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Sample records for no-carrier added 177lu

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

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    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.

  2. 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.

  3. No-carrier-added [1.sup.11 c]putrescine

    Science.gov (United States)

    McPherson, Daniel W.; Fowler, Joanna S.; Wolf, Alfred P.

    1989-01-01

    The invention relates to a new radiolabeled imaging agent, no-carrier-added [1-.sup.11 C]putrescine, and to the use of this very pure material as a radiotracer with positron emission tomography for imaging brain tumors. The invention further relates to the synthesis of no-carrier-added [1-.sup.11 C]putrescine based on the Michael addition of potassium .sup.11 C-labeled cyanide to acrylonitrile followed by reduction of the .sup.11 C-labeled dinitrile. The new method is rapid and efficient and provides radiotracer with a specific activity greater than 1.4 curies per millimol and in a purity greater than 95%.

  4. Preparation and Preliminary Evaluation of 177Lu-EDTMP

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  5. Species dependent studies of no-carrier-added {sup 93m}Mo: A green method

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    Mandal, Swadesh, E-mail: swadeshchem@rediffmail.co [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Nayak, Dalia [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India)

    2010-10-15

    The present paper reports a combination of radioanalytical and green methodology for the ultra-trace scale speciation of molybdenum. The differential attitude of iron-doped calcium alginate (Fe-CA) and chitosan biopolymers towards no-carrier-added {sup 93m}Mo radionuclide was studied to develop environmentally sustainable speciation methodology in ultra-trace scale. The affinity of {sup 93m}Mo towards the Fe-CA beads is greater than that of chitosan. Species information was obtained by comparing the adsorption profile of {sup 93m}Mo on Fe-CA and chitosan biopolymer with the software code CHEAQS PRO program. From the experimental results it is concluded that no-carrier-added {sup 93m}Mo radionuclide form mononuclear species instead of polynuclear species in aqueous solution. Use of biodegradable, non-toxic biopolymer makes this method a step forward towards green chemistry.

  6. Preparation and Biodistribution Evaluation in Mice of ~(177)Lu-DOTA-TOC

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The study of 177Lu labeled radiopharmaceuticals for cancer therapy is fast emerging as an important part of nuclear medicine. 177Lu-labelling of DOTA derivatized peptide DOTA-TOC (Tyr3-Octreotide) was carried out and biodistribution of 177Lu-DOTA-TOC in normal

  7. Biokinetic study of free {sup 177}Lu in NIH mice

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    Villarreal Jimenez, V.; Crudo, J., E-mail: josierys@yahoo.com [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Rojo, A.M.; Deluca, G.M. [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina)

    2008-07-01

    Full text: {sup 177}Lu has been identified, by the scientific community, as a radionuclide with interesting advantages compared with {sup 90}Y and other beta emitters used in nuclear medicine. This paper analyses the free {sup 177}Lu biokinetic behavior in NIH male mice from activity measurements performed by the Radiopharmacy Division of CNEA (Comision Nacional de Energia Atomica) in the frame of an IAEA (International Atomic Energy Agency) Coordinated Research Project. The study of experimental data is a previous condition that allows drawing the activity-time curves for organs and to know the biodistribution of {sup 177}Lu. The cumulated activity in organs of interest in NIH male mice are calculated and critical organs are identified. The organs selected for analysis in this paper are the liver, kidneys, spleen, stomach, intestine, lungs, skeleton and red marrow. The last one is estimated from the activity measured in blood based on a recognized method published by Sgouros (2000). The results has been extrapolated to human assuming the same biokinetic behaviour as mice being the applicability of the different extrapolation methods also discussed. The direct extrapolation from mice data was the method of election from a radiological protection point of view. The measurement procedures, the data processing, the extrapolation techniques and the analysis performed in this study will contribute as a basis for future research of this group in the area of antibodies and other radiopharmaceutical labeled with {sup 177}Lu. The cumulated activity calculated in each organ is relevant because it makes possible to perform the dose assessment through the application of appropriate dose coefficients. It is a necessary step in order to evaluate the toxicity risk that is required in a pre-clinical study. (author)

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

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    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

  9. Report on short-term side effects of treatments with {sup 177}Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours

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    Essen, Martijn van; Kam, Boen L.; Kwekkeboom, Dik J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Aken, Maarten O. van [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2008-04-15

    Treatment with the radiolabelled somatostatin analogue {sup 177}Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to {sup 177}Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination. Seven patients were treated with 7.4 GBq {sup 177}Lu-octreotate and capecitabine (1650 mg/m{sup 2} per day) for 2 weeks with an intended number of four cycles. Toxicity, and especially haematological and renal parameters, were monitored on a weekly basis for the first two cycles and 4 and 6 weeks after subsequent cycles. None of the patients had hand-foot syndrome. One patient had grade 1 stomatitis occurring after one of four cycles. Grade 3 or 4 leukopenia or neutropenia did not occur. One patient had grade 3 anaemia, but none had grade 4 anaemia. One patient had grade 2 thrombocytopenia after the fourth cycle, and one had grade 3 thrombocytopenia. Grade 4 thrombocytopenia did not occur. No significant changes in serum creatinine levels were observed. None of the patients had symptoms of cardiac ischaemia. Treatment with the combination of {sup 177}Lu-octreotate and capecitabine was feasible and safe considering acute and subacute side effects. We therefore started a randomised, controlled clinical trial to compare this combination with {sup 177}Lu-octreotate as single agent with regard to anti-tumour effects and side effects. (orig.)

  10. Realistic multi-cellular dosimetry for (177)Lu-labelled antibodies: model and application.

    Science.gov (United States)

    Marcatili, S; Pichard, A; Courteau, A; Ladjohounlou, R; Navarro-Teulon, I; Repetto-Llamazares, A; Heyerdahl, H; Dahle, J; Pouget, J P; Bardiès, M

    2016-10-07

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin(®), a novel (177)Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of (177)Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  11. Realistic multi-cellular dosimetry for 177Lu-labelled antibodies: model and application

    Science.gov (United States)

    Marcatili, S.; Pichard, A.; Courteau, A.; Ladjohounlou, R.; Navarro-Teulon, I.; Repetto-Llamazares, A.; Heyerdahl, H.; Dahle, J.; Pouget, J. P.; Bardiès, M.

    2016-10-01

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin®, a novel 177Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of 177Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  12. 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

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    Zambrano R, O. D.

    2015-07-01

    ). To this spectrum was added some of the most relevant Auger and internal conversion electron emissions. On the other hand, an experimental array was used to simulate the presence or absence of fibrosis in a tumor of malignant cells (HeLa cells). With this model the retention of the radiopharmaceuticals {sup 177}Lu-Tyr{sup 3}-octreotate-gold nanoparticles (multimeric system) and {sup 177}Lu-Tyr{sup 3}-octreotate (monomeric system) in the micro environments (without fibrosis and with fibrosis) was determined. The experimental tumoral fibrosis array consists of a multilayer repetitive patter of HeLa cells, collagen and gelatin until completing a culture (in a trans well insert) layer by layer (Lbl) of five coatings of HeLa cells. The Lbl cultures were exposed during 24 h, approximate duplicating time of HeLa cells, separately to: {sup 177}LuCl{sub 3}, {sup 177}Lu-Tyr{sup 3}-octreotate, and {sup 177}Lu-Tyr{sup 3}-octreotate-gold nanoparticles with an initial activity of 26 MBq (700 μCi). The radiopharmaceutical retention was calculated by measuring the retained activity in the trans well inserts (radiopharmaceutical retained by HeLa cells and microenvironment) and in the lower chamber where the radiopharmaceutical permeated. The experimental models were essential to determine the radiopharmaceutical permeability which allowed the calculation of the retained activity fraction, and hence the cumulated activity in regions of interest for each of the different cases. This is needed at the same time for the radiation absorbed dose calculation. In this work it was concluded that the presence or absence of fibrosis and yet more, the multimeric and multivalent nature of the radiopharmaceutical had an effect on the radiation absorbed dose in the cell nucleus and in the tumor microenvironment. (Author)

  13. Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra-arterially for Liver Metastases.

    Science.gov (United States)

    Limouris, G S; Poulantzas, V; Trompoukis, N; Karfis, I; Chondrogiannis, S; Triantafyllou, N; Gennimata, V; Moulopoulou, L-E; Patsouris, E; Nikou, G; Michalaki, V; Fragulidis, G; Paphiti, M; McCready, R V; Colletti, P M; Cook, G J; Rubello, D

    2016-03-01

    In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of In-[DTPA]-octreotide and more recently with non-carrier added (nca) Lu-[DOTA,Tyr]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (In-[DTPA]-octreotide, 22 ± 3.6 nM and nca Lu-[DOTA,Tyr]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. Thirty patients with gastroenteropancreatic (GEP) somatostatin-positive NETs with liver metastases confirmed on biopsy and In-pentetreotide scan were included. They were treated with In-[DTPA]-octreotide (n = 17) or nca Lu-[DOTA,Tyr]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/ 1.0 software. ncaLu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than In-[DTPA]-octreotide (P DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver). Using Lu-[DOTA,Tyr]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with In-[DTPA] octreotide. Residence time of nca Lu-[DOTA,Tyr]-octreotate results in a significantly higher absorbed dose to bone marrow compared with In-[DTPA]-octreotide. However, a drawback of In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with Lu-[DOTA,Tyr]-octreotate.

  14. Production of no carrier added 80mBr for investigation of Auger electron toxicity.

    Science.gov (United States)

    Mease, R C; DeJesus, O T; Gatley, S J; Harper, P V; Desombre, E R; Friedman, A M

    1991-01-01

    80mBr (half-life = 4.43 h) is an Auger electron emitting nuclide with convenient properties for investigating Auger electron cytotoxicity and with potential for labeling in vivo radiotherapeutic agents. We have investigated three cyclotron target systems capable of generating 80mBr of sufficiently high specific radioactivity (no carrier added) for biomedical experiments. A 83Kr gas target irradiated with 21.5 MeV deuterons made 80mBr at a production yield of 1.6 +/- 0.2 mCi/muAh at saturation. A five-fold increase in 80mBr yield was obtained from 15 MeV proton irradiation of thin elemental Se enriched in 80Se targets although technical improvements are expected to further raise this production yield. This route is therefore superior for current medical cyclotrons. Irradiation of a reusable 80Se copper selenide target also yielded multi-millicurie amounts of 80mBr, and recovery of radiobromine by dry distillation is faster and more convenient than in the elemental Se target, but an optimum copper selenide target for 80mBr production has not yet been built.

  15. No-carrier-added synthesis of a 4-methyl-substituted meta-iodobenzylguanidine analogue

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    Vaidyanathan, G. [Department of Radiology, Duke University Medical Center, Box 3808 Radiology, Bryan Research Building, Durham, NC 27710 (United States)]. E-mail: ganesan.v@duke.edu; Affleck, D.J. [Department of Radiology, Duke University Medical Center, Box 3808 Radiology, Bryan Research Building, Durham, NC 27710 (United States); Zalutsky, M.R. [Department of Radiology, Duke University Medical Center, Box 3808 Radiology, Bryan Research Building, Durham, NC 27710 (United States)

    2005-03-01

    Radioiodinated meta-iodobenzylguanidine (MIBG) is used in the diagnosis and therapy of various neuroendocrine tumors. As a part of our efforts to develop an MIBG analogue with improved characteristics for these applications, a synthesis of 3-[{sup 131}I]iodo-4-methylbenzylguanidine ([{sup 131}I]MeIBG) was developed. Unlabeled MeIBG and the tin precursor, N, N'-(bis-tert-butyloxycarbonyl)-N-(4-methyl-3-trimethylstannylbenzyl) guanidine were synthesized in two steps from 3-iodo-4-methylbenzylalcohol. Radioiodinated MeIBG was synthesized at a no-carrier-added level by the iododestannylation of the tin precursor in about 85% radiochemical yield. The accumulation of [{sup 131}I]MeIBG (38.9{+-}3.0% of input counts) by human neuroblastoma SK-N-SH cells in vitro was 87% that of [{sup 125}I]MIBG (44.5{+-}3.0%) and a number of Uptake-1 inhibiting conditions reduced the uptake of both tracers in this cell line to a similar degree suggesting that introduction of a methyl substituent at the 4-position of MIBG did not adversely affect its biological characteristics.

  16. Production, separation and speciation of no-carrier-added Hg radionuclides using greener methodologies

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    Mandal, S.; Nayak, D. [Chemical Sciences Div., Saba Inst. of Nuclear Physics, Kolkata (India)

    2010-07-01

    Species dependent studies of no-carrier-added (nca) mercury were carried out using radioanalytical technique coupled with two greener analytical methodologies. The adsorption of nca {sup 195mg}Hg and {sup 197m}Hg radionuclides on chitosan biopolymer and cloud point extraction (CPE) was studied to develop environmentally sustainable speciation methodologies at ultra trace level. Species information was obtained by comparing the adsorption profile of nca radiomercury on chitosan biopolymer with the software code CHEAQS PRO. Results obtained from the adsorption study were validated by CPE technique using non ionic surfactant and mixed micelle. Both the experiments established that nca Hg existed as Hg(II). The experimental results support the presence of HgCl{sub 2} species over the pH range 2-4, whereas Hg(OH){sub 2} is the main species over the pH range 6-8. Chitosan biopolymer and mixed micelle [Triton-X-114 and cetyltrimethylammonium bromide (CTAB)] constitute an efficient reagent for the preconcentration of ultra trace level mercury. (orig.)

