiz, Andrea; Garcia-Quiroz, Janice; Garcia-Becerra, Rocio; Diaz, Lorenza

2017-01-01

This study aimed to synthesize a new 177 Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and α(v) β(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and α(v)β(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177 Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical. (author)

Targeted radionuclide therapy with A 177Lu-labeled anti-HER2 nanobody.

Science.gov (United States)

D'Huyvetter, Matthias; Vincke, Cécile; Xavier, Catarina; Aerts, An; Impens, Nathalie; Baatout, Sarah; De Raeve, Hendrik; Muyldermans, Serge; Caveliers, Vicky; Devoogdt, Nick; Lahoutte, Tony

2014-01-01

RIT has become an attractive strategy in cancer treatment, but still faces important drawbacks due to poor tumor penetration and undesirable pharmacokinetics of the targeting vehicles. Smaller radiolabeled antibody fragments and peptides feature highly specific target accumulation, resulting in low accumulation in healthy tissue, except for the kidneys. Nanobodies are the smallest (MWnanobodies is predominantly dictated by the number of polar residues in the C-terminal amino acid tag. Three nanobodies were produced with different C-terminal amino-acid tag sequences (Myc-His-tagged, His-tagged, and untagged). Dynamic planar imaging of Wistar rats with 111In-DTPA-nanobodies revealed that untagged nanobodies showed a 70% drop in kidney accumulation compared to Myc-His-tagged nanobodies at 50 min p.i.. In addition, coinfusion of untagged nanobodies with the plasma expander Gelofusin led to a final reduction of 90%. Similar findings were obtained with different 177Lu-DTPA-2Rs15d nanobody constructs in HER2pos tumor xenografted mice at 1 h p.i.. Kidney accumulation decreased 88% when comparing Myc-His-tagged to untagged 2Rs15d nanobody, and 95% with a coinfusion of Gelofusin, without affecting the tumor targeting capacity. Consequently, we identified a generic method to reduce kidney retention of radiolabeled nanobodies. Dosimetry calculations of Gelofusin-coinfused, untagged 177Lu-DTPA-2Rs15d revealed a dose of 0.90 Gy/MBq that was delivered to both tumor and kidneys and extremely low doses to healthy tissues. In a comparative study, 177Lu-DTPA-Trastuzumab supplied 6 times more radiation to the tumor than untagged 177Lu-DTPA-2Rs15d, but concomitantly also a 155, 34, 80, 26 and 4180 fold higher radioactivity burden to lung, liver, spleen, bone and blood. Most importantly, nanobody-based targeted radionuclide therapy in mice bearing small estiblashed HER2pos tumors led to an almost complete blockade of tumor growth and a significant difference in event-free survival

Development of a lyophilized formulation for preparing the radiopharmaceutical 177Lu-DOTA-Anti-CD20

International Nuclear Information System (INIS)

Serrano E, L. A.

2015-01-01

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. 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 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 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 177 Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

Improved DC performance of AlGaN/GaN high electron mobility transistors using hafnium oxide for surface passivation

International Nuclear Information System (INIS)

Liu, Chang; Chor, Eng Fong; Tan, Leng Seow

2007-01-01

Improved DC performance of AlGaN/GaN high electron mobility transistors (HEMTs) have been demonstrated using reactive-sputtered hafnium oxide (HfO 2 ) thin film as the surface passivation layer. Hall data indicate a significant increase in the product of sheet carrier concentration (n s ) and electron mobility (μ n ) in the HfO 2 -passivated HEMTs, compared to the unpassivated HEMTs. This improvement in electron carrier characteristics gives rise to a 22% higher I Dmax and an 18% higher g mmax in HEMTs with HfO 2 passivation relative to the unpassivated devices. On the other hand, I gleak of the HEMTs decreases by nearly one order of magnitude when HfO 2 passivation is applied. In addition, drain current is measured in the subthreshold regime. Compared to the unpassivated HEMTs, HfO 2 -passivated HEMTs exhibit a much smaller off-state I D , indicating better turn-off characteristics

Synergistic anti-cancer response to chemotherapy and 177Lu-labelled APOMABR radioimmunotherapy in a preclinical model of lung cancer

International Nuclear Information System (INIS)

Staudacher, A.H.; Brown, M.P.

2015-01-01

Full text of publication follows. Aim: We have identified a murine monoclonal antibody (APOMAB R ) which targets the La antigen. La is a ribonucleoprotein which is over-expressed in malignancy and is only accessible to antibody binding when tumour cells die, making APOMAB R a dead tumour cell-specific marker. We hypothesise that APOMAB R radio-labelled with the β-particle emitting radionuclide Lutetium-177 ( 177 Lu) will be an effective anti-tumour treatment in vivo, particular after chemotherapy, as the targeting of radio-labelled APOMAB R specifically to dead tumour cells within the tumour tissue will result in the surrounding viable tumour cells being irradiated with a therapeutic dose of β-radiation. Material and Methods: The binding of APOMAB R to viable and dead murine Lewis Lung cells (LL2) was examined in vitro by flow cytometry. Subsequently, C57Bl/6 mice bearing syngeneic LL2 tumours were treated with chemotherapy (gemcitabine/cisplatin) and the tumour uptake of biotinylated APOMAB R was determined. We then administered escalating activities of 177 Lu-labelled APOMAB R or a 177 Lu-labelled iso-type control antibody either alone or 24 hours after chemotherapy and monitored tumour growth and survival. We also analysed the bio-distribution of 177 Lu-labelled APOMAB R in LL2 tumour-bearing mice which had or had not been treated with chemotherapy to determine whether the uptake of APOMAB R after chemotherapy treatment was tumour-specific. Results: In vitro analysis revealed that APOMAB R did not bind viable LL2 cells, but bound with high avidity to cisplatin-treated, dead LL2 cells. Chemotherapy increased tumour cell death in vivo, and was associated with increased tumour uptake of APOMAB R compared to LL2 tumour-bearing mice that did not receive chemotherapy. Administration of escalating doses of 177 Lu-labelled APOMAB R alone to tumour-bearing mice was well tolerated but showed only modest anti-tumour activity which was comparable to the response seen

Protective coatings of hafnium dioxide by atomic layer deposition for microelectromechanical systems applications

Energy Technology Data Exchange (ETDEWEB)

Berdova, Maria, E-mail: maria.berdova@aalto.fi [Aalto University, Department of Materials Science and Engineering, 02150, Espoo (Finland); Wiemer, Claudia; Lamperti, Alessio; Tallarida, Grazia; Cianci, Elena [Laboratorio MDM, IMM CNR, Via C. Olivetti 2, 20864, Agrate Brianza, MB (Italy); Lamagna, Luca; Losa, Stefano; Rossini, Silvia; Somaschini, Roberto; Gioveni, Salvatore [STMicroelectronics, Via C. Olivetti 2, 20864, Agrate Brianza, MB (Italy); Fanciulli, Marco [Laboratorio MDM, IMM CNR, Via C. Olivetti 2, 20864, Agrate Brianza, MB (Italy); Università degli studi di Milano Bicocca, Dipartimento di Scienza dei Materiali, 20126, Milano (Italy); Franssila, Sami, E-mail: sami.franssila@aalto.fi [Aalto University, Department of Materials Science and Engineering, 02150, Espoo (Finland)

2016-04-15

Graphical abstract: - Highlights: • Atomic layer deposition of HfO{sub 2} from (CpMe){sub 2}Hf(OMe)Me or Hf(NMeEt){sub 4} and ozone for potential applications in microelectromechanical systems. • ALD HfO{sub 2} protects aluminum substrates from degradation in moist environment and at the same time retains good reflectance properties of the underlying material. • The resistance of hafnium dioxide to moist environment is independent of chosen precursors. - Abstract: This work presents the investigation of HfO{sub 2} deposited by atomic layer deposition (ALD) from either HfD-CO4 or TEMAHf and ozone for microelectromechanical systems (MEMS) applications, in particular, for environmental protection of aluminum micromirrors. This work shows that HfO{sub 2} films successfully protect aluminum in moist environment and at the same time retain good reflectance properties of underlying material. In our experimental work, the chemical composition, crystal structure, electronic density and roughness of HfO{sub 2} films remained the same after one week of humidity treatment (relative humidity of 85%, 85 °C). The reflectance properties underwent only minor changes. The observed shift in reflectance was only from 80–90% to 76–85% in 400–800 nm spectral range when coated with ALD HfO{sub 2} films grown with Hf(NMeEt){sub 4} and no shift (remained in the range of 68–83%) for films grown from (CpMe){sub 2}Hf(OMe)Me.

In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

International Nuclear Information System (INIS)

Forrer, Flavio; Mueller-Brand, Jan; Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R.; Lohri, Andreas; Moldenhauer, Gerhard

2009-01-01

131 I- and 90 Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time ( 177 Lu or 90 Y. Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10 5 times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m 2 body surface 177 Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of 177 Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with 177 Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. 177 Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL. (orig.)

Preparation and biological evaluation of 111In-, 177Lu- and 90Y-labeled DOTA analogues conjugated to B72.3

International Nuclear Information System (INIS)

Mohsin, Huma; Fitzsimmons, Jonathan; Shelton, Tiffani; Hoffman, Timothy J.; Cutler, Cathy S.; Lewis, Michael R.; Athey, Phillip S.; Gulyas, Gyongyi; Kiefer, Garry E.; Frank, R. Keith; Simon, Jaime; Lever, Susan Z.; Jurisson, Silvia S.

2007-01-01

Three 1,4,7,10-tetraazacyclododecane-N,N',N '' ,N '' '-tetraacetic acid (DOTA) analogues were evaluated for relative in vivo stability when radiolabeled with 111 In, 90 Y and 177 Lu and conjugated to the monoclonal antibody B72.3. The DOTA analogues evaluated were 'NHS-DOTA' [N-hydroxysuccinimdyl (NHS) group activating one carboxylate], 'Arm-DOTA' (also known as MeO-DOTA; with a p-NCS, o-MeO-benzyl moiety on the methylene group of one acetic acid arm) and 'Back-DOTA' (with a p-NCS-benzyl moiety on a backbone methylene group of the macrocycle). The B72.3 was conjugated to the DOTA analogues to increase the retention time of the radioloabeled conjugates in vivo in mice. The serum stability of the various radiometalated DOTA conjugates showed them to have good stability out to 168 h (all >95% except 111 In-NHS-DOTA-B72.3, which was 91% stable). Hydroxyapatite stability for the 111 In and 177 Lu DOTA-conjugates was >95% at 168 h, while the 90 Y DOTA-conjugates were somewhat less stable (between 90% and 95% at 168 h). The biodistribution studies of the radiometalated DOTA-conjugates showed that no significant differences were observed for the 111 In and 177 Lu analogues; however, the 90 Y analogues showed lower stabilities, as evidenced by their increased bone uptake relative to the other two [2-20% injected dose per gram (% ID/g) for 90 Y and 2-8% ID/g for 111 In and 177 Lu]. The lower stability of the 90 Y analogues could be due to the higher beta energy of 90 Y and/or to the larger ionic radius of Y 3+ . Based on the bone uptake observed, the 177 Lu-NHS-DOTA-B72.3 had slightly lower stability than the 177 Lu-Arm-DOTA-B72.3 and 177 Lu-Back-DOTA-B72.3, but not significantly at all time points. For 90 Y, the analogue showing the lowest stability based on bone uptake was 90 Y-Arm-DOTA-B72.3, perhaps because of the metal's larger ionic radius and potential steric interactions minimizing effective complexation. The 111 In analogues all showed similar biological

Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

International Nuclear Information System (INIS)

Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane; Dorrer, Holger; Zhernosekov, Konstantin; Koester, Ulli; Tuerler, Andreas; Schibli, Roger

2014-01-01

The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with 67 Cu- and 177 Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide 177 Lu and the potential alternative 161 Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched 160 Gd targets. 161 Tb and 177 Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of 177 Lu- and 161 Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. 177 Lu- and 161 Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. 161 Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the 177 Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the 161 Tb-DOTA-chCE7 than the 177 Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM 161 Tb RIT is more effective compared to 177 Lu RIT in ovarian cancer xenografts. These results suggest that 161 Tb is a promising candidate for future clinical

19 CFR 177.7 - Situations in which no ruling will be issued.

Science.gov (United States)

2010-04-01

....7 Section 177.7 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... for a ruling which fails to comply with the provisions of this part. Moreover, no ruling letter will... litigation in the United States Court of International Trade. No ruling letter will be issued with respect to...

Targeted radiotherapy with 177 Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

International Nuclear Information System (INIS)

Murphy, M. A de; Pedraza L, M.; Rodriguez C, J.; Ferro F, G.; Murphy S, E.

2006-01-01

Malignant pancreas tumours induced in athymic mice are a good model for targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses and to evaluate 177 Lu-DOTA-TATE as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells, which over-express somatostatin receptors, were injected in athymic mice and 20 days later the mean tumour size was 3.08 square cm (n=3). A mean of 86.3 MBq 177 Lu-DOTA-TATE, was injected in a tail vein and 19 days after therapy the size of the tumours was 0.81 square cm. There was a partial relapse and after 16 days, when sacrificed, the mean tumour size was 8.28 cubic cm. An epithelial and sarcoma mixed tumour in the kidney of one treated mouse was found. The tumour of the control mouse was 8.61 cubic cm when sacrificed 14 days after tumour induction. Radiotherapy estimates to the tumours was 35.9-39.7 Gy and the tumours might have been completely reduced with a second therapy dose. These preliminary studies justify further therapeutic and dosimetry estimations to ensure that Lu- 177 -DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

Biokinetics and dosimetry with 177Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

Science.gov (United States)

Rodríguez-Cortés, J.; de Murphy, C. Arteaga; Ferro-Flores, Ge; Pedraza-López, M.; Murphy-Stack, E.

Malignant pancreatic tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to determine biokinetic parameters in mice, in order to estimate the induced pancreatic tumour absorbed doses and to evaluate an `in house' 177Lu-DOTA-TATE radiopharmaceutical as part of preclinical studies for targeted therapy in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (nD22) to obtain biokinetic and dosimetric data of 177Lu-DOTA-TATE. The mean tumour uptake 2 h post injection was 14.76±1.9% I.A./g; kidney and pancreas uptake, at the same time, were 7.27±1.1% I.A./g (1.71±0.90%/organ) and 4.20±0.98% I.A./g (0.42±0.03%/organ), respectively. The mean absorbed dose to tumour, kidney and pancreas was 0.58±0.02 Gy/MBq; 0.23±0.01 Gy/MBq and 0.14±0.01 Gy/MBq, respectively. These studies justify further dosimetric estimations to ensure that 177Lu-DOTA-TATE will act as expected in humans.