  17. New separation method of no-carrier-added {sup 47}Sc from titanium targets

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    Bartos, B.; Majkowska, A.; Kasperek, A.; Krajewski, S.; Bilewicz, A. [Institute of Nuclear Chemistry and Technology, Warszawa (Poland). Nuclear Chemistry and Radiochemistry Center

    2012-07-01

    Radionuclides with medium energy beta emission and a several day half-life are attractive candidates for radioimmunotherapy. Among the most promising in this category is {sup 47}Sc produced by fast neutron irradiation (E{sub n} > 1 MeV) of titanium target with high energy neutrons in {sup 47}Ti(n,p){sup 47}Sc nuclear reaction. In the previously reported production scheme the dissolution of the TiO{sub 2} target in hot concentrated H{sub 2}SO{sub 4} and evaporation of the resulting solution were the most time-consuming steps. The present paper describes new, simple and efficient production method of {sup 47}Sc, where the slow dissolution of the target is avoided. After irradiation in fast neutron flux {sup 47}TiO{sub 2} and Li{sub 2}{sup 47}TiF{sub 6} targets were dissolved in HF solutions. Next {sup 47}Sc was separated from the target using anion exchange resin Dowex 1 with 0.4 M HF + 0.06 M HNO{sub 3} solution as eluent. The eluted {sup 47}Sc was adsorbed on cation exchange resin and eluted with 0.5 M of ammonium acetate. The 47Sc separation yield in the proposed procedure is about 90% with the separation time less than 2 h. The obtained no-carrier-added {sup 47}Sc was used to label DOTATATE conjugate with 96% labeling yield. (orig.)

  18. 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

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    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

  19. 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.

  20. [{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.

  1. 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

  2. Production of {sup 177}Lu at the new research reactor FRM-II: Irradiation yield of {sup 176}Lu(n,{gamma}){sup 177}Lu

    Energy Technology Data Exchange (ETDEWEB)

    Dvorakova, Z. [Institut fuer Radiochemie der Technischen Universitaet Muenchen, D-85748 Garching (Germany)], E-mail: nov@rad.chemie.tu-muenchen.de; Henkelmann, R.; Lin, X.; Tuerler, A. [Institut fuer Radiochemie der Technischen Universitaet Muenchen, D-85748 Garching (Germany); Gerstenberg, H. [ZWE FRM-II der Technischen, Universitaet Muenchen, D-85748 Garching (Germany)

    2008-02-15

    Due to its physical and chemical characteristics, {sup 177}Lu is a very attractive radionuclide for use in nuclear medicine. This paper introduces a method for a precise calculation of the irradiation yield of {sup 177}Lu produced by neutron activation of {sup 176}Lu in a nuclear reactor. The calculation is based on the Westcott convention which requires the knowledge of the neutron flux parameters. In this work, the neutron flux parameters of the new research reactor FRM-II (Garching, Germany) were determined and the stability of thermal neutron flux and thermal neutron flux temperature was monitored. The comparison of theoretically calculated and experimentally determined yield for {sup 176}Lu(n,{gamma}){sup 177}Lu reaction is presented.

  3. A potencial theranostic agent for EGF-R expression tumors: (177)Lu-DOTA-nimotuzumab.

    Science.gov (United States)

    Calzada, Victoria; Zhang, Xiuli; Fernandez, Marcelo; Diaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Deutscher, Susan L; Balter, Henia; Quinn, Thomas P; Cabral, Pablo

    2012-10-01

    In this work Nimotuzumab (monoclonal antibody, recognizes the EGF-R) was radiolabeled with (177)Lu as a potential cancer therapy radiopharmaceutical. In-vitro cell binding studies and in-vivo biodistribution and imaging studies were performed to determine the radiochemical stability, targeting specificity and pharmacokinetics of the (177)Lu-labeled antibody. Nimotuzumab was derivatized with DOTA-NHS at room temperature for 2 hours. DOTA-Nimotuzumab was radiolabeled with (177)LuCl3 (15 MBq/mg) at 37°C for 1 h. The radiochemical purity was assessed by ITLC, silica gel and by RP-HPLC. Binding specificity studies were performed with EGF-R positive A431 human epithelial carcinoma and EGF-R negative MDA-MB-435 breast carcinoma cells. Biodistribution studies were performed in healthy female CD-1 mice at 1 h, 4 h, 24 h, and A431 xenografted nude mice at 10 min, 1 h, 4 h, 24 h, 48 h, and 96 h. SPECT-CT imaging studies were performed in A431 xenografted mice at 24 h post injection. DOTA-Nimotuzumab was efficiently labeled with (177) LuCl(3) at 37°C. The in vitro stability of labeled product was optimal over 24 h in buffered saline and mouse serum. Specific recognition of EGF-R by (177)Lu-DOTA-Nimotuzumab was observed in A431 cell binding studies. Biodistribution studies demonstrated increasing tumor uptake of (177)Lu-DOTA-Nimotuzumab over time, with tumor to muscle ratios of 6.26, 10.68, and 18.82 at 4 h, 24 h, and 96 h post injection. Imaging of A431 xenografted mice showed high uptake in the tumor. (177)Lu-DOTA-Nimotuzumab has the potential to be a promising therapy agent, which may be useful in the treatment of patients with EGF-R positive cancer.

  4. Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer.

    Science.gov (United States)

    Shi, Jiyun; Liu, Zhaofei; Jia, Bing; Yu, Zilin; Zhao, Huiyun; Wang, Fan

    2010-06-01

    In this study, we reported the preparation and evaluation of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2 (RGD2 = E[c(RGDfK)](2)) as a potential therapeutic radiotracers for the treatment of integrin alpha(v)beta(3)-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100 degrees C and higher DOTA-conjugate concentration were needed for successful (177)Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of (177)Lu-labeled cyclic RGDfK peptides, and (177)Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin alpha(v)beta(3)-positive tumors.

  5. 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.

  6. Standardization and measurement of gamma-ray probability per decay of 177Lu.

    Science.gov (United States)

    Dias, Mauro S; Silva, Fabrício F V; Koskinas, Marina F

    2010-01-01

    The procedure followed by the Nuclear Metrology Laboratory (LMN), at the Nuclear and Energy Research Institute (IPEN), for the primary standardization of (177)Lu is described. This radionuclide is widely used in radiopharmacy due to its convenient half-life and emitted beta ray energies. The (177)Lu solution was supplied during an international comparison sponsored by BIPM in 2009 and the primary standardization has been accomplished by the 4pibeta-gamma coincidence method using a proportional counter in 4pi geometry coupled with two NaI(Tl) scintillation counters. The beta efficiency was varied by placing Collodion and aluminum absorbers over and under the radioactive source. The (177)Lu calibrated sources were also measured in a previously calibrated HPGe spectrometer, in order to obtain the emission probability per decay for the selected gamma-ray transitions. The experimental extrapolation curves were also compared with Monte Carlo simulations by means of code ESQUEMA developed at the LMN.

  7. [177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma.

    Science.gov (United States)

    Sundberg, Asa Liljegren; Gedda, Lars; Orlova, Anna; Bruskin, Alexander; Blomquist, Erik; Carlsson, Jörgen; Tolmachev, Vladimir

    2004-04-01

    Patients with glioblastoma multiforme have a poor prognosis due to recurrences originating from spread cells. The use of radionuclide targeting might increase the chance of inactivating single tumor cells with minimal damage to surrounding healthy tissue. As a target, overexpressed epidermal growth factor receptors (EGFR) may be used. A natural ligand to EGFR, the epidermal growth factor (EGF) is an attractive targeting agent due to its low molecular weight (6 kDa) and high affinity for EGFR. 177Lu (T(1/2) = 6.7 days) is a radionuclide well suited for treatment of small tumor cell clusters, since it emits relatively low-energy beta particles. The goal of this study was to prepare and preclinically evaluate both in vitro and in vivo the [177Lu]Bz-DTPA-EGF conjugate. The conjugate was characterized in vitro for its cell-binding properties, and in vivo for its pharmacokinetics and ability to target EGFR. [177Lu]Bz-DTPA-EGF bound to cultured U343 glioblastoma cells with an affinity of 1.9 nM. Interaction with EGFR led to rapid internalization, and more than 70% of the cell-associated radioactivity was internalized after 30 minutes of incubation. The retention of radioactivity was good, with more than 65% of the 177Lu still cell-associated after 2 days. Biodistribution studies of i.v. injected [177Lu]Bz-DTPA-EGF in NMRI mice demonstrated a rapid blood clearance. Most of the radioactivity was found in the liver and kidneys. The liver uptake was receptor-mediated, since it could be significantly reduced by preinjection of unlabeled EGF. In conclusion, [177Lu]Bz-DTPA-EGF seems to be a promising candidate for locoregional treatment of glioblastoma due to its high binding affinity, low molecular weight, and ability to target EGFR in vivo.

  8. Evaluation of two intraoperative gamma detectors for assessment of (177)Lu activity concentration in vivo.

    Science.gov (United States)

    Sandblom, Viktor; Ståhl, Ingun; Olofsson Bagge, Roger; Forssell-Aronsson, Eva

    2017-12-01

    Patients with somatostatin receptor-expressing neuroendocrine tumours can be treated with intravenously administered (177)Lu-octreotate. Few patients are cured with the present protocol due to the current dose limitation of normal organs at risk, such as the kidneys. By locally administering (177)Lu-octreotate to the liver for the purpose of treating liver metastases, a substantially reduced absorbed dose to organs at risk could be achieved. The development of such a technique requires the capability of measuring the (177)Lu activity concentration in tissues in vivo. The aim of this study was to evaluate different performance parameters of two commercially available intraoperative gamma detectors in order to investigate whether intraoperative gamma detector measurements could be used to determine (177)Lu activity concentration in vivo. Measurements were made using different sources containing (177)Lu. Response linearity, sensitivity, spatial resolution and its depth dependence, organ thickness dependence of the measured count rate and tumour detectability were assessed for two intraoperative gamma detectors. The two detectors (a scintillation and a semiconductor detector) showed differences in technical performance. For example, the sensitivity was higher for the scintillation detector, while the spatial resolution was better for the semiconductor detector. Regarding organ thickness dependence and tumour detectability, similar results were obtained for both detectors, and even relatively small simulated tumours of low tumour-to-background activity concentration ratios could be detected. Acceptable results were obtained for both detectors, although the semiconductor detector proved more advantageous for our purpose. The measurements demonstrated factors that must be corrected for, such as organ thickness or dead-time effects. Altogether, intraoperative gamma detector measurements could be used to determine (177)Lu activity concentration in vivo.

  9. Esthesioneuroblastoma (olfactory neuroblastoma) treated with 111In-octreotide and 177Lu-DOTATATE PRRT.

    Science.gov (United States)

    Makis, William; McCann, Karey; McEwan, Alexander J B

    2015-04-01

    A 51-year-old man with a recurrent metastatic esthesioneuroblastoma (olfactory neuroblastoma) was referred for peptide receptor radionuclide therapy (PRRT). He received 4 treatments of 111In-octreotide over 8 months and 3 treatments of 177Lu-DOTATATE over 4 months, which helped alleviate his symptoms and improved his quality of life; however, the tumor ultimately progressed and he passed away shortly thereafter. PRRT with 111In-octreotide or 177Lu-DOTATATE could play a role in the management of esthesioneuroblastoma.

  10. Predicting the yield of {sup 177}Lu radionuclide produced by the cyclic irradiation technique

    Energy Technology Data Exchange (ETDEWEB)

    Odame Duodu, Godfred, E-mail: jogd14@yahoo.co [Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana); Akaho, Edward H.K.; Serfor-Armah, Yaw [Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana); Nyarko, Benjamin J.B. [National Nuclear Research Institute, Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana); Afi Achoribo, Elom [Radiological and Medical Sciences Research Institute, Ghana Atomic Energy Commission, P.O. Box LG80, Legon Accra (Ghana)

    2011-03-15

    The feasibility study on the production of {sup 177}Lu radioisotope using a low power research reactor has been conducted. A reliable method for predicting the yield of {sup 177}Lu produced using the cyclic activation technique based on the Westcott formalism has been established. A specific activity of 243.24 mCi/g was obtained when a {sup 176}Lu{sub 2}O{sub 3} of natural abundance was irradiated for 4 h and decayed for 20 h for four cycles at GHARR-1 with a neutron flux of 5.0x10{sup 11} ncm{sup -2} s{sup -1}.

  11. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice.

    NARCIS (Netherlands)

    Schoffelen, R.; Graaf, W.T.A. van der; Franssen, G.M.; Sharkey, R.M.; Goldenberg, D.M.; McBride, W.J.; Rossi, E.A.; Eek, A.; Oyen, W.J.G.; Boerman, O.C.

    2010-01-01

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies in combination with a radiolabeled peptide reduces the radiation dose to normal tissues, especially the bone marrow. In this study, the optimization, therapeutic efficacy, and toxicity of PRIT of colon cancer with a (177)Lu-labeled pep

  12. Production of no-carrier-added radiobromine. new nickel selenide target and optimized separation by dry distillation

    Energy Technology Data Exchange (ETDEWEB)

    Breunig, Katharina; Spahn, Ingo; Spellerberg, Stefan; Coenen, Heinz H. [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Neurowissenschaften und Medizin (INM), Nuklearchemie (INM-5)

    2015-07-01

    Nickel(II) selenide (NiSe) was investigated as a new high-current target material for cyclotron production of radiobromine, as it contains a higher amount of selenium and has a lower melting point than the widely used Cu{sub 2}Se. Using a slanted target system, NiSe was successfully tested up to beam currents of 16 μA so far. With regard to the isolation of no-carrier-added (n.c.a.) radiobromide from the target material, an improved dry distillation device with high yields of 76%-86% was developed. The implementation of a special custom-made quartz funnel decreased the dead volume of the apparatus and a quartz capillary for trapping the radiobromine allowed to concentrate the radioactivity in a small volume of less than 100 μL of 0.1 M NaOH, ready for immediate subsequent radiosyntheses. Thus, the new apparatus improves the handling of the isolation procedure and the radioactive product. The radiochemical purity of the resulting solution of n.c.a. [*Br]bromide was verified by radio-IC where no other species were detected.

  13. Separation and purification of no-carrier-added arsenic from bulk amounts of germanium for use in radiopharmaceutical labelling

    Energy Technology Data Exchange (ETDEWEB)

    Jahn, M.; Radchenko, V.; Roesch, F.; Jennewein, M. [Mainz Univ. (Germany). Inst. of Nuclear Chemsistry; Filosofov, D. [Joint Inst. for Nuclear Research, Dubna (Russian Federation). Lab. of Nuclear Problems; Hauser, H.; Eisenhut, M. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Radiopharmaceutical Chemistry

    2010-07-01

    Radioarsenic labelled radiopharmaceuticals could add special features to molecular imaging with positron emission tomography (PET). For example the long physical half-lives of {sup 72}As (T{sub 1/2}=26 h) and {sup 74}As (T{sub 1/2}=17.8 d) in conjunction with their high positron branching rates of 88% and 29%, respectively, allow the investigation of slow physiological or metabolical processes, like the enrichment and biodistribution of monoclonal antibodies in tumour tissue or the characterization of stem cell trafficking. A method for separation and purification of no-carrier-added (nca) arsenic from irradiated metallic germanium targets based on distillation and anion exchange is developed. It finally converts the arsenic into an {sup *}As(III) synthon in PBS buffer and pH 7 suitable for labelling of proteins via As-S bond formations. The method delivers radioarsenic in high purity with separation factors of 10{sup 6} from germanium and an overall yield from target to labelling synthon of > 40%. In a proof-of-principle experiment, the monoclonal antibody Bevacizumab, directed against the human VEGF receptor, was labelled with a radiochemical yield > 90% within 1 h at room temperature with nca {sup 72/74/77}As. (orig.)

  14. Radioiodinated MIBG in paraganglioma and pheochromocytoma: previous results and early experiences using no-carrier-added MIBG

    Energy Technology Data Exchange (ETDEWEB)

    James, Olga [Duke University Medical Center, Box 3949, Durham, NC 27710 (United States)], E-mail: olga.g.james@duke.edu; Coleman, R. Edward [Duke University Medical Center, Box 3949, Durham, NC 27710 (United States)], E-mail: colem010@mc.duke.edu

    2008-08-15

    The majority of pheochromocytomas and paragangliomas are benign, with malignancy occurring in approximately 10% of pheochromocytoma patients. The malignancy rate among paragangliomas is 15-35% or higher if associated with succinate dehydrogenase B gene mutations. The 5-year mortality rate in malignant pheochromocytoma and paraganglioma is nearly 50%. Malignancy of both pheochromocytoma and paraganglioma is determined by the existence of metastasis or local invasion and not by the cellular characteristics. There are no known clinical, biochemical or histopathological differences between pheochromocytoma and paraganglioma. Metaiodobenzylguanidine (MIBG) radiolabeled with either {sup 123}I or {sup 131}I has been used to diagnose neuroendocrine tumors such as paraganglioma and pheochromocytoma, and {sup 131}I-MIBG has been used to treat these tumors. The role of radioiodinated MIBG in treating neuroendocrine tumors is still being evaluated. More recently, no-carrier-added (nca) MIBG has become available, and the advantages of nca MIBG over ca MIBG are being demonstrated. This article reviews the biology of paragangliomas and pheochromocytomas, the role of MIBG imaging in the diagnosis of these tumors and the role of both ca and nca {sup 131}I-MIBG in the treatment of these tumors. New data on nca {sup 131}I-MIBG in the therapy of these tumors are included.

  15. Preparation and Characterization of {sup 177}Lu Labeled Antibody against Tyrosine Kinase Receptor Her2

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Young; Hong, Young-Don; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-05-15

    The tyrosine kinase receptor Her2, also known in humans as erbB2, is a member of the epidermal growth factor receptor (EGFR or erbB1) family. The Her2 is highly expressed in many cancer types and over expressed in approximately 30% of all primary breast cancer. Overexpression of Her2 is associated with a poor prognosis. Her2 is a suitable target because it involves an extracellular domain that can be targeted by antibodies produced by B cells. Based on these advantages, we tried to prepare the {sup 177}Lu labeled Her2 antibody. This radioimmunoconjugate could act by not only blocking the Her2 signalling pathway using antibody but also killing the tumour cell using {beta} energy of {sup 177}Lu.

  16. Quantitative (177)Lu SPECT imaging using advanced correction algorithms in non-reference geometry.

    Science.gov (United States)

    D'Arienzo, M; Cozzella, M L; Fazio, A; De Felice, P; Iaccarino, G; D'Andrea, M; Ungania, S; Cazzato, M; Schmidt, K; Kimiaei, S; Strigari, L

    2016-12-01

    Peptide receptor therapy with (177)Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of (177)Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher (177)Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using μ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of (177)Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators.

  17. {sup 177}Lu-DOTA-lanreotide: a novel tracer as a targeted agent for tumor therapy

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Sharmila; Das, Tapas; Chakraborty, Sudipta; Samuel, Grace; Korde, Aruna; Srivastava, Sudha; Venkatesh, Meera E-mail: meerav@apsara.barc.ernet.in; Pillai, M.R.A

    2004-08-01

    {sup 177}Lu of specific activity {approx}100-110 TBq/g and radionuclidic purity of {approx}100% was obtained by irradiation of enriched Lu{sub 2}O{sub 3} (60.6% {sup 176}Lu) target for 7 days at a thermal neutron flux of 3x10{sup 13}n/cm{sup 2}/sec. The {sup 177}Lu labeling of a macrocyclic bifunctional chelating agent viz. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) has been extensively studied. Lanreotide, [{beta}-naphthyl-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH{sub 2}] a disulfide-linked cyclic octapeptide and a somatostatin analog, reported to bind with a wide variety of tumors expressing somatostatin receptors, was conjugated with DOTA. The peptide-BFCA conjugate was characterized with the help of high-resolution two-dimensional proton NMR spectroscopy. The {sup 177}Lu labeling of the DOTA-lanreotide conjugate has been standardized to give a radiolabeling yield of 85%. The tracer showed specific binding with A-431 human epidermoid carcinoma and IMR-32 human brain neuroblastoma cells.

  18. 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.)

  19. Gamma camera calibration and validation for quantitative SPECT imaging with (177)Lu.

    Science.gov (United States)

    D'Arienzo, M; Cazzato, M; Cozzella, M L; Cox, M; D'Andrea, M; Fazio, A; Fenwick, A; Iaccarino, G; Johansson, L; Strigari, L; Ungania, S; De Felice, P

    2016-06-01

    Over the last years (177)Lu has received considerable attention from the clinical nuclear medicine community thanks to its wide range of applications in molecular radiotherapy, especially in peptide-receptor radionuclide therapy (PRRT). In addition to short-range beta particles, (177)Lu emits low energy gamma radiation of 113keV and 208keV that allows gamma camera quantitative imaging. Despite quantitative cancer imaging in molecular radiotherapy having been proven to be a key instrument for the assessment of therapeutic response, at present no general clinically accepted quantitative imaging protocol exists and absolute quantification studies are usually based on individual initiatives. The aim of this work was to develop and evaluate an approach to gamma camera calibration for absolute quantification in tomographic imaging with (177)Lu. We assessed the gamma camera calibration factors for a Philips IRIX and Philips AXIS gamma camera system using various reference geometries, both in air and in water. Images were corrected for the major effects that contribute to image degradation, i.e. attenuation, scatter and dead- time. We validated our method in non-reference geometry using an anthropomorphic torso phantom provided with the liver cavity uniformly filled with (177)LuCl3. Our results showed that calibration factors depend on the particular reference condition. In general, acquisitions performed with the IRIX gamma camera provided good results at 208keV, with agreement within 5% for all geometries. The use of a Jaszczak 16mL hollow sphere in water provided calibration factors capable of recovering the activity in anthropomorphic geometry within 1% for the 208keV peak, for both gamma cameras. The point source provided the poorest results, most likely because scatter and attenuation correction are not incorporated in the calibration factor. However, for both gamma cameras all geometries provided calibration factors capable of recovering the activity in

  20. 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.)

  1. (90) Y/(177) Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Sarma, Haladhar Dev; Nair, K V Vimalnath; Rajeswari, Ardhi; Dash, Ashutosh

    2016-07-01

    Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 ± 0.27 GBq/mg for (90) Y-CHX-A″-DTPA-Cetuximab and 1.14 ± 0.15 GBq/mg for (177) Lu-CHX-A″-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-A″-DTPA-Cetuximab and (177) Lu-CHX-A″-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-A″-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation.

  2. {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.)

  3. Direct no-carrier-added {sup 18}F-labelling of arenes via nucleophilic substitution on aryl(2-thienyl)iodonium salts

    Energy Technology Data Exchange (ETDEWEB)

    Ross, T.L.

    2006-01-15

    For in vivo imaging of molecular processes via positron emission tomography (PET) radiotracers of high specific activity are demanded. In case of the most commonly used positron emitter fluorine-18, this is only achievable with no-carrier-added [{sup 18}F]fluoride, which implies nucleophilic methods of {sup 18}F-substitution. Whereas electron deficient aromatic groups can be labelled in one step using no-carrier-added [{sup 18}F]fluoride, electron rich {sup 18}F-labelled aromatic molecules are only available by multi-step radiosyntheses or carrier-added electrophilic reactions. Here, diaryliodonium salts represent an alternative, since they have been proven as potent precursor for a direct nucleophilic {sup 18}F-introduction into aromatic molecules. Furthermore, as known from non-radioactive studies, the highly electron rich 2-thienyliodonium leaving group leads to a high regioselectivity in nucleophilic substitution reactions. Consequently, a direct nucleophilic no-carrier-added {sup 18}F-labelling of electron rich arenes via aryl(2-thienyl)iodonium precursors was developed in this work. The applicability of direct nucleophilic {sup 18}F-labelling was examined in a systematic study on eighteen aryl(2-thienyl)iodonium salts. As electron rich precursors the ortho-, meta- and para-methoxyphenyl(2-thienyl)iodonium bromides, iodides, tosylates and triflates were synthesised. In addition, para-substituted (R=BnO, CH{sub 3}, H, Cl, Br, I) aryl(2-thienyl)iodonium bromides were prepared as precursors with a systematically varying electron density. As first approach, the general reaction conditions of the nucleophilic {sup 18}F-substitution procedure were optimised. The best conditions for direct nucleophilic no-carrier-added {sup 18}F-labelling via aryl(2-thienyl)iodonium salts were found with dimethylformamide as solvent, a reaction temperature of 130{+-}3 C and 25 mmol/l as concentration of the precursor. (orig.)

  4. No-carrier-added (NCA) aryl [{sup 18}F]fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yu-Shin; Fowler, J.S.; Wolf, A.P.

    1991-12-31

    A method for synthesizing no-carrier-added (NCA) aryl [{sup 18}F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substituent on an electron rich ring. The reaction is carried out by nucleophilic aromatic substitution with a no-carrier-added (NCA) [{sup 18}F]fluoride ion. The method can be used to synthesize various no-carrier-added aryl [{sup 18}F]fluoride compositions, including 6-[{sup 18}F]fluoro-L-DOPA, 2-[{sup 18}F]fluorotyrosine, 6-[{sup 18}F]fluoronorepinephrine, and 6-[{sup 18}F]fluorodopamine. In those instances when a racemic mixture of enantiomers is produced by the present invention, such as in the synthesis of 6-[{sup 18}F]fluoronorepinephrine, a preferred method also includes resolution of the racemic mixture on a chiral HPLC column. This procedure results in a high yield of enantiomerically pure [{sup 18}F] labeled isomers, for example [-]-6-[{sup 18}F]fluoronorepinephrine and [+]-6-[{sup 18}F]fluoronorepinephrine.

  5. 177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice

    Science.gov (United States)

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Giusti, Anna Maria; Riccardi, Elena; Bruland, Øyvind S.; Selbo, Pål Kristian; Dahle, Jostein

    2014-01-01

    Background 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 studieswith 177Lu-HH1. Methodology/Principal Findings 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. Conclusions/Significance 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. PMID:25068508

  6. 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.

  7. 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.

  8. 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.

  9. Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers.

    Science.gov (United States)

    Kameswaran, Mythili; Pandey, Usha; Gamre, Naresh; Vimalnath, K V; Sarma, Haladhar Dev; Dash, Ashutosh

    2016-08-01

    This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  11. 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

  12. 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

  13. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity.C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys. At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a global transcriptional variations in kidney tissues, (b morphological changes in the kidneys, (c changes in white and red blood cell count as well as blood levels of urea, and (d changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months.Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these

  14. A systematic study on the utility of CHX-A''-DTPA-NCS and NOTA-NCS as bifunctional chelators for (177)Lu radiopharmaceuticals.

    Science.gov (United States)

    Pandey, Usha; Gamre, Naresh; Lohar, Sharad Pandurang; Dash, Ashutosh

    2017-09-01

    This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for (177)Lu. While (177)Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of (177)Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of (177)Lu-NOTA-NCS significantly as compared to (177)Lu-CHX-A''-DTPA-NCS. In vitro stability of (177)Lu-CHX-A''-DTPA-NCS was also superior to (177)Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of (177)Lu radiopharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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...... with known activity concentration ratio between the uniform background and filled hollow spheres were acquired for three different collimators: low-energy high resolution (LEHR), low-energy general purpose (LEGP) and medium-energy general purpose (MEGP). Counts were collected in several energy windows......, and scatter correction was performed by applying different methods such as effective scatter source estimation (ESSE), triple-energy and dual-energy window, double-photopeak window and downscatter correction. The intensity ratio between the spheres and the background was measured and corrected for the partial...

  16. Effect of amplified spontaneous emission on selectivity of laser photoionisation of the 177Lu radioisotope

    Science.gov (United States)

    D'yachkov, A. B.; Gorkunov, A. A.; Labozin, A. V.; Mironov, S. M.; Panchenko, V. Ya; Firsov, V. A.; Tsvetkov, G. O.

    2016-06-01

    A significant deselecting effect of amplified spontaneous emission has been observed in the experiments on selective laser photoionisation of the 177Lu radioisotope according to the scheme 5d6s2 2D3/2 → 5d6s6p 4Fo5/2 (18505 cm-1) → 5d6s7s 4D3/2(37194 cm-1) → autoionisation state (53375 cm-1). The effect is conditioned by involvement of non-target isotopes from the lower metastable level 5d6s2 2D5/2(1994 cm-1) into the ionisation process. Spectral filtering of spontaneous emission has allowed us to significantly increase the selectivity of the photoionisation process of the radioisotope and to attain a selectivity value of 105 when using saturating light intensities.