Report on the 1. research coordination meeting on 'Development of therapeutic radiopharmaceuticals based on {sup 177}Lu for radionuclide therapy'

Energy Technology Data Exchange (ETDEWEB)

NONE

2006-07-01

Radionuclide therapy (RNT) employing radiopharmaceuticals labelled with emitting radionuclides is fast emerging as an important part of nuclear medicine. Radionuclide therapy is effectively utilized for bone pain palliation, thus providing significant improvement in quality of life of patients suffering from pain resulting from bone metastasis. Targeting primary diseases by using specific carrier molecules labelled with radionuclides is also widely investigated and efficacious products have been emerging for the treatment of Lymphoma and Neuroendocrine tumours. In order to ensure the wider use of radiopharmaceuticals, it is essential to carefully consider the choice of radionuclides that together with the carrier molecules will give suitable pharmacokinetic properties and therapeutic efficacy. The criteria for the selection of a radionuclide for radiotherapy are suitable decay characteristics and amenable chemistry. However, the practical considerations in selecting a radionuclide for targeted therapy are availability in high radionuclidic purity as well as high specific activity and low production cost and comfortable delivery logistics. {sup 177}Lu is one of the isotopes emerging as a clear choice for therapy. Worldwide, the isotope is under investigation for approximately 30 different clinical applications, including treatment of colon cancer, metastatic bone cancer, non-Hodgkin's lymphoma, and lung cancer. {sup 177}Lu decays with a half-life of 6.71 d by emission of particles with E{sub max} of 497 keV (78.6%), 384 keV (9.1%) and 176 keV (12.2%). It also emits photons of 113 keV (6.4%) and 208 keV (11%), that are ideally suited for imaging the in-vivo localization and dosimetric calculations applying a gamma camera. The physical half-life of {sup 177}Lu is comparable to that of {sup 131}I, the most widely used therapeutic radionuclide. The long halflife of {sup 177}Lu provides logistic advantage for production, QA/QC of the products as well as feasibility to

Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy

Energy Technology Data Exchange (ETDEWEB)

Seregni, E.; Maccauro, M.; Chiesa, C.; Pascali, C.; Lorenzoni, A.; Bogni, A.; Coliva, A.; Bombardieri, E. [Fondazione IRCCS Istituto Nazionale Tumori, Nuclear Medicine, Milan (Italy); Mariani, L.; Vullo, S.Lo [Fondazione IRCCS Istituto Nazionale Tumori, Statistics and Biometry Unit, Milan (Italy); Mazzaferro, V. [Fondazione IRCCS Istituto Nazionale Tumori, Surgery and Liver Transplantation, Milan (Italy); De Braud, F.; Buzzoni, R. [Fondazione IRCCS Istituto Nazionale Tumori, Medical Oncology, Milan (Italy); Milione, M. [Fondazione IRCCS Istituto Nazionale Tumori, Pathology Department, Milan (Italy)

2014-02-15

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ({sup 90}Y) and a medium-energy beta/gamma emitter ({sup 177}Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [{sup 177}Lu]DOTA-TATE (5.55 GBq) and [{sup 90}Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [{sup 177}Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment The results of our study indicates that combined [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. (orig.)

Efficient UV-emitting X-ray phosphors: octahedral Zr(PO4)6 luminescence centers in potassium hafnium-zirconium phosphates K2Hf1-xZrx(PO4)2 and KHf2(1-x)Zr2x(PO4)3

International Nuclear Information System (INIS)

Torardi, C.C.; Miao, C.R.; Li, J.

2003-01-01

Potassium hafnium-zirconium phosphates, K 2 Hf 1-x Zr x (PO 4 ) 2 and KHf 2(1-x) Zr 2x (PO 4 ) 3 , are broad-band UV-emitting phosphors. At room temperature, they have emission peak maxima at approximately 322 and 305 nm, respectively, under 30 kV peak molybdenum X-ray excitation. Both phosphors demonstrate luminescence efficiencies that make them up to ∼60% as bright as commercially available CaWO 4 Hi-Plus. The solid-state and flux synthesis conditions, and X-ray excited UV luminescence of these two phosphors are discussed. Even though the two compounds have different atomic structures, they contain zirconium in the same active luminescence environment as that found in highly efficient UV-emitting BaHf 1-x Zr x (PO 4 ) 2 . All the three materials have hafnium and zirconium in octahedral coordination via oxygen-atom corner sharing with six separate PO 4 tetrahedra. This octahedral Zr(PO 4 ) 6 moiety appears to be an important structural element for efficient X-ray excited luminescence, as are the edge-sharing octahedral TaO 6 chains for tantalate emission

Encapsulation of a radiolabeled cluster inside a fullerene cage, (177)Lu(x)Lu((3-x))N@C(80): an interleukin-13-conjugated radiolabeled metallofullerene platform.

Science.gov (United States)

Shultz, Michael D; Duchamp, James C; Wilson, John D; Shu, Chun-Ying; Ge, Jiechao; Zhang, Jianyuan; Gibson, Harry W; Fillmore, Helen L; Hirsch, Jerry I; Dorn, Harry C; Fatouros, Panos P

2010-04-14

In this communication, we describe the successful encapsulation of (177)Lu into the endohedral metallofullerene (177)Lu(x)Lu(3-x)N@C(80) (x = 1-3) starting with (177)LuCl(3) in a modified quartz Kraschmer-Huffman electric generator. We demonstrate that the (177)Lu (beta-emitter) in this fullerene cage is not significantly released for a period of up to at least one-half-life (6.7 days). We also demonstrate that this agent can be conjugated with an interleukin-13 peptide that is designed to target an overexpressed receptor in glioblastoma multiforme tumors. This nanoparticle delivery platform provides flexibility for a wide range of radiotherapeutic and radiodiagnostic multimodal applications.

Lu-177-PSMA-617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients with Castration-Resistant Prostate Cancer: Stability, Bio-distribution and Dosimetry

Directory of Open Access Journals (Sweden)

Levent Kabasakal

2017-06-01

Full Text Available Objective: The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177 prostate-specific membrane antigen (PSMA-617. Methods: For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h. The stability was also calculated in blood and urine samples. Post-therapeutic dosimetry was performed based on whole body and single photon emission computed tomography/computed tomography (SPECT/CT scans on dual-headed SPECT/CT system. Results: The radiochemical yield of Lu-177-PSMA-617 was >99%. It remained stable in saline up to 48 h. Analyses of the blood and urine samples showed a single radioactivity peak even at 24 hours after injection. Half-life of the distribution and elimination phases were calculated to be 0.16±0.09 and 10.8±2.5 hours, respectively. The mean excretion rate was 56.5±8.8% ranging from 41.5% to 65.4% at 24 h. Highest radiation estimated doses were calculated for parotid glands and kidneys (1.90±1.19 and 0.82±0.25 Gy/GBq respectively. Radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p<0.05 (0.030±0.008 Gy/GBq. Conclusion: Lu-177-PSMA-617 is a highly stable compound both in vitro and in vivo. Lu-177-PSMA-617 therapy seems to be a safe method for the treatment of castration-resistant prostate cancer patients. The fractionation regime that enables the longest duration of tumor control and/or survival will have to be developed in further studies.

Absolute El Transition Probabilities in the Deformed Nuclei 177Yb and Hf179

International Nuclear Information System (INIS)

Malmskog, Sven G.

1964-08-01

The absolute E1-transition probabilities have been measured for two 7/2 - (514) levels populated from the short-lived isomers 177m Yb (6.4 sec) and 179m Hf (18.6 sec), a delayed coincidence set up being used for the purpose. This gave a half life of T 1/2 = (4.48 ± 0.08)x10 -9 sec for the 104 keV level in 177 Yb and T 1/2 = (1.86 ± 0.05)x10 -9 sec for the 217 keV level in 179 Hf. The result has been compared with the calculations made by Nilsson. The effect of the pairing correlation has also been taken into account. An agreement with the experimental values to within a factor of three is obtained. An extrapolated estimate of the half life for the 408.9 keV 7/2 - (514) level in 181 W gives 3x10 -11 sec

Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

Directory of Open Access Journals (Sweden)

Johnnie J Orozco

Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

Energy Technology Data Exchange (ETDEWEB)

Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC, Department of Pathology, Rotterdam (Netherlands)

2007-05-15

In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Male Lewis rats were injected with 278 or 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of {sup 99m}Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of {sup 99m}Tc-DMSA SPECT scintigrams at 130 days after [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate therapy correlated well with 1/creatinine (r {sup 2} = 0.772, p < 0.001). Amifostine and lysine effectively decreased functional renal damage caused by high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well

The magnetic properties of $^{\\rm 177}$Hf and $^{\\rm 180}$Hf in the strong coupling deformed model

OpenAIRE

Muto, S.; Stone, N. J.; Bingham, C. R.; Stone, J. R.; Walker, P. M.; Audi, G.; Gaulard, C.; Köster, U.; Nikolov, J.; Nishimura, K.; Ohtsubo, T.; Podolyak, Z.; Risegari, L.; Simpson, G. S.; Veskovic, M.

2014-01-01

This paper reports NMR measurements of the magnetic dipole moments of two high-K isomers, the 37/2$^-$, 51.4 m, 2740 keV state in $^{\\rm 177}$Hf and the 8$^-$, 5.5 h, 1142 keV state in $^{\\rm 180}$Hf by the method of on-line nuclear orientation. Also included are results on the angular distributions of gamma transitions in the decay of the $^{\\rm 177}$Hf isotope. These yield high precision E2/M1 multipole mixing ratios for transitions in bands built on the 23/2$^+$, 1.1 s, isomer at 1315 keV ...

Comparative study on DOTA-derivatized bombesin analog labeled with {sup 90}Y and {sup 177}Lu: in vitro and in vivo evaluation

Energy Technology Data Exchange (ETDEWEB)

Koumarianou, Eftychia [Institute R-RP, NCSR ' Demokritos' , Athens (Greece); IAE, Radioisotope Centre POLATOM, 05-400 Swierk-Otwock (Poland)], E-mail: eytyxiak@yahoo.com; Mikolajczak, Renata; Pawlak, Dariusz [IAE, Radioisotope Centre POLATOM, 05-400 Swierk-Otwock (Poland); Zikos, Xhristos; Bouziotis, Pinelopi [Institute R-RP, NCSR ' Demokritos' , Athens (Greece); Garnuszek, Piotr; Karczmarczyk, Urszula; Maurin, Michal [Department of Radiopharmaceuticals, National Medicines Institute, Chelmska 30/34, 00-725 Warsaw (Poland); Archimandritis, Spyridon C. [Institute R-RP, NCSR ' Demokritos' , Athens (Greece)

2009-08-15

Introduction: The aim of the study was to compare in vitro and in vivo a novel DOTA-chelated bombesin (BN) analog of the amino acid sequence, QRLGNQWAVGHLM-CONH{sub 2} (BN[2-14]NH{sub 2}), labeled with {sup 90}Y and {sup 177}Lu, for its potential use in targeted radiotherapy of tumors expressing gastrin releasing peptide (GRP) receptors. The same amino acid sequence, but with different chelator, referred as BN1.1 (Gly-Gly-Cys-Aca-QRLGNQWAVGHLM-CONH{sub 2}), has already been studied and reported; however, the DOTA-chelated one, suitable for labeling with M{sup +3} type radiometals, was not yet described. Methods: The conditions for labeling of DOTA-BN[2-14]NH{sub 2} with noncarrier added {sup 90}Y and with {sup 177}Lu [specific activity (SA), 15 Ci/mg Lu] were investigated and optimized to provide {sup 90}Y-DOTA-BN[2-14]NH{sub 2} and {sup 177}Lu-DOTA-BN[2-14]NH{sub 2} of high SA. The stability of the radiolabeled compounds in human serum was evaluated over a period of 24 h. The human prostate cancer cell line PC-3, known to express GRP receptors, was used for in vitro evaluation of radiolabeled peptide affinity to GRP receptors and for assessment of cytotoxicity of both nonlabeled and radiolabeled peptide. Biodistribution accompanied by receptor blocking was studied in normal Swiss mice. Results: {sup 90}Y-DOTA-BN[2-14]NH{sub 2} and {sup 177}Lu-DOTA-BN[2-14]NH{sub 2} were obtained with radiochemical yield >98% and high SA (67.3 GBq {sup 90}Y/{mu}mol and 33.6 GBq {sup 177}Lu/{mu}mol, respectively). They were stable when incubated in human serum for up to 24 h. The binding affinities of DOTA-BN[2-14]NH{sub 2} and both {sup nat}Y- and {sup nat}Lu-labeled analogs to GRP receptors were high (IC{sub 50}=1.78, 1.99, and 1.34 nM, respectively), especially for the {sup nat}Lu-DOTA-BN[2-14]NH{sub 2} complex. The cytotoxicity study of DOTA-BN[2-14]NH{sub 2} to PC-3 cells revealed an IC{sub 50}=6300 nM after 72 h of exposition, while the labeled derivatives showed no

Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

Energy Technology Data Exchange (ETDEWEB)

Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Zhernosekov, Konstantin [ITG Isotope Technologies Garching GmbH, Garching (Germany); Koester, Ulli [Institut Laue-Langevin, Grenoble (France); Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Department of Chemistry and Biochemistry, Berne (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

2014-10-15

The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with {sup 67}Cu- and {sup 177}Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide {sup 177}Lu and the potential alternative {sup 161}Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched {sup 160}Gd targets. {sup 161}Tb and {sup 177}Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. {sup 161}Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the {sup 177}Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the {sup 161}Tb-DOTA-chCE7 than the {sup 177}Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM {sup 161}Tb RIT is more effective compared to {sup 177}Lu RIT in ovarian cancer xenografts

Direct in vitro and in vivo comparison of {sup 161}Tb and {sup 177}Lu using a tumour-targeting folate conjugate

Energy Technology Data Exchange (ETDEWEB)

Mueller, Cristina; Reber, Josefine; Haller, Stephanie [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger; Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry, Bern (Switzerland); Bernhardt, Peter [The Sahlgrenska Academy, University of Gothenburg, Department of Radiation Physics, Gothenburg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengeneering, Gothenburg (Sweden); Zhernosekov, Konstantin [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

2014-03-15

The radiolanthanide {sup 161}Tb (T{sub 1/2} = 6.90 days, Eβ{sup -}{sub av} = 154 keV) was recently proposed as a potential alternative to {sup 177}Lu (T{sub 1/2} = 6.71 days, Eβ{sup -}{sub av} = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare {sup 161}Tb and {sup 177}Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). {sup 161}Tb-cm09 and {sup 177}Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo {sup 161}Tb-cm09 and {sup 177}Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using {sup 99m}Tc-dimercaptosuccinic acid (DMSA). To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for {sup 161}Tb-cm09 (IC{sub 50} ∝0.014 MBq/ml and ∝2.53 MBq/ml) compared to {sup 177}Lu-cm09 (IC{sub 50} ∝0.063 MBq/ml and ∝4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies {sup 161}Tb-cm09 reduced tumour growth more efficiently than {sup 177}Lu-cm09. These findings were in line with the higher absorbed tumour dose for {sup 161}Tb-cm09 (3.3 Gy/MBq) compared to {sup 177}Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates. Compared to {sup 177}Lu-cm09 we demonstrated equal imaging

Long-term toxicity of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate in rats

Energy Technology Data Exchange (ETDEWEB)

Rolleman, Edgar J.; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Bijster, Magda; Jong, Marion de [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Visser, Theo J. [Erasmus MC Rotterdam, Department of Internal Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC Rotterdam, Department of Pathology, Rotterdam (Netherlands); Lindemans, Jan [Erasmus MC Rotterdam, Department of Clinical Chemistry, Rotterdam (Netherlands)

2007-02-15

Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models. Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine levels rose significantly after 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores were maximal after 555 MBq and significantly lower in the 278 and 2 x 278 MBq groups. Three doses of 185 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469{+-}18, 134{+-}70 and 65{+-}15 {mu}mol/l, respectively; p<0.001). Renal histological damage scores were not significantly influenced by dose fractionation. Lysine co-administration with three weekly treatments of 185 MBq significantly lowered serum creatinine and proteinuria. Injection of high doses of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage. (orig.)

Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with {sup 177}Lu and evaluation in vitro and in vivo stability; Radiomarcado del peptido c-DOTA-RGD y c-DOTA-RGDf con {sup 177}Lu y evaluacion de su estabilidad in vitro e in vivo

Energy Technology Data Exchange (ETDEWEB)

Vilchis J, A.

2010-07-01

Integrin {alpha}v{beta}3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the {alpha}v{beta}3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with {sup 177}Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of {sup 177}LuCl{sub 3} with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90{sup o} C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive {alpha}v{beta}3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. {sup 177}Lu-DOTA-RGD and {sup 177}Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to {open_square}{sub v}{open_square}{sub 3} receptors. (Author)

In vitro characterization of {sup 177}Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

Energy Technology Data Exchange (ETDEWEB)

Forrer, Flavio; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Lohri, Andreas [Basel University Medical Clinic, Liestal (Switzerland); Moldenhauer, Gerhard [German Cancer Research Center, Division of Molecular Immunology, Heidelberg (Germany)

2009-09-15

{sup 131}I- and {sup 90}Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (<20 min) with either {sup 177}Lu or {sup 90}Y. Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10{sup 5} times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m{sup 2} body surface {sup 177}Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of {sup 177}Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with {sup 177}Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. {sup 177}Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL. (orig.)

Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

Science.gov (United States)

Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J H; Newman, Debra K; Newman, Peter J; Santoso, Sentot

2010-04-01

The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner.

The challenges of treating paraganglioma patients with 177Lu-DOTATATE PRRT: Catecholamine crises, tumor lysis syndrome and the need for modification of treatment protocols

International Nuclear Information System (INIS)

Makis, William; Mccann, Karey; Mcewan, Alexander J. B.

2015-01-01

A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted radioisotope therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with 177 Lu-[DOTA0,Tyr3]octreotate (DOTATATE) radioisotope therapy using established protocols. Three paraganglioma patients were treated with 4–5 cycles of 177 Lu-DOTATATE and were evaluated for side effects and response to therapy. Two of the three patients developed severe adverse reactions following their first 177 Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2–4 h and by reducing the administered dose of 177 Lu-DOTATATE. Subsequent 177 Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to therapy was achieved in all three patients, resulting in significantly improved quality of life. 177 Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions

Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

Energy Technology Data Exchange (ETDEWEB)

Murphy, M. A de; Pedraza L, M. [Department of Nuclear Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Rodriguez C, J. [Faculty of Medicine, UAEM, Toluca, Estado de Mexico (Mexico); Ferro F, G. [ININ, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, Mexico D.F. (Mexico)

2006-07-01

Malignant pancreas tumours induced in athymic mice are a good model for targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses and to evaluate {sup 177}Lu-DOTA-TATE as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells, which over-express somatostatin receptors, were injected in athymic mice and 20 days later the mean tumour size was 3.08 square cm (n=3). A mean of 86.3 MBq {sup 177}Lu-DOTA-TATE, was injected in a tail vein and 19 days after therapy the size of the tumours was 0.81 square cm. There was a partial relapse and after 16 days, when sacrificed, the mean tumour size was 8.28 cubic cm. An epithelial and sarcoma mixed tumour in the kidney of one treated mouse was found. The tumour of the control mouse was 8.61 cubic cm when sacrificed 14 days after tumour induction. Radiotherapy estimates to the tumours was 35.9-39.7 Gy and the tumours might have been completely reduced with a second therapy dose. These preliminary studies justify further therapeutic and dosimetry estimations to ensure that Lu-{sup 177}-DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

Magnetic properties of Hf177 and Hf180 in the strong-coupling deformed model

Science.gov (United States)

Muto, S.; Stone, N. J.; Bingham, C. R.; Stone, J. R.; Walker, P. M.; Audi, G.; Gaulard, C.; Köster, U.; Nikolov, J.; Nishimura, K.; Ohtsubo, T.; Podolyak, Z.; Risegari, L.; Simpson, G. S.; Veskovic, M.; Walters, W. B.

2014-04-01

This paper reports NMR measurements of the magnetic dipole moments of two high-K isomers, the 37/2-, 51.4 m, 2740 keV state in Hf177 and the 8-, 5.5 h, 1142 keV state in Hf180 by the method of on-line nuclear orientation. Also included are results on the angular distributions of γ transitions in the decay of the Hf177 isotope. These yield high precision E2/M1 multipole mixing ratios for transitions in bands built on the 23/2+, 1.1 s, isomer at 1315 keV and on the 9/2+, 0.663 ns, isomer at 321 keV. The new results are discussed in the light of the recently reported finding of systematic dependence of the behavior of the gR parameter upon the quasiproton and quasineutron make up of high-K isomeric states in this region.

Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with 177Lu and evaluation in vitro and in vivo stability

International Nuclear Information System (INIS)

Vilchis J, A.

2010-01-01

Integrin αvβ3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the αvβ3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with 177 Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of 177 LuCl 3 with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90 o C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive αvβ3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. 177 Lu-DOTA-RGD and 177 Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to □ v □ 3 receptors. (Author)

Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

Directory of Open Access Journals (Sweden)

Kwon Joong Yong

2016-05-01

Full Text Available Radiolabeled antibodies (mAbs provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day a suitable radionuclide for radioimmunotherapy (RIT of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB, caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease.

Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

Science.gov (United States)

Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

2015-01-01

Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

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

DEFF Research Database (Denmark)

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

2014-01-01

for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon...... carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96....... The rats suffered from reversible myelotoxicity after treatment. CONCLUSIONS: Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect....

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

National Research Council Canada - National Science Library

Vallabhajosula, Shankar

2007-01-01

Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination With Docetaxel

National Research Council Canada - National Science Library

Vallabhajosula, Shankar

2006-01-01

Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

Energy Technology Data Exchange (ETDEWEB)

Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

2016-03-15

Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

Somatostatin-receptor-targeted α-emitting 213Bi is therapeutically more effective than β--emitting 177Lu in human pancreatic adenocarcinoma cells

International Nuclear Information System (INIS)

Nayak, Tapan K.; Norenberg, Jeffrey P.; Anderson, Tamara L.; Prossnitz, Eric R.; Stabin, Michael G.; Atcher, Robert W.

2007-01-01

Introduction: Advance clinical cancer therapy studies of patients treated with somatostatin receptor (sstr)-targeted [DOTA 0 -Tyr 3 ]octreotide (DOTATOC) labeled with low-linear-energy-transfer (LET) β - -emitters have shown overall response rates in the range of 15-33%. In order to improve outcomes, we sought to compare the therapeutic effectiveness of sstr-targeted high-LET α-emitting 213 Bi to that of low-LET β - -emitting 177 Lu by determining relative biological effectiveness (RBE) using the external γ-beam of 137 Cs as reference radiation. Methods: Sstr-expressing human pancreatic adenocarcinoma Capan-2 cells and A549 control cells were used for this study. The effects of different radiation doses of 213 Bi and 177 Lu labeled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and sstr-targeted DOTATOC were investigated with a clonogenic cell survival assay. Apoptosis was measured using the Cell Death Detection ELISA PLUS 10x kit. Results: Using equimolar DOTATOC treatment with concurrent irradiation with a 137 Cs source as reference radiation, the calculated RBE of [ 213 Bi]DOTATOC was 3.4, as compared to 1.0 for [ 177 Lu]DOTATOC. As measured in terms of absorbance units, [ 213 Bi]DOTATOC caused a 2.3-fold-greater release of apoptosis-specific mononucleosomes and oligonucleosomes than [ 177 Lu]DOTATOC at the final treatment time of 96 h (P 213 Bi]DOTATOC is therapeutically more effective in decreasing survival than is [ 177 Lu]DOTATOC in human pancreatic adenocarcinoma cells due to its comparatively higher RBE

Recovery of metal chlorides from their complexes by molten salt displacement

International Nuclear Information System (INIS)

McLaughlin, D.F.; Stoltz, R.A.

1989-01-01

This patent describes a process for recovering zirconium or hafnium chloride from a complex of zirconium or hafnium tetrachloride and phosphorus oxychloride. The process comprising: introducing liquid complex of zirconium or hafnium tetrachloride and phosphorus oxychloride into an upper portion of a feed column containing zirconium or hafnium tetrachloride vapor and phosphorus oxychloride vapor. The liquid complex absorbing zirconium or hafnium tetrachloride vapor and producing a bottoms liquid and also producing a phosphorus oxychloride vapor stripped of zirconium or hafnium tetrachloride; introducing the bottoms liquid into a molten salt containing displacement reactor, the reactor containing molten salt comprising at least 30 mole percent lithium chloride and at least 30 mole percent of at least one other alkali metal chloride, the reactor being heated to 30-450 0 C to displace phosphorus oxychloride from the complex and product zirconium or hafnium tetrachloride vapor and phosphorus oxychloride vapor and zirconium or hafnium tetrachloride-containing molten salt; introducing the zirconium or hafnium tetrachloride vapor and the phosphorus oxychloride vapor into the feed column below the point of introduction of the liquid stream; introducing the zirconium or hafnium tetrachloride containing-molten salt into a recovery vessel where zirconium or hafnium tetrachloride is removed from the molten salt to produce zirconium or hafnium tetrachloride product and zirconium or hafnium chloride-depleted molten salt; and recycling the zirconium or hafnium tetachloride-depleted molten salt to the displacement reactor

Synthesis and in vitro evaluation of an antiangiogenic cancer-specific dual-targeting 177Lu-Au-nanoradiopharmaceutical

International Nuclear Information System (INIS)

Gonzalez-Ruiz, Abraham; Ferro-Flores, Guillermina; Azorin-Vega, Erika; Ocampo-Garcia, Blanca; Maria Ramirez, Flor de; Santos-Cuevas, Clara; Luna-Gutierrez, Myrna; Leon-Rodriguez, Luis De; Isaac-Olive, Keila; Morales-Avila, Enrique

2017-01-01

The aim of this research was to synthesize and chemically characterize a cancer-specific 177 Lu-Au-nanoradiopharmaceutical based on gold nanoparticles (NPs), the nuclear localization sequence (NLS)-Arg-Gly-Asp peptide and an aptamer (HS-pentyl-pegaptanib) to target both the α(v)β(3) integrin and the vascular endothelial growth factor (VEGF) overexpressed in the tumor neovasculature, as well as to evaluate by the tube formation assay, the nanosystem capability to inhibit angiogenesis. 177 Lu-NP-RGD-NLS-Aptamer was obtained with a radiochemical purity of 99 ± 1%. Complete inhibition of tube formation (angiogenesis) was demonstrated when endothelial cells (EA.hy926), cultured in a 3D-extracellular matrix support, were treated with the developed nanosystem. (author)

68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology.

Science.gov (United States)

Dalm, Simone U; Bakker, Ingrid L; de Blois, Erik; Doeswijk, Gabriela N; Konijnenberg, Mark W; Orlandi, Francesca; Barbato, Donato; Tedesco, Mattia; Maina, Theodosia; Nock, Berthold A; de Jong, Marion

2017-02-01

Because overexpression of the gastrin-releasing peptide receptor (GRPR) has been reported on various cancer types, for example, prostate cancer and breast cancer, targeting this receptor with radioligands might have a significant impact on staging and treatment of GRPR-expressing tumors. NeoBOMB1 is a novel DOTA-coupled GRPR antagonist with high affinity for GRPR and excellent in vivo stability. The purpose of this preclinical study was to further explore the use of NeoBOMB1 for theranostic application by determining the biodistribution of 68 Ga-NeoBOMB1 and 177 Lu-NeoBOMB1. PC-3 tumor-xenografted BALB/c nu/nu mice were injected with either approximately 13 MBq/250 pmol 68 Ga-NeoBOMB1 or a low (∼1 MBq/200 pmol) versus high (∼1 MBq/10 pmol) peptide amount of 177 Lu-NeoBOMB1, after which biodistribution and imaging studies were performed. At 6 time points (15, 30, 60, 120, 240, and 360 min for 68 Ga-NeoBOMB1 and 1, 4, 24, 48, 96, and 168 h for 177 Lu-NeoBOMB1) postinjection tumor and organ uptake was determined. To assess receptor specificity, additional groups of animals were coinjected with an excess of unlabeled NeoBOMB1. Results of the biodistribution studies were used to determine pharmacokinetics and dosimetry. Furthermore, PET/CT and SPECT/MRI were performed. Injection of approximately 250 pmol 68 Ga-NeoBOMB1 resulted in a tumor and pancreas uptake of 12.4 ± 2.3 and 22.7 ± 3.3 percentage injected dose per gram (%ID/g) of tissue, respectively, at 120 min after injection. 177 Lu-NeoBOMB1 biodistribution studies revealed a higher tumor uptake (17.9 ± 3.3 vs. 11.6 ± 1.3 %ID/g of tissue at 240 min after injection) and a lower pancreatic uptake (19.8 ± 6.9 vs. 105 ± 13 %ID/g of tissue at 240 min after injection) with the higher peptide amount injected, leading to a significant increase in the absorbed dose to the tumor versus the pancreas (200 pmol, 570 vs. 265 mGy/MBq; 10 pmol, 435 vs. 1393 mGy/MBq). Using these data to predict patient dosimetry, we found

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)

Absolute El Transition Probabilities in the Deformed Nuclei {sup 177}Yb and {sup 1}

Energy Technology Data Exchange (ETDEWEB)

Malmskog, Sven G

1964-08-15

The absolute E1-transition probabilities have been measured for two 7/2{sup -} (514) levels populated from the short-lived isomers {sup 177m}Yb (6.4 sec) and {sup 179m}Hf (18.6 sec), a delayed coincidence set up being used for the purpose. This gave a half life of T{sub 1/2} = (4.48 {+-} 0.08)x10{sup -9} sec for the 104 keV level in {sup 177}Yb and T{sub 1/2} = (1.86 {+-} 0.05)x10{sup -9} sec for the 217 keV level in {sup 179}Hf. The result has been compared with the calculations made by Nilsson. The effect of the pairing correlation has also been taken into account. An agreement with the experimental values to within a factor of three is obtained. An extrapolated estimate of the half life for the 408.9 keV 7/2{sup -} (514) level in {sup 181}W gives 3x10{sup -11} sec.

Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

International Nuclear Information System (INIS)

Araujo, Bortoleti de; Pujatti, Priscilla Brunelli; Barrio, Ofelia; Caldeira, Jose S.; Mengatti, Jair; Suzuki, Miriam F.

2008-01-01

Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 ( 177 Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177 Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177 Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

[Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto].

Science.gov (United States)

Sampaio, Inês Lucena; Luiz, Henrique Vara; Violante, Liliana Sobral; Santos, Ana Paula; Antunes, Luís; Torres, Isabel; Sanches, Cristina; Azevedo, Isabel; Duarte, Hugo

2016-11-01

The purpose of this article is to report the experience of the Portuguese Institute of Oncology - Porto in the treatment of gastroenteropancreatic neuroendocrine tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality. A retrospective analysis of clinical reports of patients with gastroenteropancreatic neuroendocrine tumors undergoing treatment with 177Lu-DOTA-TATE between April 2011 and November 2013 was performed. Thirty six cases were reviewed and 30 completed all 3 cycles of 177Lu-DOTA-TATE (83.3%). In these patients it was registered: acute side effects in 8.9% of cycles; grade 3 CTCAE liver toxicity in 13.3% of patients (all with previous abnormal liver function); absence of significant renal or hematologic toxicity; symptomatic improvement in 71.4% of patients; median overall time to progression of 25.6 months; median overall survival from diagnosis of 121.7 months. Patients with higher expression of somatostatin receptors had longer progression-free survival and overall survival times (p DOTA-TATE is an effective, safe and well-tolerated treatment, as evidenced in our study by the following findings: symptomatic improvement in most patients and increased time to disease progression and survival (especially in those with higher sstr expression), with acute and significant subacute/chronic side effects reported only in a minority of cases. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is a promising treatment for patients with gastroenteropancreatic neuroendocrine tumors, with demonstrated benefits in terms of safety and efficacy.