  17. Photon strength functions in 177Lu: Study of scissors resonance in high-spin region

    Directory of Open Access Journals (Sweden)

    Bečvář F.

    2015-01-01

    Full Text Available The nucleus 177Lu is characteristic by an unusually high value of the thermal-neutron capturing state spin, J = 13/2, and by distinct low-energy rotational bands built on the 7/2+ ground state and the 9/2− level at 150 keV. The γ cascades connecting the capturing state with the members of these bands carry unique information about the role of identical M1 scissors-mode resonances, built according to Brink hypothesis assumingly on each energy level, even in conditions of fast nuclear rotation. With this motivation we measured a set of spectra of two-step γ cascades following the thermal neutron capture in 176Lu. The measurement was performed at neutron beam of the LWR-15 Reactor in Řež. From the analysis of these spectra the common parameters of the scissors resonances were deduced. The obtained results are discussed.

  18. Anti-EGFRvIII monoclonal antibody armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Zhao Xiaoguang [Department of Radiology, 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., E-mail: zalut001@mc.duke.ed [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)

    2010-10-15

    Introduction: Monoclonal antibody (mAb) L8A4 binds specifically to the epidermal growth factor receptor variant III (EGFRvIII) that is present on gliomas but not on normal tissues, and is internalized rapidly after receptor binding. Because of the short range of its {beta}-emissions, labeling this mAb with {sup 177}Lu would be an attractive approach for the treatment of residual tumor margins remaining after surgical debulking of brain tumors. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1, 2-diamine-pentaacetic acid (CHX-A''-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylene-triaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label tissue distribution experiments were performed in athymic mice bearing subcutaneous EGFRvIII-expressing U87.{Delta}EGFR glioma xenografts over a period of 1 to 8 days to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). Results: Except with C-DOTA, tumor uptake for the {sup 177}Lu-labeled mAb was significantly higher than the co-administered radioiodinated preparation; however, this was also the case for spleen, liver, bone and kidneys. Tumor/normal tissue ratios for {sup 177}Lu-1B4M-DTPA-L8A4 and, to an even greater extent, {sup 177}Lu-MeO-DOTA-L8A4 were higher than those for [{sup 125}I]SGMIB-L8A4 in most other tissues. Conclusions: Tumor and normal tissue distribution patterns for this anti-EGFRvIII mAb were dependent on the nature of the bifunctional chelate used for {sup 177}Lu labeling. Optimal results were obtained with 1B4M-DTPA and MeO-DOTA, suggesting no clear advantage

  19. 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.

  20. Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, Bart de; Kam, Boen L.R.; Essen, Martijn van; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam, P.O. Box 2040 (Netherlands); Aken, Maarten O. van; Feelders, Richard A.; Herder, Wouter W. de [Erasmus Medical Center, Section of Endocrinology, Department of Internal Medicine, Rotterdam (Netherlands)

    2008-04-15

    Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate). All {sup 177}Lu-octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included for analysis. Four hundred seventy-nine patients received a total of 1,693 administrations of {sup 177}Lu-octreotate. Six of 479 patients (1%) developed severe symptoms because of massive release of bioactive substances after the first cycle of {sup 177}Lu-octreotate. One patient had a metastatic hormone-producing small intestinal carcinoid; two patients had metastatic, hormone-producing bronchial carcinoids; two patients had vasoactive intestinal polypeptide-producing pancreatic endocrine tumors (VIPomas); and one patient had a metastatic pheochromocytoma. With adequate treatment, all patients eventually recovered. Hormonal crises after {sup 177}Lu-octreotate therapy occur in 1% of patients. Generally, {sup 177}Lu-octreotate therapy is well tolerated. (orig.)

  1. 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)

  2. Separation of no-carrier-added {sup 66,67}Ga produced in heavy ion-induced cobalt target using alginate biopolymers

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Dalia [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 (India); Banerjee, Anupam [University of Calcutta, 35 Ballygunge Circular Road, Kolkata-700019 (India); Lahiri, Susanta [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata-700064 (India)]. E-mail: susanta.lahiri@saha.ac.in

    2007-08-15

    Heavy ion activation of natural cobalt foil with 84 MeV {sup 12}C results in the formation of no-carrier-added (nca) {sup 66,67}As radionuclides, along with their corresponding decay products, {sup 66,67}Ge and {sup 66,67}Ga, in the matrix. Because arsenic and germanium radionuclides are short-lived, after a cooling period of 10 h only nca gallium radionuclides remain in the matrix. We attempted to separate the nca gallium radionuclides from the target matrix cobalt by biopolymeric calcium alginate (CA) and Fe-doped calcium alginate (Fe-CA) beads. A complete separation has been achieved by adsorbing {sup 66,67}Ga and a lesser amount of bulk cobalt at pH 3 on Fe-CA beads, followed by desorbing cobalt from the beads with 0.4 M NaNO{sub 2}.

  3. 177Lu-DTPA-BIS-BIOTIN的制备及正常鼠体内生物分布%Preparation of 177Lu-DTPA-BIS-BIOTIN and Biodistribution Evaluation in Normal Mice

    Institute of Scientific and Technical Information of China (English)

    邓新荣; 杜进; 罗志福

    2010-01-01

    研究了DTPA-BIS-BIOTIN的177Lu标记方法,优化了标记条件,并进行了标记物在正常小鼠体内分布实验.在最佳标记条件下(DTPA-BIS-BIOTIN 25 μg,标记介质pH=4.5,80℃反应20 min),177Lu-DTPA-BIS-BIOTIN标记率大于99.0%,室温下放置96 h,标记物体外稳定性良好.正常小鼠体内分布实验结果表明,177Lu-DTPA-BIS-BIOTIN在血液中清除快,主要浓集于肝、脾和肾,经肾脏排泄.本研究为进一步采用177Lu-DTPA-BIS-BIOTIN进行肿瘤预定位显像及治疗研究提供了实验基础.

  4. Therapeutic Efficacy with Treatment-related Toxicities of {sup 177}Lu-labeled Bombesin Derivative for the Peptide Receptor Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Cheong; Cho, Eun Ha; Lee, So Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    The gastrin-releasing peptide receptor (GRPR) has been shown to be overexpressed in many human tumours, including breast cancer, prostate cancer, small cell lung cancer, ovarian cancers, endometrial cancers, and gastrointestinal stromal tumors. In particular, GRPR expression is high in 83 % of invasive primary prostatic carcinomas. These results suggest that {sup 177}Lu-labeled bombesin derivative has promising characteristics as a novel nuclear medicine, especially for the treatment of GRPR over-expressing prostate tumors.

  5. 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.

  6. 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.)

  7. Distinct microRNA expression profiles in mouse renal cortical tissue after 177Lu-octreotate administration.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The aim of this study was to investigate the variation of the miRNA expression levels in normal renal cortical tissue after 177Lu-octreotate administration, a radiopharmaceutical used for treatment of neuroendocrine cancers.Female BALB/c nude mice were i.v. injected with 1.3, 3.6, 14, 45, or 140 MBq 177Lu-octreotate, while control animals received saline. The animals were killed at 24 h after injection and total RNA, including miRNA, was extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo chip 4plex to identify differentially regulated miRNAs between exposed and control samples.In total, 57 specific miRNAs were differentially regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively. No miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090, and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects on cellular mechanisms ranging from immune response to p53 signaling and cancer-related pathways were observed at the highest absorbed dose. Thirty-nine of the 57 differentially regulated miRNAs identified in the present study have previously been associated with response to ionizing radiation, indicating common radiation responsive pathways.In conclusion, the 177Lu-octreotate associated miRNA signatures were generally dose-specific, thereby illustrating transcriptional regulation of radiation responsive miRNAs. Taken together, these results imply the importance of miRNAs in early immunological responses in the kidneys following 177Lu-octreotate administration.

  8. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, Christof; Zoeckler, Christine; Beck, Roswitha; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Quintanilla-Martinez, Leticia [Universitaetsklinikum Tuebingen, Institute for Pathology, Tuebingen (Germany); Bruchertseifer, Frank [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2011-02-15

    {sup 213}Bi-d9MAb-immunoconjugates targeting gastric cancer cells have effectively cured peritoneal carcinomatosis in a nude mouse model following intraperitoneal injection. Because the {beta}-emitter {sup 177}Lu has proven to be beneficial in targeted therapy, {sup 177}Lu-d9MAb was investigated in this study in order to compare its therapeutic efficacy and toxicity with those of {sup 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 {sup 177}Lu-d9MAb immunoconjugates targeting d9-E-cadherin or with nonspecific {sup 177}Lu-d8MAb. Therapeutic efficacy was evaluated by monitoring survival for up to 250 days. For evaluation of toxicity, both biodistribution of {sup 177}Lu-d9MAb and blood cell counts were determined at different time points and organs were examined histopathologically. Treatment with {sup 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 {sup 177}Lu-d9MAb conjugates were superior to nonspecific {sup 177}Lu-d8MAb. Treatment with 7.4 MBq of {sup 177}Lu-d9MAb was most successful, with 90% of the animals surviving longer than 250 days. However, treatment with therapeutically effective activities of {sup 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 {sup 213}Bi-d9MAb at comparable therapeutic efficacy. The therapeutic efficacy of {sup 177}Lu-d9MAb conjugates in peritoneal carcinomatosis is impaired by toxic side effects. Because previous therapy with {sup 213}Bi-d9MAb revealed comparable therapeutic efficacy without toxicity it should be preferred for the treatment of peritoneal carcinomatosis. (orig.)

  10. {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.)

  11. 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.)

  12. 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

  13. 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.

  14. 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)

  15. Automated radiosynthesis of no-carrier-added 4-[18F]fluoroiodobenzene: a versatile building block in 18F radiochemistry.

    Science.gov (United States)

    Way, Jenilee Dawn; Wuest, Frank

    2014-02-01

    4-[18F]Fluoroiodobenzene ([18F]FIB) is a versatile building block in 18F radiochemistry used in various transition metal-mediated C-C and C-N cross-coupling reactions and [18F]fluoroarylation reactions. Various synthesis routes have been described for the preparation of [18F]FIB. However, to date, no automated synthesis of [18F]FIB has been reported to allow access to larger amounts of [18F]FIB in high radiochemical and chemical purity. Herein, we describe an automated synthesis of no-carrier-added [18F]FIB on a GE TRACERlab™ FX automated synthesis unit starting from commercially available(4-iodophenyl)diphenylsulfonium triflate as the labelling precursor. [18F]FIB was prepared in high radiochemical yields of 89 ± 10% (decay-corrected, n = 7) within 60 min, including HPLC purification. The radiochemical purity exceeded 95%, and specific activity was greater than 40 GBq/μmol. Typically, from an experiment, 6.4 GBq of [18F]FIB could be obtained starting from 10.4 GBq of [18F]fluoride.

  16. Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-{sup 11}C]propionyl L-carnitine for pharmacokinetic studies

    Energy Technology Data Exchange (ETDEWEB)

    Davenport, R.J.; Pike, V.W.; Dowsett, K.; Turton, D.R.; Poole, K. [Hammersmith Hospital, London (United Kingdom). MRC Cyclotron Unit

    1997-07-30

    Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t{sub 1/2} = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [{sup 11}C]propionyl chloride as labelling agent via {sup 11}C-carboxylation of ethylmagnesium bromide with cyclotron-produced [{sup 11}C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [{sup 11}C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [{sup 11}C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [{sup 11}C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier added (NCA) level of specific radioactivity. [{sup 11}C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [{sup 11}C]carbon dioxide and hydrolysis. NCA [{sup 11}C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [{sup 11}C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [{sup 11}C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [{sup 11}C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [{sup 11}C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [{sup 11}C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo. (Author).

  17. 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)

  18. 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.

  19. 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.)

  20. Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.

    Science.gov (United States)

    Drerup, Christian; Ermert, Johannes; Coenen, Heinz H

    2016-09-01

    Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies.

  1. 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)

  2. 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.)

  3. Preparation and preliminary studies on {sup 177}Lu-labeled hydroxyapatite particles for possible use in the therapy of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sudipta; Das, Tapas [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Sarma, Haladhar D. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Venkatesh, Meera [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Banerjee, Sharmila [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)], E-mail: sharmila@barc.gov.in

    2008-07-15

    Introduction: Intra-arterial administration of particulates labeled with suitable {beta}{sup -}-emitting radionuclides has emerged as one of the most successful modality for the treatment of primary and metastatic liver cancer. {sup 177}Lu [T{sub 1/2}=6.73 d, E{sub {beta}}(max)=0.49 MeV, E{sub {gamma}}=208 keV (11%)] could be envisaged as a viable radionuclide for use in liver cancer therapy with wider acceptability owing to its feasibility of production in large-scale and relatively longer half-life providing logistic advantages. Hydroxyapatite (HA) particles of 20-60 {mu}m size range are chosen as the particulate carrier due to its excellent biocompatibility and ease of labeling with lanthanides. Methods: {sup 177}Lu was produced by thermal neutron bombardment on enriched Lu target. HA particles of desired size range were synthesized and characterized. Radiolabeling of HA particles was achieved at room temperatures within 30 min. The biological behavior of {sup 177}Lu-labeled HA particles prepared under optimized conditions was tested in Wistar rats. Results: {sup 177}Lu was produced with a specific activity of 444.2{+-}41.8 GBq/mg and radionuclidic purity of 99.98%. {sup 177}Lu-HA was prepared with high radiochemical purity of >99%, and the radiolabeled agent showed excellent in vitro stability. The agent exhibited {approx}73% retention of injected activity in liver after 14 days postadministration with insignificant uptake in any other major organ/tissue except skeleton in biodistribution and imaging studies. Conclusion: {sup 177}Lu-HA exhibited promising features in radiochemical studies. However, preliminary biodistribution studies in normal Wistar rats exhibited suboptimum liver retention and an undesirable skeletal uptake.

  4. 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.