The challenges of treating paraganglioma patients with {sup 177}Lu-DOTATATE PRRT: Catecholamine crises, tumor lysis syndrome and the need for modification of treatment protocols

Energy Technology Data Exchange (ETDEWEB)

Makis, William; Mccann, Karey; Mcewan, Alexander J. B. [Dept. of Diagnostic Imaging, Cross Cancer Institute, Alberta (China)

2015-09-15

A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted radioisotope therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with {sup 177}Lu-[DOTA0,Tyr3]octreotate (DOTATATE) radioisotope therapy using established protocols. Three paraganglioma patients were treated with 4–5 cycles of {sup 177}Lu-DOTATATE and were evaluated for side effects and response to therapy. Two of the three patients developed severe adverse reactions following their first {sup 177}Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2–4 h and by reducing the administered dose of {sup 177}Lu-DOTATATE. Subsequent {sup 177}Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to therapy was achieved in all three patients, resulting in significantly improved quality of life. {sup 177}Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions.

Formulation of an inhibitor radiopharmaceutical of prostatic antigen of 177Lu-Glu-Nh-CO-Nh-Lys membrane

International Nuclear Information System (INIS)

Ortega S, D.

2015-01-01

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 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 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 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 177 LuCl 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)

Synthesis, analysis, purification and biodistribution in an animal model of radiopharmaceutical 177Lu3+ -dotatato for diagnostic and therapeutic use in neuroendocrine tumors

International Nuclear Information System (INIS)

Caldeira Filho, Jose de Souza

2009-01-01

The aim of this work was to propose rationalization in the synthesis, analysis and purification of radiopharmaceutical 177 Lu 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 177 Lu 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 : 26μg) for that from the Oak Ridge National Laboratory /USA, and 1:16 (370 MBq: 11.8 μg) 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 177 Lu 3+ - DOTATATO permits high economy in production costs. Chemical studies on the synthesis of radiopharmaceuticals also placed in evidence the interference of 177 Hf 4+ , the decay product of 177 Lu 3= , as the 177 Lu 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)

Growth of HfO{sub x} thin films by reactive molecular beam epitaxy

Energy Technology Data Exchange (ETDEWEB)

Hildebrandt, Erwin; Kurian, Jose; Alff, Lambert [Institut fuer Materialwissenschaft, TU Darmstadt (Germany)

2008-07-01

Thin films of hafnium oxide were grown on single crystal r-cut and c-cut sapphire by reactive molecular beam epitaxy. The conditions for the growth of single oriented hafnium oxide thin films have been established. Hafnium oxide thin films were characterized by X-ray diffraction and optical absorption measurements. It was found that hafnium oxide thin films grown on r-cut sapphire were (00l) oriented whereas, on c-cut sapphire, hafnium oxide films showed different orientations depending on the growth temperature and oxidation conditions. The hafnium oxide films grown at higher temperature and under strong oxidation conditions yielded (001) oriented films on c-cut sapphire whereas slightly weaker oxidation condition leads to (111) oriented hafnium oxide films. The bandgap deducted from optical absorption measurement carried out on hafnium oxide films grown under optimized conditions agreed well with the values reported in literature. A range of oxygen deficient thin films of hafnium oxide were also grown on single crystal sapphire substrates in order to investigate the effect of oxygen vacancies on dielectric properties of hafnium oxide. The oxygen deficient thin films of hafnium oxide show a decrease in bandgap with increase in oxygen deficiency.

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

Evaluation and Enhancement of the Oxygen Reduction Reaction Activity on Hafnium Oxide Nanoparticles Assisted by L(+)-lysine

International Nuclear Information System (INIS)

Chisaka, Mitsuharu; Itagaki, Noriaki

2016-01-01

Evaluation of the oxygen reduction reaction (ORR) on oxide compounds is difficult owing to the insulating nature of oxides. In this study, various amounts of L(+)-lysine were added to the precursor dispersion for the hydrothermal synthesis of hafnium oxide nanoparticles on reduced graphene oxide sheets (HfO_x–rGO) to coat the HfO_x catalysts with layers of carbon, thereby increasing the conductivity and number of active sites. When the mass ratio of L(+)-lysine to GO, R, was above 26, carbon layers were formed and the amount monotonically increased with increasing R, as noted by cyclic voltammogrametry. X-ray photoelectron spectroscopy and rotating disk electrode analyses revealed that pyrolysis produced ORR-active oxygen defects, whose formation was proposed to involve carbothermal reduction. When 53 ≤ R ≤ 210, HfO_x–rGO contained a similar amount of oxygen defects and ORR activity, as represented by an onset potential of 0.9 V versus the reversible hydrogen electrode in 0.1 mol dm"−"3 H_2SO_4. However, the number of active sites depended on R due to the amount of L(+)-lysine-derived carbon layers that increased both the number of active sites and resistivity towards oxygen diffusion.

Mechanistic Studies of Hafnium-Pyridyl Amido-Catalyzed 1-Octene Polymerization and Chain Transfer Using Quench-Labeling Methods.

Science.gov (United States)

Cueny, Eric S; Johnson, Heather C; Anding, Bernie J; Landis, Clark R

2017-08-30

Chromophore quench-labeling applied to 1-octene polymerization as catalyzed by hafnium-pyridyl amido precursors enables quantification of the amount of active catalyst and observation of the molecular weight distribution (MWD) of Hf-bound polymers via UV-GPC analysis. Comparison of the UV-detected MWD with the MWD of the "bulk" (all polymers, from RI-GPC analysis) provides important mechanistic information. The time evolution of the dual-detection GPC data, concentration of active catalyst, and monomer consumption suggests optimal activation conditions for the Hf pre-catalyst in the presence of the activator [Ph 3 C][B(C 6 F 5 ) 4 ]. The chromophore quench-labeling agents do not react with the chain-transfer agent ZnEt 2 under the reaction conditions. Thus, Hf-bound polymeryls are selectively labeled in the presence of zinc-polymeryls. Quench-labeling studies in the presence of ZnEt 2 reveal that ZnEt 2 does not influence the rate of propagation at the Hf center, and chain transfer of Hf-bound polymers to ZnEt 2 is fast and quasi-irreversible. The quench-label techniques represent a means to study commercial polymerization catalysts that operate with high efficiency at low catalyst concentrations without the need for specialized equipment.

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.

Characteristics of laser produced plasmas of hafnium and tantalum in the 1-7 nm region

Science.gov (United States)

Li, Bowen; Otsuka, Takamitsu; Sokell, Emma; Dunne, Padraig; O'Sullivan, Gerry; Hara, Hiroyuki; Arai, Goki; Tamura, Toshiki; Ono, Yuichi; Dinh, Thanh-Hung; Higashiguchi, Takeshi

2017-11-01

Soft X-ray (SXR) spectra from hafnium and tantalum laser produced plasmas were recorded in the 1-7 nm region using two Nd:YAG lasers with pulse lengths of 170 ps and 10 ns, respectively, operating at a range of power densities. The maximum focused peak power density was 2. 3 × 1014 W cm-2 for 170 ps pulses and 1. 8 × 1012 W cm-2 for 10 ns pulses, respectively. Two intense quasicontinuous intensity bands resulting from n = 4 - n = 4 and n = 4 - n = 5 unresolved transition arrays (UTAs) dominate both sets of experimental spectra. Comparison with calculations performed with the Cowan suite of atomic structure codes as well as consideration of previous experimental and theoretical results aided identification of the most prominent features in the spectra. For the 10 ns spectrum, the highest ion stage that could be identified from the n = 4 - n = 5 arrays were lower than silver-like Hf25+ and Ta26+ (which has a 4 d 104 f ground configuration) indicating that the plasma temperature attained was too low to produce ions with an outermost 4 d subshell, while for the 170 ps plasmas the presence of significantly higher stages was deduced and lines due to 4 d-5 p transitions were clearly evident. Furthermore, we show an enhancement of emission from tantalum using dual laser irradiation, and the effect of pre-pulse durations and delay times between two pulses are demonstrated.

Preparation and biological evaluation of {sup 177}Lu conjugated PR81 for radioimmunotherapy of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Salouti, Mojtaba, E-mail: saloutim@yahoo.com [Department of Biology, Faculty of Sciences, Zanjan Branch, Islamic Azad University, Zanjan 45156-58145 (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Biomolecule Laboratory, Radioisotope Department, Nuclear Science and Technology Research Institute, Tehran 14144-1339 (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of); Rasaee, Mohammad javad [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of)

2011-08-15

Aim: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. Materials and Methods: The radiochemical purity and in vitro stability of {sup 177}Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor. Results: The radiochemical purity was 91.2{+-}3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1{+-}3.4% and 76.2{+-}3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4{+-}2.4%. The cell toxicity study showed that the complex inhibited 85.2{+-}3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity. Conclusion: The results showed that one may consider {sup 177}Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations.

Reducing Renal Uptake of {sup 177}Lu Labeled CCK Derivative using Basic Amino Acids

Energy Technology Data Exchange (ETDEWEB)

Lee, Soyoung; Lim, Jaecheong; Joh, Eunha [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-05-15

Radiolabeled peptides have been designed to target the relative receptors overespressed in tumor cells, such as integrin αvβ3, gastrin-releasing peptide receptor (GRPR), melanocortin-1 receptor (MC1-R), glucagon-like peptide-a receptor (GLP-1R), and cholecystokinin (CCK) receptor. Most of these peptides are eliminated from the body via the kidney and are partly reabsorbed in the proximal tubular cells. However, the high renal uptake of the radiolabeled peptides may lead to renal toxicity. In this study we investigated various amino acid solutions to reduce the renal uptake of {sup 177}Lu-DOTA-CCK derivative. Renal uptake of {sup 177}Lu-DOTA-CCK derivative is effectively reduced by the administration of positively charged amino acids. The administration of 12 mg of L-lysine was as effective in reducing the renal uptake as 6 mg of lysine and 6 mg of arginine combinations. Further studies will be performed to identify the most potent inhibitor of renal reuptake of radiolabeled peptides and minimize the chance of unwanted side effects.

A study on metal organic framework (MOF-177) synthesis, characterization and hydrogen adsorption -desorption cycles

Energy Technology Data Exchange (ETDEWEB)

Viditha, V.; Venkateswer Rao, M.; Srilatha, K.; Himabindu, V. [Centre for Environment, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, A.P. (India); Yerramilli, Anjaneyulu [Director, TLGVRC, JSU Box 18739, JSU, Jackson, MS 32917-0939 (United States)

2013-07-01

Hydrogen has long been considered to be an ideal alternative to fossil-fuel systems and much work has now been done on its storage. There are four main methods of hydrogen storage: as a liquid; as compressed hydrogen; in the form of metal hydrides; and by physisorption. Among all the materials metal organic frameworks (MOFs) are considered to have desirable properties like high porosity, pore volume and high thermal stability. MOF-177 is considered to be an ideal storage material. In this paper we study about its synthesis and hydrogen storage capacities of MOF-177 at different pressures ranging from 25, 50, 75 and 100 bar respectively. The obtained samples are characterized by XRD, BET and SEM. The recorded results show that the obtained hydrogen capacity is 1.1, 2.20, 2.4 and 2.80 wt%. The desorption capacity is 0.9, 2.1, 2.37 and 2.7 wt% at certain temperatures like 373 K.

X-ray tube target

International Nuclear Information System (INIS)

Weber, R.G.

1980-01-01

A target with an improved heat emissive surface for use in a rotating anode type x-ray tube is described. The target consists of a body having a first surface portion made of x-ray emissive material and a second surface portion made of a heat emissive material comprising at least one of hafnium boride, hafnium oxide, hafnium nitride, hafnium silicide, and hafnium aluminide. (U.K.)

Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice.

Science.gov (United States)

Li, Xia; Risbrough, Victoria B; Cates-Gatto, Chelsea; Kaczanowska, Katarzyna; Finn, M G; Roberts, Amanda J; Markou, Athina

2013-07-01

γ-Aminobutyric acid B (GABAB) receptor activation is a potential therapeutic approach for the treatment of drug addiction, pain, anxiety, and depression. However, full agonists of this receptor induce side-effects, such as sedation, muscle relaxation, tolerance, and cognitive disruption. Positive allosteric modulators (PAMs) of the GABAB receptor may have similar therapeutic effects as agonists with superior side-effect profiles. The present study behaviorally characterized N-([1R,2R,4S]-bicyclo[2.2.1]hept-2-yl)-2-methyl-5-(4-[trifluoromethyl]phenyl)-4-pyrimidinamine (BHF177), a GABAB receptor PAM, in mouse models of anxiety-like behavior, learning and memory. In addition, the effects of BHF177 were compared with the agonist baclofen. Unlike the anxiolytic chlordiazepoxide, baclofen (0.5, 1.5, and 2.5 mg/kg, intraperitoneally) and BHF177 (10, 20, and 40 mg/kg, orally) had no effect on anxiety-like behavior in the elevated plus maze, light/dark box, or Vogel conflict test. Baclofen increased punished drinking in the Vogel conflict test, but this effect may be attributable to the analgesic actions of baclofen. At the highest dose tested (2.5 mg/kg), baclofen-treated mice exhibited sedation-like effects (i.e., reduced locomotor activity) across many of the tests, whereas BHF177-treated mice exhibited no sedation-like effects. BHF177 exhibited pro-convulsion properties only in mice, but not in rats, indicating that this effect may be species-specific. At doses that were not sedative or pro-convulsant, baclofen and BHF177 had no selective effects on fear memory retrieval in contextual and cued fear conditioning or spatial learning and memory in the Barnes maze. These data suggest that BHF177 has little sedative activity, no anxiolytic-like profile, and minimal impairment of learning and memory in mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Study of the radiolabeling of substance P with Lutetium-177 and analysis of the stability in vitro: development of new radiopharmaceutical for tumor treatment

International Nuclear Information System (INIS)

Lima, Clarice Maria de; Pujatti, Priscilla Brunelli; Mengatti, Jair Mengatti; Araujo, Elaine Bortoleti de

2009-01-01

Substance P (SP) is an 11- amino acid neuropeptide, which is known as an important member of the family of the tachykinins, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH2. Radiolabeled SP has been described and proposal for detection and treatment of diseases such as arthritis and tumors. SP is the most important target of neurokinin 1 (NK-1) receptors, over expressed in malignant gliomas. 177 Lu is commonly used in the production of radiopharmaceuticals for treatment of neuroendocrine tumors and is a radionuclide with favorable properties for endo radiotherapy. The half-life of 177 Lu is 6.75 days and it emits b- particles of 497 keV average energy. Moreover, 177 Lu also emits g radiation of 208 keV average energy, which makes imaging diagnosis possible. There are few studies describing radiolabeled SP analogs in literature and the objective of this work was to study the radiolabeling conditions and the stability of SP complexed to DOTA chelator, using 177 Lu as radionuclide, in order to determine the best radiolabeling methodology. A high radiochemical purity (> 95%) and high specific activity of DOTA-SP was achieved when the reaction time was 30 minutes, the temperature was 90 deg C, the mass of DOTA-SP was 10 mg and 177 Lu activity was 185 MBq. These conditions extrapolate will be used in future experiments with high activity and also in in vitro and in vivo studies involving glioma models. (author)

Design and optimization of the production process of radiopharmaceutical 177Lu-DOTA-Nal3-Octreotide for the treatment of gastro-entero-pancreatic tumors

International Nuclear Information System (INIS)

Sanchez G, M. F.