  5. Labeling internalizing anti-epidermal growth factor receptor variant III monoclonal antibody with {sup 177}Lu: in vitro comparison of acyclic and macrocyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Welsh, Phil [Department of Radiology, 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

    2009-02-15

    Introduction: The monoclonal antibody (mAb) L8A4, reactive with the epidermal growth factor receptor variant III (EGFRvIII), internalizes rapidly in glioma cells after receptor binding. Combining this tumor-specific mAb with the low-energy {beta}-emitter {sup 177}Lu would be an attractive approach for brain tumor radioimmunotherapy, provided that trapping of the radionuclide in tumor cells after mAb intracellular processing could be maximized. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S) -cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA), 2-(4-isothiocyanatobenzyl)-diethylenetriaminepenta-acetic acid (pSCN-Bz-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label internalization and cellular processing assays were performed on EGFRvIII-expressing U87.{delta}EGFR glioma cells over 24 h to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using either iodogen or N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). In order to facilitate comparison of labeling methods, the primary parameter evaluated was the ratio of {sup 177}Lu to {sup 125}I activity retained in U87.{delta}EGFR cells. Results: All chelates demonstrated higher retention of internalized activity compared with mAb labeled using iodogen, with {sup 177}Lu/{sup 125}I ratios of >20 observed for the three DTPA chelates at 24 h. When compared to L8A4 labeled using SGMIB, except for MeO-DOTA, internalized activity for {sup 125}I was higher than {sup 177}Lu from 1-8 h with the opposite behavior observed thereafter. At 24 h, {sup 177}Lu/{sup 125}I ratios were between 1

  6. 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

  7. Renal function affects absorbed dose to the kidneys and haematological toxicity during {sup 177}Lu-DOTATATE treatment

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Johanna; Berg, Gertrud [Sahlgrenska University Hospital, Department of Oncology, Goeteborg (Sweden); Waengberg, Bo [Sahlgrenska University Hospital, Department of Surgery, Goeteborg (Sweden); Larsson, Maria [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Forssell-Aronsson, Eva; Bernhardt, Peter [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengineering, Goeteborg (Sweden)

    2015-05-01

    Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment. The study included 51 patients with an advanced neuroendocrine tumour who received {sup 177}Lu-DOTATATE treatment during 2006 - 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 - 8.2 GBq) was given at intervals of 6 - 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated. A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of {sup 177}Lu in the whole body (range 0.89 - 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53). Patients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during {sup 177}Lu-DOTATATE treatment. The study confirms the

  8. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with {sup 177}Lu-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [Charite, University Medicine Berlin, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Berlin (Germany); Nagarajah, James [University Hospital, Department of Nuclear Medicine, Essen (Germany)

    2014-03-15

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with {sup 177}Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by {sup 99m}Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m{sup 2} per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m{sup 2} per year) and 16 patients (22 %) a significant (>10 ml/min/m{sup 2} per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m{sup 2} per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of

  9. 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.)

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-11-15

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

  12. Outcome and toxicity of salvage therapy with {sup 177}Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Haslerud, Torjan; Sabet, Amin; Ahmadzadehfar, Hojjat; Guhlke, Stefan; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [University Medicine Berlin, Department of Hepatology and Gastroenterology, Charite, Campus Virchow Clinic, Berlin (Germany); Gruenwald, Frank [University Hospital, Department of Nuclear Medicine, Frankfurt (Germany)

    2014-02-15

    We assessed the outcome and toxicity of salvage therapy (repeat treatment) with {sup 177}Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET). We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0-83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p < 0.05. Radiographic responses consisted of complete response in 1 patient (3.0 %), partial response in 6 patients (18.2 %), minor response in 1 patient (3.0 %), stable disease in 14 patients (42.4 %), and progressive disease in 11 patients (33.3 %). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95 % CI 9-18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p = 0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2 %). The cumulative administered activity was not associated with an increased incidence of haematotoxicity. PRRT with {sup 177}Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET. (orig.)

  13. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.

    NARCIS (Netherlands)

    Brouwers, A.H.; Eerd-Vismale, J.E.M. van; Frielink, C.; Oosterwijk, E.; Oyen, W.J.G.; Corstens, F.H.M.; Boerman, O.C.

    2004-01-01

    Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with

  14. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.

    NARCIS (Netherlands)

    Brouwers, A.H.; Eerd-Vismale, J.E.M. van; Frielink, C.; Oosterwijk, E.; Oyen, W.J.G.; Corstens, F.H.M.; Boerman, O.C.

    2004-01-01

    Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with

  15. An approach for conjugation of 177 Lu- DOTA-SCN- Rituximab (BioSim & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients

    Directory of Open Access Journals (Sweden)

    Parul Thakral

    2014-01-01

    Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim in patients of relapsed and refractory non Hodgkin′s lymphoma can be considered.

  16. 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.

  17. 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

  18. DOTA conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice.

    Science.gov (United States)

    Müller, Cristina; Struthers, Harriet; Winiger, Christian; Zhernosekov, Konstantin; Schibli, Roger

    2013-01-01

    The folate receptor (FR) has proven a valuable target for nuclear imaging using folic acid radioconjugates. However, using folate-based radiopharmaceuticals for therapy has long been regarded as an unattainable goal because of their considerable renal accumulation. Herein, we present a novel strategy in which a DOTA-folate conjugate with an albumin-binding entity (cm09) was designed with the aim of prolonging circulation in the blood and therewith potentially improving tumor-to-kidney ratios. The folate conjugate cm09 was radiolabeled with (177)LuCl(3), and stability experiments were performed in plasma. Cell uptake studies were performed on FR-positive KB tumor cells, and an ultrafiltration assay was used to determine the plasma protein-binding properties of (177)Lu-cm09. In vivo, (177)Lu-cm09 was tested in KB tumor-bearing mice using SPECT/CT. The therapeutic anticancer effect of (177)Lu-cm09 (20 MBq) applied as a single injection or as fractionated injections was investigated in different groups of mice (n = 5) by monitoring tumor size and the survival time of treated mice, compared with untreated controls. Compound cm09 was radiolabeled at a specific activity of 40 MBq/nmol, a radiochemical yield of more than 98%, and a stability of more than 99% over 5 d in plasma. Ultrafiltration revealed significant binding of (177)Lu-cm09 to serum proteins (∼91%) in plasma, compared with folate radioconjugate without an albumin-binding entity. Cell uptake and internalization of (177)Lu-cm09 was FR-specific and comparable to other folate radioconjugates. In vivo studies resulted in high tumor uptake (17.56 percentage injected dose per gram [%ID/g] at 4 h after injection), which was almost completely retained for at least 72 h. Renal accumulation was significantly reduced (28 %ID/g at 4 h after injection), compared with folate conjugates that lack an albumin-binding entity (∼70 %ID/g at 4 h after injection). These circumstances enabled SPECT imaging of excellent quality

  19. Preparation and Preliminary Biological Evaluation of {sup 177}Lu-DOTA folate as Potential Folate Receptor Targeting Therapeutic Agent

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kang-Hyuk; Hong, Young-Don; Pyun, Mi-Sun; Lee, So-Young; Felipe, Fenelope; Yoon, Sun-Ha; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-10-15

    Folic Acid (FA) and FA derivatives are overexpressed on several tumor cells. The cell-membrane folic acid receptors are known to be responsible for the cellular accumulation of FA and FA analogs, such as methotrexate and folic acid. Folate has been characterized to have high affinity for the folate-receptor positive cells and tissues and considered to be useful as diagnostic imaging and therapeutic agent. In 1940s, Folate analogue, aminopterin, was first used for treatment of leukemia and recently, many folate derivatives were tried for cancer-treatment agent as well as visualization of folate receptor. Many researchers tried to conjugate folic acid with macromolecules or low molecular weight chelators through its alpha or gamma carboxylate. However, despite the reduced binding affinity, FAs are still recognized by the folate receptor. Therefore, we focused to develop folate-based radiopharmaceutical that has the potential to be used as a therapeutic agent. We report here the synthesis and the radiolabeling of {sup 177}Lu-DOTA as well as the biodistribution data of our developed compound.

  20. 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

  1. 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....... Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. RESULTS: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with 211At-labeled antibodies did not reduce the proportion of animals developing metastases...

  2. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2012-09-01

    al., “The effects of induced hypogonadism on arterial stiffness , body composi- tion, and metabolic parameters in males with prostate cancer ,” The...Phase 2 Trial of 177Lu Radiolabeled Monoclonal Antibody J591in Patients with High-Risk Castrate Biochemically Relapsed Prostate Cancer PRINCIPAL...NUMBER in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer 5b. GRANT NUMBER W81XWH-09-1-0596 5c. PROGRAM ELEMENT NUMBER

  3. 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)

  4. 奥曲肽-葡聚糖-亲和素的偶联及其与177Lu-DTPA-BIS-BIOTIN的体外结合%177Lu-DTPA-BIS-BIOTIN Binding of Octreotide-dextran-avidinated PANC-1 Cell Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    邓新荣; 杜进; 翟士桢; 沈亦佳; 罗志福

    2011-01-01

    以葡聚糖为载体,奥曲肽为导向分子合成了生长抑素配体化合物奥曲肽-葡聚糖-亲和素(Tyr3-oct-reotide-dxtran 40-avidin,TOC-Dx40-Av);在体外模拟肿瘤预定位二步法以177Lu-DTPA-BIS-BIOTIN对TOC-Dx40-Av培养的PANC-1细胞的结合特性进行了研究.将长满人源胰腺癌细胞PANC-1的24孔板置于含有TOC-Dx40-Av的缓冲液中培养,2h后洗去上清液,再用含不同浓度177Lu- DTPA-BIS-BIOTIN(177Lu-DT-PA-BIS-BIOTIN的摩尔质量范围为48.8~391 pmol)的缓冲液继续培养细胞,使177Lu-DTPA-BIS-BIOTIN 与细胞上的亲和素结合,测定细胞上结合的放射性计数,考察TOC-Dx40-Av与177 Lu-DTPA-BIS-BIOTIN的结合特性以评价合成的大分子亲和素连接物的活性.实验结果显示,奥曲肽-葡聚糖-亲和素的化学纯度>99%,其中亲和素的含量为6.46 g/L.体外细胞结合实验结果表明,177Lu-DTPA-BIS-BIOTIN能快速与细胞上连接的亲和素结合,生物素与亲和素的摩尔比约为1∶1达到平衡.%Tyr3-octreotide, dextran-40 and avidin were used to prepare octreotide-dextran-avidin (TOC-Dx40-Av). DTPA-BIS-BIOTIN was labelled with 177Lu. The in vitro soma-tostatin receptor binding study was carried out by pretargeted method using TOC-Dx40-Av and 177Lu-DTPA-BIS-BIOTIN. The 24 well cell culture plates were prepared with PANC-1 cell monolayer and then incubated with TOC-Dx40-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 y counter. The results showed that the chemi- cal purity of TOC-Dx40-Av was over 99%. The results also showed that TOC-Dx40-Av remained high receptor binding affinity to somatostatin receptor which indicated that TOC-Dx40-Av could bind to 177 Lu-DTPA-BIS-BIOTIN with the molar ratio of 1 ? 1 on the cell surface.

  5. {sup 177}Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity {sup 111}In-octreotide

    Energy Technology Data Exchange (ETDEWEB)

    Hubble, Daniel; Kong, Grace; Michael, Michael; Johnson, Val; Ramdave, Shakher; Hicks, Rodney John [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, East Melbourne, VIC (Australia)

    2010-10-15

    The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity {sup 111}In-pentetreotide can be safely treated with {sup 177}Lu-octreotate and whether addition of radiosensitising chemotherapy increases the toxicity of this agent. Records of 27 patients (aged 17-75) who received 69 (median 3 per patient) {sup 177}Lu-octreotate administrations, including 29 in conjunction with radiosensitising infusional 5-fluorouracil (5-FU) (n = 27), or capecitabine (n = 2), between October 2005 and July 2007 subsequent to 1-8 prior cycles of {sup 111}In-pentetreotide therapy were analysed. Toxicity was assessed during and at 8-12 weeks post-treatment, with further long-term assessments including survival status reviewed till death or study close-out date of 1 November 2009. Reduction in blood counts was most marked following the first dose of {sup 177}Lu-octreotate but at early follow-up the only major haematological toxicity was a single case of grade 4 lymphopaenia. Both the presence of bone metastases and the administration of chemotherapy tended to result in greater reduction in blood counts, but these differences did not reach statistical significance. On long-term follow-up, 16 patients (59%) are alive with median overall survival of 36 months (32-44 months from first {sup 177}Lu-octreotate therapy). None of the recorded deaths was directly related to treatment toxicity. One patient had late grade 4 anaemia and thrombocytopaenia secondary to bone marrow failure from progressive infiltration by tumour. No other significant long-term haematological toxicities were recorded and no leukaemia was observed. No renal toxicity was observed on serial serum creatinine or radionuclide glomerular filtration rate (GFR) determination on initial or long-term follow-up. {sup 177}Lu-octreotate is a safe and well-tolerated therapy for patients who have previously been treated with {sup 111}In-pentetreotide and can

  6. {sup 177}Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Krishan Kant; Singla, Suhas; Arora, Geetanjali; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India)

    2015-01-15

    The purpose of this study was to evaluate the efficacy and safety of {sup 177}Lu-EDTMP for pain palliation in patients with bone metastases from castration-resistant prostate and breast cancer. The secondary objective was to compare low-dose and high-dose {sup 177}Lu-EDTMP in bone pain palliation. Included in the study were 44 patients with documented breast carcinoma (12 patients; age 47 ± 13 years) or castration-resistant prostate carcinoma (32 patients; age 66 ± 9 years) and skeletal metastases. Patients were randomized into two equal groups treated with {sup 177}Lu-EDTMP intravenously at a dose of 1,295 MBq (group A) or 2,590 MBq (group B). Pain palliation was evaluated using a visual analogue score (VAS), analgesic score (AS) and Karnofsky performance score (KPS) up to 16 weeks. Toxicity was assessed in terms of haematological and renal parameters. The overall response rate (in all 44 patients) was 86 %. Complete, partial and minimal responses were seen in 6 patients (13 %), 21 patients (48 %) and 11 patients (25 %), respectively. A favourable response was seen in 27 patients (84 %) with prostate cancer and in 11 patients (92 %) with breast cancer. There was a progressive decrease in the VAS from baseline up to 4 weeks (p < 0.05). Also, AS decreased significantly from 1.8 ± 0.7 to 1.2 ± 0.9 (p < 0.0001). There was an improvement in quality of life of the patients as reflected by an increase in mean KPS from 56 ± 5 to 75 ± 7 (p < 0.0001). The overall response rate in group A was 77 % compared to 95 % in group B (p = 0.188). There was a significant decrease in VAS and AS accompanied by an increase in KPS in both groups. Nonserious haematological toxicity (grade I/II) was observed in 15 patients (34 %) and serious toxicity (grade III/IV) occurred in 10 patients (23 %). There was no statistically significant difference in haematological toxicity between the groups. {sup 177}Lu-EDTMP was found to be a safe and effective radiopharmaceutical for bone pain

  7. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Giovanni; Sansovini, Maddalena; Ambrosetti, Alice; Severi, Stefano; Ianniello, Annarita; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola, FC (Italy); Monti, Manuela; Scarpi, Emanuela [IRST IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Donati, Caterina [IRST IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Amadori, Dino [IRST IRCCS, Department of Medical Oncology, Meldola (Italy)

    2014-10-15

    We evaluated the activity and safety profile of {sup 177}Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs). Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan registered completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve. Twenty-five (58 %) patients were treated with a ''standard'' Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT. Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity. (orig.)

  8. 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

  9. Excitation function for deuteron induced nuclear reactions on natural ytterbium for production of high specific activity {sup 177g}Lu in no-carrier-added form for metabolic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Manenti, Simone, E-mail: simone.manenti@mi.infn.i [LASA, Universita degli Studi di Milano and INFN-Milano, via F.lli Cervi 201, I-20090 Segrate (Italy); Groppi, Flavia; Gandini, Andrea; Gini, Luigi [LASA, Universita degli Studi di Milano and INFN-Milano, via F.lli Cervi 201, I-20090 Segrate (Italy); Abbas, Kamel; Holzwarth, Uwe; Simonelli, Federica [Institute for Health and Consumer Protection, Joint Research Centre, European Commission, TP 500, I-21020 Ispra (Italy); Bonardi, Mauro, E-mail: mauro.bonardi@mi.infn.i [LASA, Universita degli Studi di Milano and INFN-Milano, via F.lli Cervi 201, I-20090 Segrate (Italy)

    2011-01-15

    Deuteron-induced nuclear reactions for generation of no-carrier-added Lu radionuclides were investigated using the stacked-foil activation technique on natural Yb targets at energies up to E{sub d}=18.18 MeV. Excitation functions of the reactions {sup nat}Yb(d,xn){sup 169,170,171,172,173,174g,174m,176m,177g}Lu and {sup nat}Yb(d,pxn){sup 169,175,177}Yb have been measured, among them three ({sup 169}Lu, {sup 174m}Lu and {sup 176m}Lu) are reported for the first time. The upper limit of the contamination from the long-lived metastable level {sup 177m}Lu was evaluated too. Thick-target yields for all investigated radionuclides are calculated.

  10. Multimodal Somatostatin Receptor Theranostics Using [64Cu]Cu-/[177Lu]Lu-DOTA-(Tyr3)octreotate and AN-238 in a Mouse Pheochromocytoma Model

    Science.gov (United States)

    Ullrich, Martin; Bergmann, Ralf; Peitzsch, Mirko; Zenker, Erik F.; Cartellieri, Marc; Bachmann, Michael; Ehrhart-Bornstein, Monika; Block, Norman L.; Schally, Andrew V.; Eisenhofer, Graeme; Bornstein, Stefan R.; Pietzsch, Jens; Ziegler, Christian G.

    2016-01-01

    Pheochromocytomas and extra-adrenal paragangliomas (PHEO/PGLs) are rare catecholamine-producing chromaffin cell tumors. For metastatic disease, no effective therapy is available. Overexpression of somatostatin type 2 receptors (SSTR2) in PHEO/PGLs promotes interest in applying therapies using somatostatin analogs linked to radionuclides and/or cytotoxic compounds, such as [177Lu]Lu-DOTA-(Tyr3)octreotate (DOTATATE) and AN-238. Systematic evaluation of such therapies for the treatment of PHEO/PGLs requires sophisticated animal models. In this study, the mouse pheochromocytoma (MPC)-mCherry allograft model showed high tumor densities of murine SSTR2 (mSSTR2) and high tumor uptake of [64Cu]Cu-DOTATATE. Using tumor sections, we assessed mSSTR2-specific binding of DOTATATE, AN-238, and somatostatin-14. Therapeutic studies showed substantial reduction of tumor growth and tumor-related renal monoamine excretion in tumor-bearing mice after treatment with [177Lu]Lu-DOTATATE compared to AN-238 and doxorubicin. Analyses did not show agonist-dependent receptor downregulation after single mSSTR2-targeting therapies. This study demonstrates that the MPC-mCherry model is a uniquely powerful tool for the preclinical evaluation of SSTR2-targeting theranostic applications in vivo. Our findings highlight the therapeutic potential of somatostatin analogs, especially of [177Lu]Lu-DOTATATE, for the treatment of metastatic PHEO/PGLs. Repeated treatment cycles, fractionated combinations of SSTR2-targeting radionuclide and cytotoxic therapies, and other adjuvant compounds addressing additional mechanisms may further enhance therapeutic outcome. PMID:27022413

  11. Peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Bakker, Willem H.; Kwekkeboom, Dik J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Aken, Maarten O. van [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2007-08-15

    Foregut carcinoid tumours have a different embryological origin than other gastroenteropancreatic neuroendocrine tumours (GEP NETs). In the total group of GEP NETs (n = 131), treatment with {sup 177}Lu-octreotate resulted in tumour remission in 47% of patients, with a median time to progression (TTP) of >36 months. As patients with foregut carcinoids may respond differently, we here present the effects of this treatment in a subgroup of patients with foregut carcinoids of bronchial, gastric or thymic origin. Nine patients with bronchial, five with gastric and two with thymic carcinoids were treated. All patients had metastasised disease. The intended cumulative dose of {sup 177}Lu-octreotate was 22.2-29.6 GBq. Southwest Oncology Group criteria were used for response evaluation. Bronchial carcinoids: Five patients had partial remission, one had minor response (MR, tumour size reduction: {>=}25%, <50%), two had stable disease (SD) and one had progressive disease (PD). Median TTP was 31 months. Gastric carcinoids: One patient had complete remission, one had MR and two had SD, including one with PD at baseline. One patient developed PD. Thymic carcinoids: One patient had SD. In the other patient, disease remained progressive. All patients: Overall remission rate was 50%, including MR. {sup 177}Lu-octreotate treatment can be effective in patients with bronchial and gastric carcinoids. Its role in thymic carcinoids cannot be determined yet because of the limited number of patients. The overall remission rate of 50% in patients with the studied foregut carcinoids is comparable to that in the total group of GEP NETs. (orig.)

  12. 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

  13. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Kwekkeboom, D.J.; Bakker, W.H.; Kam, B.L.; Teunissen, J.J.M.; Kooij, P.P.M.; Jong, M. de [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Herder, W.W. de; Feelders, R.A. [Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands); Eijck, C.H.J. van [Department of Surgery, Erasmus Medical Center, Rotterdam (Netherlands); Srinivasan, A.; Erion, J.L. [Mallinckrodt Medical, St. Louis, Missouri (United States); Krenning, E.P. [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands)

    2003-03-01

    Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [{sup 90}Y-DOTA{sup 0},Tyr{sup 3}]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA{sup 0},Tyr{sup 3}]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA{sup 0},Tyr{sup 3}]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide {sup 177}Lu, it has proved very successful in achieving tumour regression in animal models. The effects of {sup 177}Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi {sup 177}Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours

  14. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Wu, Yin; Pfeifer, Andreas Klaus; Myschetzky, Rebecca;

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising...... clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following...

  15. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2014-09-01

    ates such as choline, citric acid , and certain lipids that are powerful biomarkers for aggressive disease. More recently, with support from the PCRP...flow-cytometry. Glial-derived MP (GFAP+) were measured using anti-glial fibrillary acidic protein (GFAP)-FITC and TF-bearing (TF+ MP) using anti-CD142...fractionated doses of 177Lu-J591 (initial dose 20 mCi/m2 x2 up to max of 40 mCi/m2 x2) with cycle 3. Cycle 4 of docetaxel was planned 6 weeks after

  16. Development of {sup 177}Lu-DTPA-SPIO conjugates for potential use as a dual contrast SPECT/MRI imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Shanehsazzadeh, Saeed; Yousefnia, Hassan [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Gruettner, Cordula [Micromod Partikeltechnologie GmbH, Rostock (Germany); and others

    2016-08-01

    This study describes the preparation, biodistribution of {sup 177}Lu-DTPA-SPIO after intravenous injection in rats. The chelator DTPA dianhydride was conjugated to SPIO NPs using a small modification of the well-known cyclic anhydride method. Conjugation was done at a 1:2 (SPIO:ccDTPA) molar ratio. Conjugation reaction was purified with Magnetic assorting column (MACs) using high gradient magnetic field following incubation, the radio labeled conjugate was checked using RTLC method for labeling and purity checked. The RTLC showed that labeling yield was above 99% after purification and the compound have good in-vitro stabilities until 48 h post injection in the presence of human serum. The biodistribution of {sup 177}Lu-DTPA-SPIO in rats showed dramatic uptake in the reticuloendothelial system (RES) and their clearance is so fast in other organs especially in the blood. In conclusion, due to high uptakes of this radiotracer in the liver and spleen and their fast clearance from other tissues, especially in blood, it is suggested that this radiotracer would be suitable for RES studies.

  17. Individualized dosimetry in patients undergoing therapy with {sup 177}Lu-DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sandstroem, Mattias [Uppsala University Hospital, Department of Oncology, Radiology and Clinical Immunology, Division of Medical Physics, Uppsala (Sweden); Uppsala University Hospital, Department of Hospital Physics, Uppsala (Sweden); Garske, Ulrike [Uppsala University Hospital, Department of Medical Sciences, Division of Nuclear Medicine, Uppsala (Sweden); Granberg, Dan [Uppsala University Hospital, Department of Medical Sciences, Division of Endocrine Oncology, Uppsala (Sweden); Sundin, Anders [Karolinska University Hospital, Department of Molecular Medicine and Surgery, Division of Diagnostic Radiology, Stockholm (Sweden); Lundqvist, Hans [Uppsala University, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden)

    2010-02-15

    In recent years, targeted radionuclide therapy with [{sup 177}Lu-DOTA{sup 0}, Tyr{sup 3}]octreotate for neuroendocrine tumours has yielded promising results. This therapy may be further improved by using individualized dosimetry allowing optimization of the absorbed dose to the tumours and the normal organs. The aim of this study was to investigate the feasibility and reliability of individualized dosimetry based on SPECT in comparison to conventional planar imaging. Attenuation-corrected SPECT data were analysed both by using organ-based volumes of interest (VOIs) to obtain the total radioactivity in the organ, and by using small VOIs to measure the tissue radioactivity concentration. During the first treatment session in 24 patients, imaging was performed 1, 24, 96 and 168 h after [{sup 177}Lu-DOTA{sup 0}, Tyr{sup 3}]octreotate infusion. Absorbed doses in non tumour-affected kidney, liver and spleen were calculated and compared for all three methods (planar imaging, SPECT organ VOIs, SPECT small VOIs). Planar and SPECT dosimetry were comparable in areas free of tumours, but due to overlap the planar dosimetry highly overestimated the absorbed dose in organs with tumours. Furthermore, SPECT dosimetry based on small VOIs proved to be more reliable than whole-organ dosimetry. We conclude that SPECT dosimetry based on small VOIs is feasible and more accurate than conventional planar dosimetry, and thus may contribute towards optimising targeted radionuclide therapy. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Caldeira Filho, Jose de Souza

    2009-07-01

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

  19. 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)

  20. No-carrier-added (NCA) N-(3-( sup 18 F)fluoropropyl)-N-norbuprenorphine and N-(3-( sup 18 F)fluoropropyl)-N-nordiprenorphine -synthesis, anatomical distribution in mice and rats, and tomographic studies in a baboon

    Energy Technology Data Exchange (ETDEWEB)

    Lanqin Bai; Renrui Teng; Chyngyann Shiue; Wolf, A.P.; Dewey, S.L. (Brookhaven National Lab., Upton, NY (USA)); Holland, M.J.; Simon, E.J. (New York Univ., NY (USA). Medical Center)

    1990-01-01

    N-(3-Fluoropropyl)-N-norbuprenorphine (3a) and N-(3-fluoropropyl)-N-nordiprenorphine (4a) were synthesized by N-alkylation of norbuprenorphine (1) and nordiprenorphine (2) with 1-bromo-3-fluoropropane. The corresponding no-carrier-added (NCA) N-(3-({sup 18}F)fluoropropyl)-N-norbuprenorphine (3b) and N-(3-({sup 18}F)fluoropropyl)-N-nordiprenorphine (4b) were synthesized by N-alkylation of 1 and 2 with NCA 1-({sup 18}F)fluoro-3-iodopropane. In vitro studies indicate that in the absence of sodium chloride, compounds 3a, 4a, N-propyl-N-norbuprenorphine (5), buprenorphine and diprenorphine are reasonably comparable in binding affinity for opioid receptors. In the presence of 100 mM sodium chloride, however, compounds 3a, 4a and 5, are clearly less potent than buprenorphine and diprenorphine. The anatomical distribution study of compound 3b in mice shows radioactivity accumulating in bone. Rat studies of both compounds 3b and 4b indicate the specific distribution of these two radioligands within certain cortical and subcortical regions of rat brain. However, the absolute uptake of compound 4b in rat brain was only half that of compound 3b. PET studies of 3b in a baboon revealed specific binding of compound 3b in striatum and cerebellum. At 1 h after injection, ratios of specific/non-specific binding of 3b in striatum and cerebellum of a baboon were 1.9 and 1.7 respectively. (author).