2013-01-01

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 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 ( 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 177 Lu-DOTA-Nal 3 -Octreotide ( 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 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 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 Instituto Nacional de

Preparation and preclinical evaluation of (177)Lu-nimotuzumab targeting epidermal growth factor receptor overexpressing tumors

Czech Academy of Sciences Publication Activity Database

Beckford, Denis R.; Eigner, Sebastian; Eigner-Henke, Kateřina; Lebeda, Ondřej; Melichar, František; Beran, Miloš

2012-01-01

Roč. 39, č. 1 (2012), s. 3-13 ISSN 0969-8051 R&D Projects: GA MŠk 2B06165 Institutional research plan: CEZ:AV0Z10480505 Keywords : Radioimmunotherapy * Nimotuzumab * (177)Lu * Monoclonal antibody Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.517, year: 2012

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)

DNA damage in blood lymphocytes in patients after {sup 177}Lu peptide receptor radionuclide therapy

Energy Technology Data Exchange (ETDEWEB)

Eberlein, Uta; Bluemel, Christina; Buck, Andreas Konrad; Werner, Rudolf Alexander; Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nowak, Carina; Scherthan, Harry [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany)

2015-10-15

The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with {sup 177}Lu-labelled DOTATATE/DOTATOC. The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time-activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with {sup 131}I and {sup 177}Lu. The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. Measurements of RIF and the absorbed dose to the blood after systemic administration of {sup 177}Lu may be used to obtain data on the individual dose-response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. (orig.)

Materials properties of hafnium and zirconium silicates: Metal interdiffusion and dopant penetration studies

Science.gov (United States)

Quevedo Lopez, Manuel Angel

Hafnium and Zirconium based gate dielectrics are considered potential candidates to replace SiO2 or SiON as the gate dielectric in CMOS processing. Furthermore, the addition of nitrogen into this pseudo-binary alloy has been shown to improve their thermal stability, electrical properties, and reduce dopant penetration. Because CMOS processing requires high temperature anneals (up to 1050°C), it is important to understand the diffusion properties of any metal associated with the gate dielectric in silicon at these temperatures. In addition, dopant penetration from the doped polysilicon gate into the Si channel at these temperatures must also be studied. Impurity outdiffusion (Hf, Zr) from the dielectric, or dopant (B, As, P) penetration through the dielectric into the channel region would likely result in deleterious effects upon the carrier mobility. In this dissertation extensive thermal stability studies of alternate gate dielectric candidates ZrSixOy and HfSixO y are presented. Dopant penetration studies from doped-polysilicon through HfSixOy and HfSixOyNz are also presented. Rutherford Backscattering Spectroscopy (RBS), Heavy Ion RBS (HI-RBS), X-ray Photoelectron Spectroscopy (XPS), High Resolution Transmission Electron Microscopy (HR-TEM), and Time of Flight and Dynamic Secondary Ion Mass Spectroscopy (ToF-SIMS, D-SIMS) methods were used to characterize these materials. The dopant diffusivity is calculated by modeling of the dopant profiles in the Si substrate. In this disseration is reported that Hf silicate films are more stable than Zr silicate films, from the metal interdiffusion point of view. On the other hand, dopant (B, As, and P) penetration is observed for HfSixO y films. However, the addition of nitrogen to the Hf - Si - O systems improves the dopant penetration properties of the resulting HfSi xOyNz films.

Effects of therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate on endocrine function

Energy Technology Data Exchange (ETDEWEB)

Teunissen, Jaap J.M.; Kwekkeboom, Dik J. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Jong, Frank H. de; Feelders, Richard A.; Aken, Maarten O. van; Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

2009-11-15

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 {+-} 16 to 25 {+-} 4 ng/l, p < 0.05) and follicle-stimulating hormone (FSH) levels increased (5.9 {+-} 0.5 to 22.7 {+-} 1.4 IU/l, p < 0.05). These levels returned to near baseline levels. Total testosterone and sex hormone binding globulin (SHBG) levels decreased (15.0 {+-} 0.9 to 10.6 {+-} 1.0 nmol/l, p < 0.05 and 61.8 {+-} 8.7 to 33.2 {+-} 3.7 nmol, p < 0.05), respectively, whereas non-SHBG-bound T did not change. An increase (5.2 {+-} 0.6 to 7.7 {+-} 0.7 IU/l, p < 0.05) of luteinizing hormone (LH) levels was found at 3 months of follow-up returning to baseline levels thereafter. In 21 postmenopausal women, a decrease in levels of FSH (74.4 {+-} 5.6 to 62.4 {+-} 7.7 IU/l, p < 0.05) and LH (26.8 {+-} 2.1 to 21.1 {+-} 3.0 IU/l, p < 0.05) was found. Of 66 patients, 2 developed persistent primary hypothyroidism. Free thyroxine (FT{sub 4}) levels decreased (17.7 {+-} 0.4 to 15.6 {+-} 0.6 pmol/l, p < 0.05), whereas thyroid-stimulating hormone (TSH) and triiodothyronine (T{sub 3}) levels did not change. Reverse triiodothyronine (rT{sub 3}) levels decreased (0.38 {+-} 0.03 to 0.30 {+-} 0.01 nmol/l, p < 0.05). Before and after therapy adrenocorticotropic hormone (ACTH) stimulation tests showed an adequate response of serum cortisol (> 550 nmol/l, n = 18). Five patients developed elevated HbA{sub 1c} levels (> 6.5%). In men {sup 177}Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non

Evaluation of detectors for blood bioanalysis in Lu-177 and I-131 therapies for bone marrow dosimetry; Avaliacao de detectores para bioanalise de sangue em terapias com Lu-177 and I-131 para dosimetria de medula ossea

Energy Technology Data Exchange (ETDEWEB)

Degenhardt, Amilie Louize

2016-10-01

The measures traceability is mandatory for minimizing uncertainties in internal dosimetry for radiopharmaceuticals clinical studies and ensures the quality of the standard. Equipment should have resolution and efficiency compatible with radionuclides energies and, additionally, be able to quantify variations in human bodies' activities samples since the initial administration near the minimum residual activities. For testing three equipment (ionization chamber Capintec 25R, sodium iodine scintillator LTI Genesys Gamma-1 and high hyperpure germanium detector Canberra), they were prepared Lu-177 and I-131 radiation sources simulating patient's blood samples activities by adopting the following hypothesis: (1) initial activities according the Brazilian protocols; (2) blood volume in the whole body (5.3 L for adult men and 1.4 L for 5 years-old children); (3) effective half-lives (1.61 h and 42.9 h for Lu-177 bi-exponential adjustment and 15.7 h for I-131 mono-exponential adjustment); (4) sampling between 30 min and 168 h; (v) blood density adjustments. The standard sources were measured in the secondary standard ionization chamber Centronics IG11 at the Laboratorio Nacional de Metrologia das Radiacoes Ionizantes. The Capintec ionization chamber efficiencies ranged, respectively for I-131 and Lu-177, between (111.58±0.02)% and (102.27±0.01)% and HPGe semiconductor detector efficiencies ranged, respectively, between (89.40±0.03)% and (87.80±0.04)%. For the NaI detector, when the Lu-177 sources were positioned inside the detector the efficiencies ranged between (12.66±0.01)% and (11.54± 0.07)% and when the sources were positioned at 5 cm and 10 cm from the detector the efficiencies decreased to less than 5%. For I-131 sources positioned inside the detector, the efficiencies ranged between (29.76±0.21)% and (30.20±0.04)% and they decreased to less than 5% when they were positioned at 5 cm and 10 cm from the detector (deviation greater than 95

Labelling of 90Y- and 177Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated, and Fully Automated Synthesis

Directory of Open Access Journals (Sweden)

Michele Iori

2017-01-01

Full Text Available In spite of the hazard due to the radiation exposure, preparation of 90Y- and 177Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177Lu- and 90Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617 was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90Y- and 177Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90Y-DOTATOC were 96.2±4.9%, 90.3±5.6%, and 82.0±8.4%, while for 177Lu-DOTATOC they were 98.3%  ± 0.6, 90.8%  ± 8.3, and 83.1±5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15±0.4 mSv/GBq, 0.04±0.1 mSv/GBq, and 0.11±0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02±0.008 mSv/GBq, 0.01±0.03 mSv/GBq, and 0.01±0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system.

Comparison of sequential planar 177Lu-DOTA-TATE dosimetry scans with 68Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy

International Nuclear Information System (INIS)

Sainz-Esteban, Aurora; Carril, Jose Manuel; Prasad, Vikas; Schuchardt, Christiane; Zachert, Carolin; Baum, Richard P.

2012-01-01

The aim of the study was to compare sequential 177 Lu-DOTA-TATE planar scans ( 177 Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic 68 Ga-DOTA-TATE positron emission tomography (PET)/CT ( 68 Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods. A total of 44 patients (59 ± 11 years old) with biopsy-proven NET underwent 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE imaging within 7.9 ± 7.5 days between the two examinations. 177 Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on 177 Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on 68 Ga-DOTA-TATE studies obtained before PRRT. A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were 68 Ga-DOTA-TATE positive and 177 Lu-DOTA-TATE negative, whereas 9 were 68 Ga-DOTA-TATE negative and 177 Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for 177 Lu-DOTA-TATE as compared to 68 Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) 177 Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p max ). However, concordant liver lesions with a score from 1 to 3 in the 72-h 177 Lu-DOTA-TATE scan had a lower SUV max

Lifetime embrittlement of reactor core materials

International Nuclear Information System (INIS)

Kreyns, P.H..; Bourgeois, W.F.; Charpentier, P.L.; Kammenzind, B.F.; Franklin, D.G.; White, C.J.

1994-08-01

Over a core lifetime, the reactor materials Zircaloy-2, Zircaloy-4, and hafnium may become embrittled due to the absorption of corrosion- generated hydrogen and to neutron irradiation damage. Results are presented on the effects of fast fluence on the fracture toughness of wrought Zircaloy-2, Zircaloy-4, and hafnium; Zircaloy-4 to hafnium butt welds; and hydrogen precharged beta treated and weld metal Zircaloy-4 for fluences up to a maximum of approximately 150 x 10 24 n/M 2 (> 1 Mev). While Zircaloy-4 did not exhibit a decrement in K IC due to irradiation, hafnium and butt welds between hafnium and Zircaloy-4 are susceptible to embrittlement with irradiation. The embrittlement can be attributed to irradiation strengthening, which promotes cleavage fracture in hafnium and hafnium-Zircaloy welds, and, in part, to the lower chemical potential of hydrogen in Zircaloy-4 compared to hafnium, which causes hydrogen, over time, to drift from the hafnium end toward the Zircaloy-4 end and to precipitate at the interface between the weld and base-metal interface. Neutron radiation apparently affects the fracture toughness of Zircaloy-2, Zircaloy-4, and hafnium in different ways. Possible explanations for these differences are suggested. It was found that Zircaloy-4 is preferred over Zircaloy-2 in hafnium-to- Zircaloy butt-weld applications due to its absence of a radiation- induced reduction in K IC plus its lower hydrogen absorption characteristics compared with Zircaloy-2

The energy landscape of glassy dynamics on the amorphous hafnium diboride surface

International Nuclear Information System (INIS)

Nguyen, Duc; Girolami, Gregory S.; Mallek, Justin; Cloud, Andrew N.; Abelson, John R.; Lyding, Joseph; Gruebele, Martin

2014-01-01

Direct visualization of the dynamics of structural glasses and amorphous solids on the sub-nanometer scale provides rich information unavailable from bulk or conventional single molecule techniques. We study the surface of hafnium diboride, a conductive ultrahigh temperature ceramic material that can be grown in amorphous films. Our scanning tunneling movies have a second-to-hour dynamic range and single-point current measurements extend that to the millisecond-to-minute time scale. On the a-HfB 2 glass surface, two-state hopping of 1–2 nm diameter cooperatively rearranging regions or “clusters” occurs from sub-milliseconds to hours. We characterize individual clusters in detail through high-resolution (<0.5 nm) imaging, scanning tunneling spectroscopy and voltage modulation, ruling out individual atoms, diffusing adsorbates, or pinned charges as the origin of the observed two-state hopping. Smaller clusters are more likely to hop, larger ones are more likely to be immobile. HfB 2 has a very high bulk glass transition temperature T g , and we observe no three-state hopping or sequential two-state hopping previously seen on lower T g glass surfaces. The electronic density of states of clusters does not change when they hop up or down, allowing us to calibrate an accurate relative z-axis scale. By directly measuring and histogramming single cluster vertical displacements, we can reconstruct the local free energy landscape of individual clusters, complete with activation barrier height, a reaction coordinate in nanometers, and the shape of the free energy landscape basins between which hopping occurs. The experimental images are consistent with the compact shape of α-relaxors predicted by random first order transition theory, whereas the rapid hopping rate, even taking less confined motion at the surface into account, is consistent with β-relaxations. We make a proposal of how “mixed” features can show up in surface dynamics of glasses

Targeted radionuclide therapy with RAFT-RGD radiolabelled with (90)Y or (177)Lu in a mouse model of αvβ3-expressing tumours.

Science.gov (United States)

Bozon-Petitprin, A; Bacot, S; Gauchez, A S; Ahmadi, M; Bourre, J C; Marti-Batlle, D; Perret, P; Broisat, A; Riou, L M; Claron, M; Boturyn, D; Fagret, D; Ghezzi, Catherine; Vuillez, J P

2015-02-01

The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β(-) emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD and (90)Y-RAFT-RAD or (177)Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of (90)Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of (177)Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of (90)Y-RAFT-RAD or 37 MBq of (177)Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of (90)Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. (90)Y-RAFT-RGD and (177)Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy.

[Comment to DPR 177/011].

Science.gov (United States)

De Santis, Anna Elisa

2012-01-01

The subject of this study is the analysis of DPR 177/2011 regarding occupational safety in confined environments suspected of pollution The study wishes to represent a platform for the knowledge of the relevant principles and issues that are the functional basis for occupational health professionals, to offer a scheme in which it is possible to implement local actions of occupational prevention in the confined spaces and to help Italian intervention plans Italian within the European area, such, e.g., the present "Healthy workplaces campaign working together for risk prevention" promoted by the European Agency for Safety and Health at Work. The interiorization of this behavioural scheme is needed for professionals and authorities in the occupational safety systems, both public and private, who have the institutional duty to obtain trheir effectiveness. To observe the safety system in the specific matter of confined spaces, their essential elements were considered. These elements were identified both in the DPR 177/2011 and in other pertinent documents. This study doesn't pretend to identify all relevant documents, but wishes to underline the open structure of the system for acquiring non strictly juridical documents, such as ICOH guidelines and International code of ethics for occupational health professionals and pertinent authorities. A specific matter of the study is the different role of rules and ethical principles in verifying the adequacy of the safety system. The role of guidelines and ethic principles in the internal evaluation of legal value was examined for their relevance in order to decide on adequacy of the employer's management in safety matter adequacy which can by evaluated looking at his effective knowledge of spaces and good selection of managers and professionals. Furthermore, the study establishes how central--in reaching the safety--is the method based on effectiveness in managing the prevention in occupational health. The managerial method

Prototype vibration measurement program for reactor internals (177-fuel assembly plant). Supplement 1

International Nuclear Information System (INIS)

Simonis, J.C.; Post, R.C.; Thoren, D.E.