  1. Automated production at the curie level of no-carrier-added 6-[(18)F]fluoro-L-dopa and 2-[(18)F]fluoro-L-tyrosine on a FASTlab synthesizer.

    Science.gov (United States)

    Lemaire, C; Libert, L; Franci, X; Genon, J-L; Kuci, S; Giacomelli, F; Luxen, A

    2015-06-15

    An efficient, fully automated, enantioselective multi-step synthesis of no-carrier-added (nca) 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) and 2-[(18)F]fluoro-L-tyrosine ([(18)F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high- performance liquid chromatography (HPLC) purification has been developed. A PTC (phase-transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand-alone HPLC. [(18)F]FDOPA and [(18)F]FTYR were produced in 36.3 ± 3.0% (n = 8) and 50.5 ± 2.7% (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95%, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [(18)F]FDOPA and [(18)F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment.

  2. {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Sahoo, Ranjit Kumar [All India Institute of Medical Sciences, Department of Medical Oncology, BR Ambedkar Rotary Cancer Hospital, New Delhi (India); Seth, Amlesh [All India Institute of Medical Sciences, Department of Urology, New Delhi (India)

    2017-01-15

    The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic{sup 68}Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly {sup 177}Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity

  3. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Michael Bzorek

    2013-10-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.

  4. Efficiency of the metabolic radiotherapy with {sup 177}Lu Octreotate in the case of gastric endocrine tumor with hepatic metastases; Efficacite de la radiotherapie metabolique au{sup 177}Lu Octreotate dans le cas d'une tumeur endocrine gastrique avec metastases hepatiques

    Energy Technology Data Exchange (ETDEWEB)

    Leghzali Moise, H.; Besse, H.; Stievenart, J.L [Medecine nucleaire, hopital Beaujon, AP-HP, (France); Scigliano, S. [service hospitalier Frederic-Joliot, Orsay, (France); Mortazavi Jehannod, N.; Lebtahid, R.; Le Guludec, D. [medecine nucleaire, hopital Bichat, AP-HP, (France); Ruszniewski, P. [pancreato-gastroenterologie, hopital Beaujon, AP-HP, (France)

    2009-05-15

    The therapy means of evolved, metastases or inoperable forms of digestive endocrine tumors are limited. we illustrate a case of treatment efficiency by {sup 177}Lu-Octreotate of a well differentiated gastric endocrine tumor with hepatic metastases. conclusions: the metabolic radiotherapy of endocrine tumors constitute a new alternative of conventional treatments, showing the achievement of objective tumor responses at advanced stages, and in failure of conventional treatments. it is necessary to identify the predictive factors of the therapy response in order to optimize the results and to limit the toxicity. (N.C.)

  5. Evaluation of the cell death mechanisms activated by the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy; Evaluacion de los mecanismos de muerte celular activados por el radiofarmaco {sup 177}Lu-DOTA-anti-CD20 en un intervalo de dosis de 1 a 5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G., E-mail: erica.azorin@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2016-10-15

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation

  6. In vitro and in vivo studies in Balb-c and nude mice of a new {sup 177}Lu-Bombesin analog developed for prostate tumor diagnosis and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Pujatti, Priscilla B.; Santos, Josefina S.; Couto, Renata M.; Araujo, Elaine B. de; Mengatti, Jair [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia], e-mail: priscillapujatti@yahoo.com.br; Suzuki, Miriam F. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia

    2009-07-01

    In this work we describe the radiolabeling with {sup 177}Lu and some properties of the novel bombesin analog BBNp6 - DOTA-X-BBN(6-14), where X is a spacer of six aminoacids. Bombesin (BBN) is an analog of human gastrin releasing peptide (GRP) isolated from the skin of the frog Bombina bombina in 1970. Development of radiolabeled BBN derivatives as agents for diagnostic imaging and systemic radiotherapy has increased considerable because of the observation that GRP receptors (GRPr) are over-expressed in a variety of human tumor cells, such as prostate tumor cells. {sup 177}Lu-labeled peptides are attractive due to the excellent radiophysical properties and commercial availability of the radiometal. BBNp6 was labeled with high yield after reacting with 92.5 MBq of {sup 177}LuCl3 at 90 deg C for 30 minutes and this mixture kept stable for more than 96 hours at 4 deg C and 1 hour in human plasma. In vivo studies showed a multicompartimental distribution model with fast blood clearance, mainly performed by renal pathway. In addition, {sup 177}Lu-BBNp6 showed high affinity for PC-3 tumor xenografts, but not for pancreas and intestine (GRP positive tissues), suggesting its specificity and usefulness for prostate tumor treatment. Moreover, scintigraphic images showed that this derivative can also be a tool in this tumor diagnosis. So, BBNp6 is a promising radiopharmaceutical for prostate tumor imaging and treatment. (author)

  7. Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2015-07-15

    Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with {sup 177}Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with {sup 177}Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were

  8. Bone marrow dosimetry in peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Krenning, Eric P.; Kooij, Peter P.; Bernard, Bert F.; Bakker, Willem H.; Teunissen, Jaap J.M.; Jong, Marion de; Kwekkeboom, Dik J. [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Konijnenberg, Mark [Mallinckrodt Medical BV, Research and Development, Petten (Netherlands); Lom, Kirsten van [Erasmus MC Rotterdam, Department of Haematology, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus MC Rotterdam, Department of Internal Medicine, Rotterdam (Netherlands)

    2009-07-15

    Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called ''remainder of the body'' to the bone marrow. Bone marrow aspirates were drawn in 15 patients after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose. (1) After PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone

  9. 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

  10. (44)Sc-PSMA-617 for radiotheragnostics in tandem with (177)Lu-PSMA-617-preclinical investigations in comparison with (68)Ga-PSMA-11 and (68)Ga-PSMA-617.

    Science.gov (United States)

    Umbricht, Christoph A; Benešová, Martina; Schmid, Raffaella M; Türler, Andreas; Schibli, Roger; van der Meulen, Nicholas P; Müller, Cristina

    2017-12-01

    The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging ((68)Ga) and radionuclide therapy ((177)Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced (44)Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to (177)Lu-PSMA-617. (44)Sc was produced at the research cyclotron at PSI by irradiation of enriched (44)Ca targets, followed by chromatographic separation. (44)Sc-PSMA-617 was prepared under standard labeling conditions at elevated temperature resulting in a radiochemical purity of >97% at a specific activity of up to 10 MBq/nmol. (44)Sc-PSMA-617 was evaluated in vitro and compared to the (177)Lu- and (68)Ga-labeled match, as well as (68)Ga-PSMA-11 using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu prostate cancer cells. In these experiments it revealed similar in vitro properties to that of (177)Lu- and (68)Ga-labeled PSMA-617. Moreover, (44)Sc-PSMA-617 bound specifically to PSMA-expressing PC-3 PIP tumor cells, while unspecific binding to PC-3 flu cells was not observed. The radioligands were investigated with regard to their in vivo properties in PC-3 PIP/flu tumor-bearing mice. (44)Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of (44)Sc-PSMA-617 resembled that of (177)Lu-PSMA-617 most closely, while the (68)Ga-labeled ligands, in particular (68)Ga-PSMA-11, showed different distribution kinetics. (44)Sc-PSMA-617 enabled distinct visualization of PC-3 PIP tumor xenografts shortly after injection, with increasing tumor-to-background contrast over time while unspecific uptake in the PC-3 flu tumors was not observed. The in vitro

  11. Occupational doses in neuroendocrine tumors by using {sup 177}Lu DOTATATE; Doses ocupacionais em tratamento de tumores neuroendocrinos utilizando {sup 17'}7Lu DOTATATE

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Gustavo Coelho Alves; Sa, Lidia Vasconcellos de, E-mail: gustavo@ird.gov.b, E-mail: lidia@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-10-26

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of {sup 177}Lu DOTATATE radiopharmaceutical which is a type of treatment presently used in the experimental form in Brazil and, therefore, not contemplated in norms or specific use. This research studied the occupational doses of this treatment and suggested guidelines or rules of procedures viewing the radiological protection of workers involved and the public. The treatment were followed up by using two types of radiation detection, one a scintillator and a Geiger-Muller, and the measurements were performed in a public hospital at Rio de Janeiro and the other in a private hospital at Sao Paulo. It was observed that the equivalent occupational doses can variate from 160 {mu}Sv to 450 {mu}Sv, in function of operator, of stage of manipulation, and of the administration method, which can be through the use of infusion pump or manual injection. The use of infusion pump is highly recommended and the hospitalization of the patient until the dose rate measured at 1 m does not surpass 20 {mu}Sv/h

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

    Directory of Open Access Journals (Sweden)

    Mohammad Mirzaei

    2015-04-01

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

  13. 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)

  14. First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease.

    Science.gov (United States)

    Herrmann, Ken; Schottelius, Margret; Lapa, Constantin; Osl, Theresa; Poschenrieder, Andreas; Hänscheid, Heribert; Lückerath, Katharina; Schreder, Martin; Bluemel, Christina; Knott, Markus; Keller, Ulrich; Schirbel, Andreas; Samnick, Samuel; Lassmann, Michael; Kropf, Saskia; Buck, Andreas K; Einsele, Hermann; Wester, Hans-Juergen; Knop, Stefan

    2016-02-01

    Chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. Based on promising experiences with a radiolabeled CXCR4 ligand ((68)Ga-pentixafor) for diagnostic receptor targeting, (177)Lu- and (90)Y-pentixather were recently developed as endoradiotherapeutic vectors. Here, we summarize the first-in-human experience in 3 heavily pretreated patients with intramedullary and extensive extramedullary manifestations of multiple myeloma undergoing CXCR4-directed endoradiotherapy. CXCR4 target expression was demonstrated by baseline (68)Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic (177)Lu-pentixather dosimetry was performed before (177)Lu-pentixather or (90)Y-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in (18)F-FDG uptake. CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stem cell transplantation, especially for patients with advanced multiple myeloma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  15. Formulation and evaluation of freeze-dried DOTMP kit for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP at the hospital radiopharmacy

    Energy Technology Data Exchange (ETDEWEB)

    Das, Tapas; Banerjee, Sharmila [Bhabha Atomic Research Centre, Radiopharmaceuticals Chemistry Section, Mumbai (India); Chakraborty, Sudipta [Bhabha Atomic Research Centre, Isotope Production and Applications Div., Mumbai (India); Sarma, Haladhar D. [Bhabha Atomic Research Centre, Radiation Biology and Health Sciences Div., Mumbai (India)

    2015-07-01

    The objective of the present work is to develop and evaluate freeze-dried DOTMP kit, which could be utilized for the convenient and single-step preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP, both of which have shown potential as alternative agents for metastatic bone pain palliation. Freeze-dried DOTMP kits, each comprising a lyophilized mixture of 20 mg DOTMP and 8.75 mg NaOH, were prepared. The kits were used for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP complexes. The agents were prepared by dissolving the lyophilized powder in 1 mL of normal saline and incubating with {sup 177}LuCl{sub 3} or {sup 153}SmCl{sub 3}, produced in-house, for 15 min at room temperature. Pharmacokinetic behavior and biological distribution of the agents were studied by carrying out biodistribution as well as scintigraphic studies in normal male Wistar rats. Shelf-life of the freeze-dried kits was also ascertained. Clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP complexes, comprising up to 3.7 GBq (100 mCi) of activity, were prepared with > 99% radiochemical purity using the freeze-dried kits. The complexes exhibited high in vitro stability when stored at room temperature. Biological studies showed selective skeletal accumulation and insignificant uptake of the radiotracers in any of the vital organs/tissue. The non-accumulated activity exhibited primary urinary clearance. The kits had a shelf-life of 2 years when stored at 4 C temperature. Freeze-dried DOTMP kits, suitable for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP, have been developed and the radiochemical and biological behaviors of the radiolabeled agents have been studied. The use of the kit at the hospital radiopharmacy is expected to make the preparations easy and convenient. This in turn will enable the widespread dissemination of these promising agents towards their application for regular use.

  16. The {sup 68}Ga/{sup 177}Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUV{sub max} values and absorbed dose estimates

    Energy Technology Data Exchange (ETDEWEB)

    Scarpa, Lorenza; Buxbaum, Sabine; Kendler, Dorota; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Fink, Katharina [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Medical University of Innsbruck, Department of Radiotherapy / Radiation Oncology, Innsbruck (Austria); Bektic, Jasmin; Horninger, Wolfgang [Medical University of Innsbruck, Department of Urology, Innsbruck (Austria); Gruber, Leonhard [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Lukas, Peter [Medical University of Innsbruck, Department of Radiotherapy / Radiation Oncology, Innsbruck (Austria)

    2017-05-15

    A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Ten consecutive mCRPC patients were selected for {sup 177}Lu-PSMA617 therapy on the basis of PSMA-targeted {sup 68}Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging ({sup 68}Ga-PSMA-HBED-CC and {sup 18}F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to {sup 177}Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. {sup 177}Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased {sup 177}Lu-PSMA617 and {sup 68}Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following {sup 177}Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study. (orig.)

  17. Outcome of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Ezziddin, Samer; Khalaf, Feras; Vanezi, Maria; Haslerud, Torjan; Zreiqat, Abdullah Al; Biersack, Hans-Juergen; Sabet, Amir [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Willinek, Winfried [University Hospital, Department of Radiology, Bonn (Germany)

    2014-05-15

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with {sup 177}Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with {sup 177}Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial {sup 99m}Tc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis

  18. Feasibility and utility of re-treatment with {sup 177}Lu-DOTATATE in GEP-NENs relapsed after treatment with {sup 90}Y-DOTATOC

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola, FC (Italy); Bodei, Lisa [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Ibrahim, Toni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); D' Errico, Vincenzo [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2015-12-15

    Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 - 3 years. In the present study, we investigated the use of low dosage re-treatment with {sup 177}Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with {sup 90}Y-DOTATOC (Y-PRRT). Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 - 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated. Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6 %, median PFS was 22 months (95 % CI 16 months - not reached) compared to 28 months (95 % CI 20 - 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity. Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment. (orig.)