1976-08-01

The surveillance specimen holder tubes installed in the Babcock and Wilcox 177-fuel assembly plants have been redesigned. The structural adequacy of this design has been verified through extensive analysis. The design adequacy will be further confirmed by measuring the vibrational response of the surveillance specimen holder tube during normal and transient flow operation. This report describes the vibration measurement program that will be conducted at Toledo Edison's Davis Besse 1 site

Indigenous development of TBq levels of "1"7"7Lu radioisotope production at RPhD for nuclear medicine applications - a successful venture

International Nuclear Information System (INIS)

Chakraborty, Sudipta; Vimalnath, K.V.; Dash, Ashutosh

2017-01-01

Lutetium-177 ("1"7"7Lu) has emerged as a potential radionuclide during last decade for the development of radionuclide therapy owing to its favorable nuclear decay characteristics (T_1_/_2=6.65 d, E_β_(_m_a_x) = 0.497 MeV, E_γ = 113 keV (6.4%) and 208 keV (11%)). The long half-life of this promising radioisotope offering distinct logistical advantage and feasibility of its large-scale production in medium flux Dhruva research reactor contributed to its success story

Evaluation of detectors for blood bioanalysis in Lu-177 and I-131 therapies for bone marrow dosimetry

International Nuclear Information System (INIS)

Degenhardt, Amilie Louize

2016-01-01

The measures traceability is mandatory for minimizing uncertainties in internal dosimetry for radiopharmaceuticals clinical studies and ensures the quality of the standard. Equipment should have resolution and efficiency compatible with radionuclides energies and, additionally, be able to quantify variations in human bodies' activities samples since the initial administration near the minimum residual activities. For testing three equipment (ionization chamber Capintec 25R, sodium iodine scintillator LTI Genesys Gamma-1 and high hyperpure germanium detector Canberra), they were prepared Lu-177 and I-131 radiation sources simulating patient's blood samples activities by adopting the following hypothesis: (1) initial activities according the Brazilian protocols; (2) blood volume in the whole body (5.3 L for adult men and 1.4 L for 5 years-old children); (3) effective half-lives (1.61 h and 42.9 h for Lu-177 bi-exponential adjustment and 15.7 h for I-131 mono-exponential adjustment); (4) sampling between 30 min and 168 h; (v) blood density adjustments. The standard sources were measured in the secondary standard ionization chamber Centronics IG11 at the Laboratorio Nacional de Metrologia das Radiacoes Ionizantes. The Capintec ionization chamber efficiencies ranged, respectively for I-131 and Lu-177, between (111.58±0.02)% and (102.27±0.01)% and HPGe semiconductor detector efficiencies ranged, respectively, between (89.40±0.03)% and (87.80±0.04)%. For the NaI detector, when the Lu-177 sources were positioned inside the detector the efficiencies ranged between (12.66±0.01)% and (11.54± 0.07)% and when the sources were positioned at 5 cm and 10 cm from the detector the efficiencies decreased to less than 5%. For I-131 sources positioned inside the detector, the efficiencies ranged between (29.76±0.21)% and (30.20±0.04)% and they decreased to less than 5% when they were positioned at 5 cm and 10 cm from the detector (deviation greater than 95

76 FR 16379 - Foreign-Trade Zone 177-Evansville, IN; Application for Manufacturing Authority, Best Chair, Inc...

Science.gov (United States)

2011-03-23

...--Evansville, IN; Application for Manufacturing Authority, Best Chair, Inc. d/b/a Best Home Furnishings... Zones Board (the Board) by the Ports of Indiana, grantee of FTZ 177, requesting manufacturing authority on behalf of Best Chair, Inc. d/b/a Best Home Furnishings (Best Home), to manufacture upholstered...

Dosimetry for {sup 177}Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Delker, Andreas; Fendler, Wolfgang Peter; Brunegraf, Anika; Gosewisch, Astrid; Gildehaus, Franz Josef; Bartenstein, Peter; Boening, Guido [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Kratochwil, Clemens; Haberkorn, Uwe [Heidelberg University Hospital, Department for Nuclear Medicine, Heidelberg (Germany); Tritschler, Stefan; Stief, Christian Georg [Ludwig-Maximilians-University of Munich, Department of Urology, Munich (Germany); Kopka, Klaus [German Cancer Research Center (dkfz), Division of Radiopharmaceutical Chemistry, Heidelberg (Germany)

2016-01-15

Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand {sup 177}Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) {sup 177}Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with {sup 177}Lu-DKFZ-PSMA-617. We suggest that {sup 177}Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour

Application of analytic methodologies for image quantification in neuroendocrine tumor therapy with {sup 177}Lu-DOTA

Energy Technology Data Exchange (ETDEWEB)

Kubo, T.T.A.; Oliveira, S.M.V. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Marco, L.; Mamede, M., E-mail: tadeukubo@gmail.com [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil)

2012-07-01

Neuroendocrine tumors have annual incidence of 1 to 2 cases per one hundred thousand inhabitants. The {sup 177}Lu-DOTA-octreotate treatments in 3 or 4 cycles has been effective in controlling disease progression and, in some cases, promote tumor remission. To estimate radiation side effects in healthy organs, image quantification techniques have been broadcast for individualized patient dosimetry. In this paper, image data processing methods are presented to allowing comparisons between different image conjugate views, combined with attenuation correction and system sensitivity. Images were acquired 24, 72 and 192 h after administration of 74 GBq of {sup 177}Lu-DOTA using a dual-head gamma camera detection system and they were evaluated with ImageJ software. 4 female patients underwent to two cycles of treatment. The kidneys, liver and whole-body regions of interest were separately assessed by 4 techniques for counts method and 12 techniques for pixel intensity method, considering the main photopeak separately and aided by the attenuation correction map and adjacent windows to photopeak energy. The pixel intensity method was combined with mathematical correction for pixels with null value. The results obtained by the two methods were strongly correlated (r>0.9) (p<0.001). The paired t-test accepted the null hypothesis of compatibility between the two methods (with and without attenuation correction map) (p<0.05), but rejected it when the adjacent windows were combined. No significant tumor reduction (p>0.05) was found between the treatment cycles. In conclusion, the pixel intensity method is faster and allows macros, minimizing operator error, and may optimize dosimetry in tumor therapies with {sup 177}Lu-DOTA-octreotate. (author)

Indirect and direct measurement of thermal neutron acceleration by inelastic scattering on the 177Lu isomer

International Nuclear Information System (INIS)

Belier, G.; Roig, O.; Meot, V.; Daugas, J.M.; Aupiais, J.; Jutier, Ch.; Le Petit, G.; Veyssiere, Ch.

2008-01-01

When neutrons interact with isomers, these isomers can de-excite and in such a reaction the outgoing neutron has an energy greater than the in-going one. This process is referred as Inelastic Neutron Acceleration or Super-elastic Scattering. Up to now this process was observed for only two nucleus, 152m Eu and 180m Hf by measuring the number of fast neutrons produced by isomeric targets irradiated with thermal neutrons. In these experiments the energies of the accelerated neutrons were not measured. This report presents an indirect measurement of inelastic neutron acceleration on 177m Lu, based on the burn-up and the radiative capture cross sections measurements. Since at thermal energies the inelastic scattering and the radiative capture are the only processes that contribute to the isomer burn-up, the inelastic cross section can be deduced from the difference between the two measured quantities. Applying this method for the 177 Lu isomer with different neutron fluxes we obtained a value of (257 ± 50) barns (for a temperature of 323 K) and determined that there is no integral resonance for this process. In addition the radiative capture cross section on 177g Lu was measured with a much better accuracy than the accepted value. Since the acceleration cross section is quite high, a direct measurement of this process was undertaken, sending thermal neutrons and measuring the fast neutrons. The main goal now is to measure the outgoing neutron energies in order to identify the neutron transitions in the exit channel. In particular the K conservation question can be addressed by such a measurement. (author)

Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers.

Science.gov (United States)

Villard, Linda; Romer, Anna; Marincek, Nicolas; Brunner, Philippe; Koller, Michael T; Schindler, Christian; Ng, Quinn K T; Mäcke, Helmut R; Müller-Brand, Jan; Rochlitz, Christoph; Briel, Matthias; Walter, Martin A

2012-04-01

Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes. In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) or with cycles alternating between [(90)Y-DOTA]-TOC and (177)lutetium-labeled DOTA-TOC ([(177)Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles. A total of 486 patients completed three or more treatment cycles; 237 patients received [(90)Y-DOTA]-TOC and 249 patients received [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC. Patients receiving [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC had a significantly longer survival than patients receiving [(90)Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups. [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC was associated with improved overall survival compared with [(90)Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.

Phase II study of radiopeptide {sup 177}Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours

Energy Technology Data Exchange (ETDEWEB)

Claringbold, Phillip G. [Fremantle Hospital, Department of Oncology, Fremantle, WA (Australia); Brayshaw, Paul A.; Turner, J.H. [University of Western Australia, Department of Nuclear Medicine, Fremantle Hospital, Fremantle, WA (Australia); Price, Richard A. [Fremantle Hospital, Department of Radiology, Fremantle, WA (Australia)

2011-02-15

In this phase II study we investigated the safety and efficacy of combination capecitabine and {sup 177}Lu-octreotate for the treatment of disseminated, progressive, unresectable neuroendocrine tumours (NETs). Enrolled in the study were 33 patients with biopsy-proven NETs, positive {sup 111}In-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq {sup 177}Lu-octreotate 8-weekly, with 14 days of 1,650 mg/m{sup 2} capecitabine per day. Of the 33 patients, 25 completed four cycles. Minimal transient myelosuppression at 3-4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia. Nephrotoxicity was absent. Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy, and showed cumulative doses all below toxic thresholds. Objective response rates (ORR) were 24% partial response (PR), 70% stable disease (SD) and 6% progressive disease. Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months (range 5-33 months). Survival at 1 and 2 years was 91% (95% CI 75-98%) and 88% (95% CI 71-96%), respectively. The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of {sup 177}Lu-octreotate radiopeptide therapy and led to an ORR of 24% PR and 70% minor response or SD in patients with progressive metastatic NETs. Tumour control and stabilization of disease was obtained in 94% of these patients. (orig.)

Correlations between cultured pearl size parameters and PIF-177 biomarker expression in Pinctada margaritifera families reared in two contrasting environments

Science.gov (United States)

Blay, Carole; Parrad, Sophie; Cabral, Philippe; Aiho, Vaite; Ky, Chin-Long

2016-12-01

The black-lipped pearl oyster, Pinctada margaritifera, produces the largest and most valuable coloured pearls in the world. Cultured pearl size remains one of the most important quality traits. Despite the great geographical area covered by pearl farms in the atolls of French Polynesia, little is known about the influence of grow-out site effects on pearl size attained. To explore the genetic and environmental impact on the size of pearls as well as the genetic × environment interaction, a uniform experimental graft was designed on two contrasting macro-geographical lagoons. Five biparental families of donor oysters were grafted and then reared at both sites. After 18 months of culture, phenotypic parameters corresponding to pearl size, i.e. nacre weight and thickness, were recorded among the harvested pearls. The expression of Pif-177 gene, a biomarker encoding protein in the aragonite nacreous layer, was analysed in the corresponding pearl sac. The results show a family effect for nacre weight and thickness on both sites, with family F058 producing the heaviest and thickest nacre, and F805 the lightest and thinnest. By contrast, inter-site comparison revealed no significant site effects for these two parameters. In addition, grow-out location did not modify the relative gene expression of Pif-177 in the pearl sac between donor families in either culture site. Both nacre weight and thickness were positively correlated with the level gene expression of Pif-177. These results suggest that pearl size parameters were not affected by the environment in the present study and this is supported by the relative gene expression of Pif-177 observed. This knowledge constitutes an initial step in the study of pearl size trait inheritance, which will be helpful in the near future for the diffusion of genetically selected donor oyster lines produced by hatchery systems throughout production sites.

An Auger electron spectroscopy study on the anodization process of high-quality thin-film capacitors made of hafnium

International Nuclear Information System (INIS)

Noya, Atsushi; Sasaki, Katsutaka; Umezawa, Toshiji

1989-01-01

Formation process of the anodic oxide film of hafnium for use as a thin-film capacitor has been examined by the current-voltage characteristics of the anodization and the in-depth analysis of formed oxide using Auger electron spectroscopy. It is found that the oxide growth obeys three different rate laws such as the linear rate law at first and next the parabolic rate law during the constant current anodization, and then the reciprocal logarithmic rate law during the constant voltage anodization following after the constant current process. From the Auger electron spectroscopy analysis, it is found that the shape of the compositional depth profile of the grown oxide film varies associating with the rate law of oxidation obeyed. The variation of depth profile correlating with the rate law is discussed with respect to each elementary process such as the transport and/or the reaction of chemical species interpreted from the over-all behavior of anodization process. It is revealed that the stoichiometric film having an interface with sharp transition, which is favorable for obtaining excellent electrical properties of the capacitor, can be obtained under the condition that the phase-boundary reaction is the rate-determining step of the anodization. The constant voltage anodization process also satisfies such circumstances and therefore can be favorable method for preparing highquality thin-film capacitors. (author)

Contribution towards ALD and MOCVD of rare earth oxides and hafnium oxide. From precursor evaluation to process development and thin film characterization

International Nuclear Information System (INIS)

Xu, Ke

2013-01-01

elements for ALD applications. A possible synthesis route is the salt metatheses route. It could be expected that the monodentate guanidine ligand would provide increased reactivity towards water, where the bulky guanidine ligands will shield the RE center providing self-limiting growth behavior. In Chapter 4 and 7, ALD of rare earth oxides and hafnium oxide using corresponding guanidinate precursors are in detail investigated. According to the measurements, these processes are true ALD processes with broad ALD windows, high growth per cycle in the saturated area. Furthermore, the rare earth guanidinate and hafnium guanidinate precursors exhibit matching ALD window in the temperature range of 200 - 225 C. This motivated us to deposite trinary oxide thin films (HfREOx) using corresponding precursor combinations.

The efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Kim, Seong-Jang; Pak, Kyoungjune [Pusan National University Hospital, Department of Nuclear Medicine and Biomedical Research Institute, Busan (Korea, Republic of); Koo, Phillip J.; Kwak, Jennifer J.; Chang, Samuel [University of Colorado School of Medicine, Department of Radiology, Aurora, CO (United States)

2015-12-15

This study was performed to evaluate the efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of ''neuroendocrine'', ''{sup 177}Lu'' and ''prognosis''. All published studies of neuroendocrine tumours treated with {sup 177}Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8 % with a pooled effect of 29 % [95 % confidence interval (CI) 24-34 %]. Disease control rates ranged from 71.8 to 100 %. The random-effects model showed an average disease control rate of 81 % (95 % CI 71-91 %). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5 % with a pooled effect of 23 % (95 % CI 11-38 %). Disease control rates ranged from 73.9 to 89.1 %. The random-effects model showed an average disease control rate of 82 % (95 % CI 71-91 %). {sup 177}Lu-labelled PRRT is an effective treatment

Targeted radionuclide therapy with RAFT-RGD radiolabelled with {sup 90}Y or {sup 177}Lu in a mouse model of αvβ3-expressing tumours

Energy Technology Data Exchange (ETDEWEB)

Bozon-Petitprin, A.; Bacot, S.; Ahmadi, M.; Marti-Batlle, D.; Perret, P.; Broisat, A.; Riou, L.M. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); Gauchez, A.S.; Bourre, J.C.; Fagret, D.; Vuillez, J.P. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); CHRU Grenoble, Hopital Michallon, Service de Medecine Nucleaire, Grenoble (France); Claron, M.; Boturyn, D. [CNRS, UMR 5250, Departement de Chimie Moleculaire, Grenoble (France); Ghezzi, Catherine [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); INSERM U1039, Radiopharmaceutiques biocliniques, Batiment Jean Roget, Domaine de la Merci, Faculte de Medecine, La Tronche (France)

2014-08-28

The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK]){sub 4} (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β{sup -} emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD and {sup 90}Y-RAFT-RAD or {sup 177}Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of {sup 90}Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of {sup 177}Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of {sup 90}Y-RAFT-RAD or 37 MBq of {sup 177}Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of {sup 90}Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. {sup 90}Y-RAFT-RGD and {sup 177}Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy. (orig.)

High clinical and morphologic response using 90Y-DOTA-octreotate sequenced with 177Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.

Science.gov (United States)

Kong, Grace; Callahan, Jason; Hofman, Michael S; Pattison, David A; Akhurst, Tim; Michael, Michael; Eu, Peter; Hicks, Rodney J

2017-03-01

Bulky disease is an adverse prognostic factor for 177 Lu-DOTA-octreotate ( 177 Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). 90 Y-DOTA-octreotate ( 90 Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than 177 Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of 90 Y-DOTATATE followed by 2-3 cycles of 177 Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq 90 Y-DOTATATE, and 21 GBq 177 Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with 90 Y -DOTATATE followed by 177 Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved

Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE: the IEO phase I-II study

Energy Technology Data Exchange (ETDEWEB)

Bodei, Lisa; Grana, Chiara M.; Baio, Silvia M.; Lombardo, Dario; Chinol, Marco; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta; Ferrari, Mahila E. [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Fazio, Nicola [European Institute of Oncology, Division of Medical Oncology, Milan (Italy); Iodice, Simona [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Bartolomei, Mirco [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); M. Bufalini Hospital, Division of Nuclear Medicine, Cesena, FC (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Unit of Radiometabolic Medicine, Meldola, FC (Italy)

2011-12-15

Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst{sub 2}), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of {sup 177}Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst{sub 2}-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of {sup 177}Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. {sup 177}Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. (orig.)

177Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

International Nuclear Information System (INIS)

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

2010-01-01

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 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 μg ml -1 , 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.

Indirect and direct measurement of thermal neutron acceleration by inelastic scattering on the {sup 177}Lu isomer

Energy Technology Data Exchange (ETDEWEB)

Belier, G.; Roig, O.; Meot, V.; Daugas, J.M. [CEA Bruyeres-le-Chatel, Dept. de Physique Theorique et Appliquee, 91 (France); Aupiais, J.; Jutier, Ch.; Le Petit, G. [CEA Bruyeres-le-Chatel, Service de Physique Nucleaire, 91 (France). Dept. de Physique Theorique et Appliquee; Letourneau, A.; Marie, F. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, Service de Physique Nucleaire, 91- Gif sur Yvette (France); Veyssiere, Ch. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, Service d' Ingenierie des Systemes, 91- Gif sur Yvette (France)

2008-07-01

When neutrons interact with isomers, these isomers can de-excite and in such a reaction the outgoing neutron has an energy greater than the in-going one. This process is referred as Inelastic Neutron Acceleration or Super-elastic Scattering. Up to now this process was observed for only two nucleus, {sup 152m}Eu and {sup 180m}Hf by measuring the number of fast neutrons produced by isomeric targets irradiated with thermal neutrons. In these experiments the energies of the accelerated neutrons were not measured. This report presents an indirect measurement of inelastic neutron acceleration on {sup 177m}Lu, based on the burn-up and the radiative capture cross sections measurements. Since at thermal energies the inelastic scattering and the radiative capture are the only processes that contribute to the isomer burn-up, the inelastic cross section can be deduced from the difference between the two measured quantities. Applying this method for the {sup 177}Lu isomer with different neutron fluxes we obtained a value of (257 {+-} 50) barns (for a temperature of 323 K) and determined that there is no integral resonance for this process. In addition the radiative capture cross section on {sup 177g}Lu was measured with a much better accuracy than the accepted value. Since the acceleration cross section is quite high, a direct measurement of this process was undertaken, sending thermal neutrons and measuring the fast neutrons. The main goal now is to measure the outgoing neutron energies in order to identify the neutron transitions in the exit channel. In particular the K conservation question can be addressed by such a measurement. (author)

Comparison of sequential planar {sup 177}Lu-DOTA-TATE dosimetry scans with {sup 68}Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy

Energy Technology Data Exchange (ETDEWEB)

Sainz-Esteban, Aurora; Carril, Jose Manuel [Hospital Universitario Marques de Valdecilla, Department of Nuclear Medicine, Santander (Spain); Prasad, Vikas; Schuchardt, Christiane; Zachert, Carolin; Baum, Richard P. [Zentralklinik Bad Berka, Department of Nuclear Medicine and Centre for PET/CT, Bad Berka (Germany)

2012-03-15

The aim of the study was to compare sequential {sup 177}Lu-DOTA-TATE planar scans ({sup 177}Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic {sup 68}Ga-DOTA-TATE positron emission tomography (PET)/CT ({sup 68}Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods. A total of 44 patients (59 {+-} 11 years old) with biopsy-proven NET underwent {sup 68}Ga-DOTA-TATE and {sup 177}Lu-DOTA-TATE imaging within 7.9 {+-} 7.5 days between the two examinations. {sup 177}Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on {sup 177}Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on {sup 68}Ga-DOTA-TATE studies obtained before PRRT. A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were {sup 68}Ga-DOTA-TATE positive and {sup 177}Lu-DOTA-TATE negative, whereas 9 were {sup 68}Ga-DOTA-TATE negative and {sup 177}Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for {sup 177}Lu-DOTA-TATE as compared to {sup 68}Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) {sup 177}Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p < 0.05). No such significance was

Nano-crystals of cerium–hafnium binary oxide: Their size-dependent structure

Energy Technology Data Exchange (ETDEWEB)

Raitano, Joan M. [Department of Applied Physics and Applied Mathematics, Materials Science and Engineering Program, Columbia University, New York, NY 10027 (United States); Khalid, Syed [National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY 11973 (United States); Marinkovic, Nebojsa [Chemical Engineering Department, Columbia University, 500 W 120th St, Mudd 801, New York, NY 10027 (United States); Chan, Siu-Wai, E-mail: sc174@columbia.edu [Department of Applied Physics and Applied Mathematics, Materials Science and Engineering Program, Columbia University, New York, NY 10027 (United States)

2015-09-25

Highlights: • (1 − x)CeO{sub 2}–xHfO{sub 2} was precipitated (0 < x < 1) and calcined in air. • For x ⩽ 0.14, crystallites ⩽140 nm in size exhibit only the fluorite structure. • This low hafnia solubility is attributable to no auto-reduction (Ce{sup 3+} = 0). • The low solubility is also due to the high temperature required for homogenization. • Coarsening is lessened as Hf{sup 4+} ions slow cation diffusion in these crystallites. - Abstract: Cerium oxide (CeO{sub 2}, “ceria”) and hafnium oxide (HfO{sub 2}, “hafnia”) were aqueously co-precipitated and subsequently calcined to allow for homogenization. The size of the (1−x)CeO{sub 2}–xHfO{sub 2} crystallites, determined by the Scherrer equation, varied from 140 nm for x = 0 to 15 nm for x = 0.73. For x ⩽ 0.14, only cubic structures are visible in X-ray diffractograms, and the lattice parameters are consistent with the values expected for structurally cubic solid solutions of hafnia in ceria. At x = 0.26, tetragonal and monoclinic phases nucleated with the former not being observed in the bulk phase diagram for ceria–hafnia. Therefore, the solubility limit of the cubic structure is between x = 0.14 and x = 0.26 for 40–61 nm crystallites, the sizes of these respective compositions. More specifically, for the 40 nm crystallites of x = 0.26 (1 − x)CeO{sub 2}–xHfO{sub 2}, 15% of the hafnia remains in a structurally cubic solid solution with ceria based on the observed cubic lattice parameter. The compositional domain for the cubic fluorite structure in this study is narrower than other nanostructured (1 − x)CeO{sub 2}–xHfO{sub 2} studies, especially studies with crystallite sizes less than 10 nm, but wider than observed in the bulk and helps to expand the size regime over which the relationship between crystallite size and phase stability is known. The extent of this cubic-structure domain is mainly attributable to the intermediate crystallite size and the roughly zero Ce{sup 3

Study of the viability of the production of lutetium - 177 in the nuclear reactor IEA-R1 at IPEN/CNEN-SP; Estudo da viabilidade de producao do lutecio - 177 no reator nuclear IEA-R1 do IPEN/CNEN-SP

Energy Technology Data Exchange (ETDEWEB)

Silva, Giovana Pasqualini da

2008-07-01

The {sup -} emitter {sup 177} Lu is a promising therapeutic radioisotope for the curative treatment of cancer using labelled proteins. It has a half - life of 6.71 day and maximum and average (3 energies of 421 and 133 keV, respectively, resulting in a short range of irradiation of tissue. The decay is accompanied by the emission of low energy -radiation of 208.3 keV (11%) and 113 keV (6.4%), suitable for simultaneous imaging. Lu can be produced by two different routes, namely, by irradiation of natural Lu{sub 2}O{sub 3} target ({sup 176}Lu, 2.6%) or enriched (in {sup 176}Lu) Lu{sub 2}O{sub 3} target, and also by irradiation of Yb target (Yb{sub 2}O{sub 3}) followed by radiochemical separation of Lu from Yb isotopes. The objective of this work is the development of a method of the production of {sup 177} Lu through of the (n, gamma) nuclear reaction, by the direct and indirect method of production. Targets of lutetium oxide and ytterbium oxide were irradiated for evaluation of the activity produced and the chemical separation of lutetium and ytterbium was studied using different ion exchange resins. For the direct method, the best results were obtained using the target Lu{sub 2}O{sub 3} enriched in 39.6%. The best results for the indirect method were achieved with the process of separation using 0.25M - HlBA as eluent. The results showed that it is possible to produce {sup 177} Lu of low specific activity for labeling molecules used for bone pain relief and in radiosynoviortesy. (author)

Numeric modeling of HfO2 neutron flux sensor parameters during sensor burnup in the RBMK-1500 reactor

International Nuclear Information System (INIS)

Jurkevicius, A.; Remeikis, V.

2001-01-01

The isotopic composition of hafnium in the radial neutron flux sensor of the RBMK-1500 reactor, the rates of the neutron absorption on Hf isotopes and the neutron spectrum in the sensor were numerically modeled. The sequence SAS2 (Shielding Analysis Sequence) from the package SCALE 4.3 was used for calculations. It has been obtained that the main neutron absorber 167 Er isotope practically burns up completely at the 18 MW d/kgU burnup depth, and at that time the capture rate of thermal neutrons in erbium decreases ten-fold. The average neutron flux density was calculated 7.6*10 13 neutrons. Cm -2 S -1 in the RBMK-1500 reactor grating, when the nuclear fuel enriched with 235 U by 2.4% and with Er by 0.4% is used in a fuel assembly. When the sensor burnup reaches 28 MW d/kgU, the neutron absorption rate of 178 Hf exceeds the rate of 177 Hf. The overall neutron absorption rate in hafnium decreases 2.53 times due to the sensor burnup to 56 MW d/kgU. The corrective factors ξ d (I) at different integral flux I of the sensors were calculated. The obtained dependence ξ d (I) calculated numerically was compared to the experimental one determined by processing repeated calibration results of Hf sensors in RBMK-1500 reactors, as well as compared to the theoretical one currently used in the Ignalina NPP special mathematical algorithms. (author)

Preparation of (177Lu-DOTAn-PAMAM-[Nimotuzumab-F(ab’2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment

Directory of Open Access Journals (Sweden)

Titis Sekar Humani

2017-12-01

Full Text Available Intact monoclonal antibodies with a high molecular weight tend to have a poor pharmacokinetic profile and tumor penetration, and potential for eliciting host antibody responses. F(ab’2 fragments smaller than intact monoclonal antibodies that still maintain antigen binding could solve this problem. The objective of this study was to optimize the digestion process of nimotuzumab, an anti-EGFR monoclonal antibody, into its F(ab’2 fragment and investigate its potential as a therapeutic radioimmunoconjugate. Optimal conditions for digestion of nimotuzumab to its F(ab’2 fragment were found to be 6 hours of digestion time with a pH of 3.5 and 1:100 mol ratio of pepsin to nimotuzumab. The purity of the F(ab’2-nimotuzumab was confirmed by SDS-PAGE and HPLC analysis. Prior to its labeling with lutetium-177 radionuclide, the nimotuzumab-F(ab’2 was conjugated to DOTA-PAMAM dendrimer [DOTA denotes 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, PAMAM denotes poly(amidoamine] to form conjugate of (DOTAn-PAMAM-[nimotuzumab-F(ab’2]. Radiolabeling of DOTA-PAMAM-[nimotuzumab-F(ab’2] conjugate with 177Lu resulted in (177Lu-DOTAn-PAMAM-[nimotuzumab-F(ab’2] with radiochemical purity > 99% after purification with a PD-10 column. Further studies still need to be performed in order to confirm the potential of this radioimmunoconjugate as a radioimmunotherapeutic agent for EGFR overexpressed cancers.

Preclinical Evaluation of (177)Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor-Overexpressing Tumors

Czech Academy of Sciences Publication Activity Database

Beckford, Denis R.; Eigner, Sebastian; Beran, Miloš; Eigner-Henke, Kateřina; Lázníček, M.; Melichar, František; Chinol, M.

2011-01-01

Roč. 26, č. 3 (2011), s. 287-297 ISSN 1084-9785 R&D Projects: GA MŠk OE08018 Institutional research plan: CEZ:AV0Z10480505 Keywords : EGFR * (177)Lu * monoclonal antibodies * Nimotuzumab Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.787, year: 2011

In vivo quantification of {sup 177}Lu with planar whole-body and SPECT/CT gamma camera imaging

Energy Technology Data Exchange (ETDEWEB)

Bailey, Dale L. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Faculty of Health Sciences, University of Sydney, Cumberland, NSW (Australia); Sydney Medical School, University of Sydney, Camperdown, NSW (Australia); NETwork, Sydney Vital, St Leonards, Sydney, NSW (Australia); Hennessy, Thomas M.; Willowson, Kathy P.; Henry, E. Courtney [Institute of Medical Physics, University of Sydney, Camperdown, NSW (Australia); Chan, David L.H. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); NETwork, Sydney Vital, St Leonards, Sydney, NSW (Australia); Aslani, Alireza [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Roach, Paul J. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Sydney Medical School, University of Sydney, Camperdown, NSW (Australia)

2015-09-17

Advances in gamma camera technology and the emergence of a number of new theranostic radiopharmaceutical pairings have re-awakened interest in in vivo quantification with single-photon-emitting radionuclides. We have implemented and validated methodology to provide quantitative imaging of {sup 177}Lu for 2D whole-body planar studies and for 3D tomographic imaging with single-photon emission computed tomography (SPECT)/CT. Whole-body planar scans were performed on subjects to whom a known amount of [{sup 177}Lu]-DOTA-octreotate had been administered for therapy. The total radioactivity estimated from the images was compared with the known amount of the radionuclide therapy administered. In separate studies, venous blood samples were withdrawn from subjects after administration of [{sup 177}Lu]-DOTA-octreotate while a SPECT acquisition was in progress and the concentration of the radionuclide in the venous blood sample compared with that estimated from large blood pool structures in the SPECT reconstruction. The total radioactivity contained within an internal SPECT calibration standard was also assessed. In the whole-body planar scans (n = 28), the estimated total body radioactivity was accurate to within +4.6 ± 5.9 % (range −17.1 to +11.2 %) of the correct value. In the SPECT reconstructions (n = 12), the radioactivity concentration in the cardiac blood pool was accurate to within −4.0 ± 7.8 % (range −16.1 to +7.5 %) of the true value and the internal standard measurements (n = 89) were within 2.0 ± 8.5 % (range −16.3 to +24.2 %) of the known amount of radioactivity contained. In our hands, state-of-the-art hybrid SPECT/CT gamma cameras were able to provide accurate estimates of in vivo radioactivity to better than, on average, ±10 % for use in biodistribution and radionuclide dosimetry calculations.

L2₁ and XA Ordering Competition in Hafnium-Based Full-Heusler Alloys Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb).

Science.gov (United States)

Wang, Xiaotian; Cheng, Zhenxiang; Wang, Wenhong

2017-10-20

For theoretical designing of full-Heusler based spintroinc materials, people have long believed in the so-called Site Preference Rule (SPR). Very recently, according to the SPR, there are several studies on XA-type Hafnium-based Heusler alloys X₂YZ, i.e., Hf₂VAl, Hf₂CoZ (Z = Ga, In) and Hf₂CrZ (Z = Al, Ga, In). In this work, a series of Hf₂-based Heusler alloys, Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb), were selected as targets to study the site preferences of their atoms by first-principle calculations. It has been found that all of them are likely to exhibit the L2₁-type structure instead of the XA one. Furthermore, we reveal that the high values of spin-polarization of XA-type Hf₂VZ (Z = Al, Ga, In, Tl, Si, Ge, Sn, Pb) alloys have dropped dramatically when they form the L2₁-type structure. Also, we prove that the electronic, magnetic, and physics nature of these alloys are quite different, depending on the L2₁-type or XA-type structures.

Preparation of therapeutic dose of 177Lu-DOTA-TATE using a novel single vial freeze-dried kit: a comparison with 'in-situ' preparation at hospital radiopharmacy.

Science.gov (United States)

Das, Tapas; Banerjee, Sharmila; Shinto, Ajit; Kamaleshwaran, K K; Sarma, H D

2014-01-01

Patient dose of (177)Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either 'in-situ' or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of (177)Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent. Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of (177)Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers. The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of (177)Lu- DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites. The kit was useful for the convenient preparation of therapeutic dose of (177)Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.

27 CFR 25.177 - Evasion of or failure to pay tax; failure to file a tax return.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Evasion of or failure to... Pay Tax § 25.177 Evasion of or failure to pay tax; failure to file a tax return. Sections 5671, 5673, 5684, 6651, and 6656 of Title 26 United States Code provide penalties for evasion or failure to pay tax...

Growth of conductive HfO{sub 2-x} thin films by reactive molecular beam epitaxy

Energy Technology Data Exchange (ETDEWEB)

Hildebrandt, Erwin; Kurian, Jose; Alff, Lambert [Institut fuer Materialwissenschaft, TU Darmstadt (Germany); Kleebe, Hans-Joachim [Institut fuer Angewandte Geowissenschaften, TU Darmstadt (Germany)

2009-07-01

Thin films of oxygen deficient hafnium oxide were grown on single crystal c-cut and r-cut sapphire substrates by reactive molecular beam epitaxy. The oxidation conditions during growth were varied within a wide range using RF-activated oxygen. Hafnium oxide thin films were characterized using X-ray diffraction, resistivity measurements ({rho}-T) and transmission electron microscopy (TEM). The results show a dramatic increase in conductivity of the deposited oxygen deficient hafnium oxide thin films with decreasing oxidation conditions during growth. The electrical properties of deficient hafnium oxide thin films varied from insulating over semiconducting to conducting. X-ray diffraction data as well as TEM data rule out the possibility of conductivity due to metallic hafnium.

Fast voxel-level dosimetry for 177Lu labelled peptide treatments

International Nuclear Information System (INIS)

Hippeläinen, E; Tenhunen, M; Sohlberg, A

2015-01-01

In peptide receptor radionuclide therapy (PRRT), voxel-level radiation absorbed dose calculations can be performed using several different methods. Each method has it strengths and weaknesses; however, Monte Carlo (MC) simulation is presently considered the most accurate method at providing absorbed dose distributions. Unfortunately MC simulation is time-consuming and often impractical to carry out in a clinical practice. In this work, a fast semi-Monte Carlo (sMC) absorbed dose calculation method for 177 Lu PRRT dosimetry is presented. The sMC method is based on a local electron absorption assumption and fast photon MC simulations. The sMC method is compared against full MC simulation code built on PENELOPE (vxlPen) using digital phantoms to assess the accuracy of these assumptions.Due to the local electron absorption assumption of sMC, the potential errors in cross-fire dose from electrons and photons emitted by 177 Lu were first evaluated using an ellipsoidal kidney model by comparing vxlPen and sMC. The photon cross-fire dose from background to kidney and kidney to background with varying kidney-to-background activity concentration ratios were calculated. In addition, kidney to kidney photon and electron cross-dose with different kidney to kidney distances were studied. Second, extended cardiac-torso (XCAT) phantoms were created with liver lesions and with realistic activity distributions and tissue densities. The XCAT phantoms were used to simulate SPECT projections and 3D activity distribution images were reconstructed using an OSEM algorithm. Image-based dose rate distributions were calculated using vxlPen and sMC. Total doses and dose rate volume histograms (DrVH) produced by the two methods were compared.The photon cross-fire dose from the kidney increased the background’s absorbed dose by 5% or more up to 5.8 cm distance with 20 : 1 kidney to background activity concentration ratio. On the other hand, the photon cross-fire dose from the background to

High clinical and morphologic response using {sup 90}Y-DOTA-octreotate sequenced with {sup 177}Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours

Energy Technology Data Exchange (ETDEWEB)

Kong, Grace; Callahan, Jason; Pattison, David A.; Akhurst, Tim; Eu, Peter [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); Hofman, Michael S. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Parkville (Australia); Michael, Michael [Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia)

2017-03-15

Bulky disease is an adverse prognostic factor for {sup 177}Lu-DOTA-octreotate ({sup 177}Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). {sup 90}Y-DOTA-octreotate ({sup 90}Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than {sup 177}Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of {sup 90}Y-DOTATATE followed by 2-3 cycles of {sup 177}Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq {sup 90}Y-DOTATATE, and 21 GBq {sup 177}Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with {sup 90}Y -DOTATATE followed by {sup 177}Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either

Radiolabeled Antibody Fragment for Preparation of (177Lu-DOTAm-PAMAM G3.0-F(ab’2 trastuzumab as a Radiopharmaceutical for Cancer Therapy

Directory of Open Access Journals (Sweden)

R.D. Haryuni

2017-06-01

Full Text Available Several radiolabeled monoclonal antibodies (mAbs have been used as radioimmunotherapy (RIT agents for cancer therapy. The use of mAbs as RIT agents is due to their ability to carry effectors, in the form of radionuclides which emit alpha (α particles, beta (β particles, or auger electrons, and bind specifically to cancer expressed receptor. This paper reports the preparation of radiolabelled trastuzumab in form of (177Lu-DOTAm-PAMAM G3-F(ab'2-trastuzumab, which will be expected as a potential RIT agent for therapy of breast cancer overexpressed human epidermal growth factor receptor 2 (HER2. Due to its reduced molecular weight, the use of F(ab'2-trastuzumab on the aforementioned RIT agent candidate is expected to reach its target much faster compared to the intact trastuzumab. Meanwhile, the role of PAMAM G3 is to increase the specific activity of the radiotherapeutic agent of Lu-177 due to the ability of its 32 –NH2 functional groups that are able to bind many DOTAs (£ 31 which in turn can bind a large number of 177Lu. The preparation was initiated by fragmentation of trastuzumab using pepsin enzyme in 0.02 M acetic acid buffer with a pH of 4.5 to produce F(ab'2-trastuzumab with a purity of 95 % after purification with PD-10 column. The F(ab'2-trastuzumab was then reacted with succinimidyl 4-(N-maleimidomethyl cyclohexane-1-carboxylate (SMCC to produce SMCC-F(ab'2-trastuzumab. The next reaction was to conjugate SMCC-F(ab'2-trastuzumab with DOTA-PAMAM G3.0-SH, which was prepared by reaction NHS-DOTA with PAMAM G3.0 and followed by reacting it with 2-iminothiolane to give (DOTAm-PAMAM G3.0-F(ab'2-trastuzumab. Finally, the (DOTAm-PAMAM G3.0-F(ab'2-trastuzumab was radiolabelled with 177Lu to produce (177Lu-DOTAm-PAMAM G3.0-F(ab'2-trastuzumab, resulting in a radiochemical purity of 98 % after purification with PD-10 column.Received: 31 October 2015; Revised: 30 June 2016; Accepted: 25 September 2016

Safety of multiple repeated cycles of {sup 177}Lu-octreotate in patients with recurrent neuroendocrine tumour

Energy Technology Data Exchange (ETDEWEB)

Yordanova, Anna; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin; Brossart, Peter [University Hospital Bonn, Department of Internal Medicine 3, Bonn (Germany); Gonzalez-Carmona, Maria A.; Strassburg, Christian P. [University Hospital Bonn, Department of Internal Medicine 1, Bonn (Germany)

2017-07-15

Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of {sup 177}Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET. We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles. We observed no life-threatening adverse events (CTC-4) during {sup 177}Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001). Therapy with eight or more cycles of {sup 177}Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET. (orig.)

Hafnium in peralkaline and peraluminous boro-aluminosilicate glass, and glass subcomponents: a solubility study

International Nuclear Information System (INIS)

Davis, Linda L.; Darab, John G.; Qian, Maoxu; Zhao, Donggao; Palenik, Christopher S.; Li, Hong; Strachan, Denis M.; Li, Liyu

2003-01-01

A relationship between the solubility of hafnia (HfO2) and the host glass composition was explored by determining the solubility limits of HfO2 in peralkaline and peraluminous borosilicate glasses in the system SiO2-Al2O3-B2O3-Na2O, and in glasses in the system SiO2-Na2O-Al2O3 in air at 1450 C. The only Hf-bearing phase to crystallize in the peralkaline borosilicate melts is hafnia, while in the boron-free melts sodium-hafnium silicates crystallize. All peraluminous borosilicate melts crystallize hafnia, but the slightly peraluminous glasses also have sector-zoned hafnia crystals that contain Al and Si. The more peraluminous borosilicate glasses also crystallize a B-containing mullite. The general morphology of the hafnia crystals changes as peralkalinity (Na2O/(Na2O+Al2O3)) decreases, as expected in melts with increasing viscosity. In all of the glasses with Na2O > Al2O3, the solubility of hafnia is linearly and positively correlated with Na2O/(Na2O + Al2O3) or Na2O - Al2O3 (excess sodium), despite the presence of 5 to 16 mol% B2O3. The solubility of hafnia is higher in the sodium-aluminum borosilicate glasses than in the sodium-aluminosilicate glasses, suggesting that the boron is enhancing the effect that excess sodium has on the incorporation of Hf into the glass structure. The results of this solubility study are compared to other studies of high-valence cation solubility in B-free silicate melts. From this, for peralkaline B-bearing glasses, it is shown that, although the solubility limits are higher, the solution behavior of hafnia is the same as in B-free silicate melts previously studied. By comparison, also, it is shown that in peraluminous melts, there must be a different solution mechanism for hafnia: different than for peralkaline sodium-aluminum borosilicate glasses and different than for B-free silicate melts studied by others

Hypocalcaemia after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

Energy Technology Data Exchange (ETDEWEB)

Vliet, Esther I. van; Kam, Boen L.R.; Teunissen, Jaap J.M.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus MC, University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Zillikens, M.C.; Peeters, Robin P. [Erasmus MC, University Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus MC, University Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

2013-12-15

The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D{sub 3}, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 {+-} 0.01 to 2.26 {+-} 0.02 mmol/l, p = 0.02). Eight patients (17 %) showed a marked decrease in serum calcium levels with a nadir of {<=}2.10 mmol/l. In five patients (11 %), calcium substitution therapy was prescribed. PTH increased significantly (5.9 {+-} 0.6 to 6.7 {+-} 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 {+-} 3 to 77 {+-} 3 {mu}mol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 {+-} 0.01 at baseline to a nadir of 2.24 {+-} 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22 %) showed a serum calcium nadir of {<=}2.10 mmol/l, and 11

Formulation and characterization of lutetium-177-labeled stannous (tin) colloid for radiosynovectomy.

Science.gov (United States)

Arora, Geetanjali; Singh, Manoranjan; Jha, Pragati; Tripathy, Sarthak; Bal, Chandrasekhar; Mukherjee, Anirban; Shamim, Shamim A

2017-07-01

Easy large-scale production, easy availability, cost-effectiveness, long half-life, and favorable radiation characteristics have made lutetium-177 (Lu) a preferred radionuclide for use in therapy. Lutetium-177-labeled stannous (Lu-Sn) colloid particles were formulated for application in radiosynovectomy, followed by in-vitro and in-vivo characterization. Stannous chloride (SnCl2) solution and Lu were heated together, the pH was adjusted, and the particles were recovered by centrifugation. The heating time and amount of SnCl2 were varied to optimize the labeling protocol. The labeling efficiency (LE) and radiochemical purity (RCP) of the product were determined. The size and shape of the particles were determined by means of electron microscopy. In-vitro stability was tested in PBS and synovial fluid, and in-vivo stability was tested in humans. LE and RCP were greater than 95% and ∼99% (Rf=0-0.1), respectively. Aggregated colloidal particles were spherical (mean size: 241±47 nm). The product was stable in vitro for up to 7 days in PBS as well as in synovial fluid. Injection of the product into the infected knee joint of a patient resulted in its homogenous distribution in the intra-articular space, as seen on the scan. No leakage of activity was seen outside the knee joint even 7 days after injection, indicating good tracer binding and in-vivo stability. Lu-Sn colloid was successfully prepared with a high LE (>95%) and high RCP (99%) under optimized reaction conditions. Because of the numerous benefits of Lu and the ease of preparation of tin colloid particles, Lu-Sn colloid particles are significantly superior to its currently available counterparts for use in radiosynovectomy.