  19. Synthesis and stability test of radioimmunoconjugate 177Lu-DOTA-F(ab′2-trastuzumab for theranostic agent of HER2 positive breast cancer

    Directory of Open Access Journals (Sweden)

    Sandra Hermanto

    2016-10-01

    Full Text Available The use of trastuzumab as intact IgG labeling radionuclide for HER2 positive breast cancer theranostic agent is not ideal because it is slowly eliminated from the blood and normal tissues resulting in low tumor/blood (T/B and tumor/normal tissue (T/NT ratios. To overcome this limitation, we developed the trastuzumab F(ab′2 fragments and radiolabeling of the fragments by β and γ-particle of Lutetium-177. F(ab2 fragments were produced by digestion of trastuzumab IgG (Herceptin with pepsin for 18 h at 37 °C. The F(ab′2 fragment fractionated in PD-10 column, followed by the conjugation with 2-(4-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA as a metal chelator and radiolabeling with 177LuCl3. Molecular weight of fragments was calculated by LCMS (Liquid Chromatography Mass Spectroscopy and the radiochemical purity was evaluated by ITLC-SG (Instan Thin Layer Chromatography. Our study showed that the purity of F(ab′2 fragment generated by PD-10 fractions was >98% and the molecular weight of F(ab′2 was 98.35 kDa. The average numbers of pSCN-Bn-DOTA chelates per antibody fragment were 5.03 ± 1.5 and the optimum conjugation reactions was performed at molar ratio 20:1 (chelator to antibody. The stability test of the radioimmunoconjugate in the human serum albumin (HSA at 37 °C showed the radiochemical purity was 91.96 ± 0.26% after 96 h storage. This indicated that the radioimmunoconjugate is relatively stable when applied to the human body's physiological condition.

  20. Influence of biological assay conditions on stability assessment of radiometal-labelled peptides exemplified using a {sup 177}Lu-DOTA-minigastrin derivative

    Energy Technology Data Exchange (ETDEWEB)

    Ocak, Meltem [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Helbok, Anna; Guggenberg, Elisabeth von [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Ozsoy, Y. [Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Kabasakal, Levent [Department of Nuclear Medicine, Cerrahpasa Medical Faculty, 34098, Istanbul (Turkey); Kremser, Leopold [Division of Clinical Biochemistry, Protein Micro-Analysis Facility, Biocenter, Medical University Innsbruck, A-6020, Innsbruck (Austria); Decristoforo, Clemens, E-mail: clemens.decristoforo@uki.a [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria)

    2011-02-15

    Introduction: Lack of correlation between in vitro and in vivo stability is a general problem for the development of radiopeptides especially in the case of minigastrin derivatives for therapeutic applications. In this study, we compared the influence of experimental conditions on radiopeptide stability results in vitro using a model Minigastrin (MG) analogue labelled with Lu-177. Additionally, we attempted to characterize the main serum enzymatic cleavage sites by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) analysis. Methods: In vitro stability of a DOTA-minigastrin derivative ({sup 177}Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-NIe-Asp-Phe-NH{sub 2}) was tested in serum, rat tissue homogenates and two different standardised enzymatic mixtures. Quantification of the metabolised radiopeptides at different time intervals was performed using reversed-phase high-performance liquid chromatography (RP-HPLC). Metabolites were characterised by MALDI-TOF-MS. Urine was collected after 15 min p.i. into the mice and compared with in vitro metabolites by RP-HPLC. Results: Faster degradation of the radiopeptide was found in blood in comparison with plasma and serum incubation and in components from rats faster than from human origin. Fast degradation was observed in kidney and liver homogenates as well as in standardised enzymatic mixtures, also revealing variations in the metabolic profile. In urine, no intact peptide was detected already 5 min post injection. MALDI-TOF-MS revealed major cleavage sites at the carboxy terminus of the peptide. Conclusion: Very variable results may be found when different kind of incubation media for testing radiopeptide stabilities is used. Serum incubation studies may overestimate stability; therefore, results should be interpreted with care and combined with alternative in vitro and in vivo investigations.

  1. Rapid blood clearance and lack of long-term renal toxicity of {sup 177}Lu-DOTATATE enables shortening of renoprotective amino acid infusion

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Jackson, Price [Peter MacCallum Cancer Centre, Department of Physical Sciences, Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); The University of Melbourne, Departments of Medicine and Radiology, Melbourne (Australia); Beauregard, Jean-Mathieu [Universite Laval, Department of Radiology, Quebec City (Canada); Zannino, Diana [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne (Australia)

    2013-12-15

    The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of {sup 177}Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation. (orig.)

  2. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Ianniello, Annarita; Sansovini, Maddalena; Severi, Stefano; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Unit, Meldola (Italy); Grana, Chiara Maria [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy); Massri, Katrin [Ospedale San Luca, Nuclear Medicine, Department of Radiology, Lucca (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Antonuzzo, Lorenzo [AOU Careggi, SC Oncologia Medica 1, Firenze (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela; Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2016-06-15

    Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and {sup 18}F-FDG PET as prognostic factors in patients with advanced TC or AC. A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients. The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group. Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of

  3. Role of {sup 18}FDG PET/CT in patients treated with {sup 177}Lu-DOTATATE for advanced differentiated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Matteucci, Federica [Cancer Institute of Romagna (IRST), Unit of Radiometabolic Medicine, Meldola, FC (Italy); Nanni, Oriana; Scarpi, Emanuela [Cancer Institute of Romagna (IRST), Unit of Biostatistics and Clinical Trials, Meldola, FC (Italy); Bodei, Lisa; Gilardi, Laura; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Nicoletti, Stefania [Cancer Institute of Romagna (IRST), Unit of Medical Oncology, Meldola, FC (Italy)

    2013-06-15

    The prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after {sup 177}Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade 1/2 NETs. We retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7 GBq divided into five courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index {<=}2 %, 19 patients), and those with grade 2 tumour (Ki-67 index >3 % to <20 %, 33 patients). On the basis of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET-). FDG PET was positive in 57 % of patients with grade 1 NET and in 66 % of patients with grade 2 NET, and the rates of disease control (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95 % and 79 %, respectively (P = 0.232). In PET- and PET+ patients, the DC rates were 100 % and 76 % (P = 0.020) with a PFS of 32 and 20 months, respectively (P = 0.033). Of the PET+ patients with grade 1 NET, 91 % showed disease control, whereas about one in three PET+ patients with grade 2 NET (32 %) progressed after Lu-PRRT (DC rate 68 %). These results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients with grade 1/2 advanced NETs. Notably, none of PET- patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32 % of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT. (orig.)

  4. Peptide receptor radionuclide therapy with {sup 90}Y/{sup 177}Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours)

    Energy Technology Data Exchange (ETDEWEB)

    Puranik, Ameya D.; Kulkarni, Harshad R.; Singh, Aviral; Baum, Richard P. [Zentralklinik Bad Berka, THERANOSTICS Centre for Molecular Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka (Germany)

    2015-07-15

    Head and neck paragangliomas (HNPGLs) are rare tumours arising from autonomic nervous system ganglia. Although surgery offers the best chance of complete cure, there is associated morbidity due to the crucial location of these tumours. Radiotherapy arrests tumour growth and provides symptomatic improvement, but has long-term consequences. These tumours express somatostatin receptors (SSTR) and hence peptide receptor radionuclide therapy (PRRT) is now a treatment option. We assessed the molecular, morphological and clinical responses of inoperable HNPGLs to PRRT. Nine patients with inoperable HNPGL assessed between June 2006 and June 2014 were included. Four patients had a solitary lesion, four had multifocal involvement and one had distant metastases (bone and lungs). The patients were treated with PRRT using {sup 90}Y/{sup 177}Lu-labelled peptides after positive confirmation of SSTR expression on {sup 68}Ga-DOTATOC PET/CT. All patients received two to four courses of PRRT. Subsequent serial imaging with {sup 68}Ga-DOTATOC PET/CT was carried out every 6 months to assess response to treatment. Clinical (symptomatic) response was also assessed. Based on molecular response (EORTC) criteria, four of the nine patients showed a partial molecular response to treatment seen as significant decreases in SUV{sub max}, accompanied by a reduction in tumour size. Five patients showed stable disease on both molecular and morphological criteria. Six out of nine patients were symptomatic at presentation with manifestations of cranial nerve involvement, bone destruction at the primary site and metastatic bone pain. Molecular responses were correlated with symptomatic improvement in four out of these six patients; while two patients showed small reductions in tumour size and SUV{sub max}. The three asymptomatic patients showed no new lesions or symptomatic worsening. PRRT was effective in all patients, with no disease worsening seen, either in the form of neurological symptoms or

  5. Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of (177)Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience.

    Science.gov (United States)

    Shinto, Ajit S; Kamaleshwaran, K K; Chakraborty, Sudipta; Vyshakh, K; Thirumalaisamy, S G; Karthik, S; Nagaprabhu, V N; Vimalnath, K V; Das, Tapas; Banerjee, Sharmila

    2015-01-01

    The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using (177)Lu-labeled hydroxyapatite ((177)Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of (177)Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of (177)Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes

  6. Pre-therapeutic dosimetry of normal organs and tissues of {sup 177}Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent; AbuQbeitah, Mohammad; Ayguen, Aslan; Yeyin, Nami [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Demirci, Emre [Sisli Etfal Training and Research Hospital, Department of Nuclear Medicine, Istanbul (Turkey); Toklu, Turkay [Yeditepe University Medical Faculty, Department of Nuclear Medicine, Istanbul (Turkey)

    2015-12-15

    {sup 177}Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of {sup 177}Lu-labeled PSMA ligand. The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected {sup 177}Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Our first results suggested that {sup 177}Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are

  7. In vitro and in vivo evaluation of {sup 177}Lu- and {sup 9}Y-labeled E. coli heat-stable enterotoxin for specific targeting of uroguanylin receptors on human colon cancers

    Energy Technology Data Exchange (ETDEWEB)

    Giblin, Michael F. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States) and Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)]. E-mail: giblinm@health.missouri.edu; Sieckman, Gary L. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Shelton, Tiffani D. [Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Hoffman, Timothy J. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Forte, Leonard R. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Medical Pharmacology and Physiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Volkert, Wynn A. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)

    2006-05-15

    The human E. coli heat-stable enterotoxin (ST{sub h}, amino acid sequence N{sup 1}SSNYCCELCCNPACTGCY{sup 19}) binds specifically to the guanylate cyclase C (GC-C) receptor, which is present in high density on the apical surface of normal intestinal epithelial cells as well as on the surface of human colon cancer cells. Analogs of ST{sub h} are currently being used as vectors targeting human colon cancers. Previous studies in our laboratory have focused on development of {sup 111}Indium-labeled ST{sub h} analogs for in vivo imaging applications. Here, we extend the scope of this work to include targeting of the therapeutic radionuclides {sup 9}Y and {sup 177}Lu. The peptide DOTA-F{sup 19}-ST{sub h}(1-19) was synthesized using conventional Fmoc-based solid-phase techniques and refolded in dilute aqueous solution. The peptide was purified by RP-HPLC and characterized by MALDI-TOF MS and in vitro receptor binding assay. The DOTA-conjugate was metallated with nonradioactive Lu(III)Cl{sub 3} and Y(III)Cl{sub 3}, and IC{sub 5} values of 2.6{+-}0.1 and 4.2{+-}0.9 nM were determined for the Lu- and Y-labeled peptides, respectively. {sup 177}Lu(III)Cl{sub 3} and {sup 9}Y(III)Cl{sub 3} labeling yielded tracer preparations that were inseparable by C18 RP-HPLC, indicating that putative differences between Lu-, Y- and In coordination spheres are not observed in the context of labeled ST{sub h} peptides. In vivo biodistribution studies of the {sup 177}Lu-labeled peptide in severe combined immunodeficient (SCID) mice bearing T-84 human cancer tumor xenografts showed rapid clearance from the bloodstream, with >90 %ID in the urine at 1 h pi. Localization of the tracer within tumor xenografts was 1.86{+-}0.91 %ID/g at 1 h pi, a value higher than for all other tissues with the exception of kidney (2.74{+-}0.24 %ID/g). At 24 h pi, >98 %ID was excreted into the urine, and 0.35{+-}0.23 %ID/g remained in tumor, again higher than in all other tissues except kidney (0.91{+-}0.46 %ID

  8. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity {sup 86}Y- or {sup 177}Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Xu, Hong; Guo, Hong-fen [Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Chalasani, Sandhya; Carrasquillo, Jorge A. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Fung, Edward K. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Jungbluth, Achim [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Zanzonico, Pat B.; O' Donoghue, Joseph [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Smith-Jones, Peter M. [Stony Brook University, Department of Psychiatry and Behavioral Science, Stony Brook, NY (United States); Stony Brook University, Department of Radiology, Stony Brook, NY (United States); Wittrup, K.D. [Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Cambridge, MA (United States); Cheung, Nai-Kong V. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States)

    2016-05-15

    GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens {sup 177}Lu-or {sup 86}Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq {sup 177}Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm{sup 3}) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm{sup 3} tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten {sup 86}Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

  9. Monte Carlo Calculation of Radioimmunotherapy with (90)Y-, (177)Lu-, (131)I-, (124)I-, and (188)Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts.

    Science.gov (United States)

    Lucas, S; Feron, O; Gallez, B; Masereel, B; Michiels, C; Vander Borght, T

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  10. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    Directory of Open Access Journals (Sweden)

    S. Lucas

    2015-01-01

    Full Text Available Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP and normal tissue complication probability (NTCP curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC. 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  11. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    Science.gov (United States)

    Lucas, S.; Feron, O.; Gallez, B.; Masereel, B.; Michiels, C.; Vander Borght, T.

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases. PMID:26136812

  12. Out sourcing treatments by {sup 177}Lu-Dotatoc of multi metastatic digestive neuroendocrine tumors: experience of a endocrine tumor pluri-disciplinary consultation meeting; Externalisation des traitements par Lu177-Dotatoc des tumeurs neuro-endocrines digestives multimetastatiques: l'experience d'une RCP de tumeurs endocrines

    Energy Technology Data Exchange (ETDEWEB)

    Dierickx, L.O.; Zerdoud, S.; Brillouet, S.; Courbon, F. [Institut Claudius-Regaud (CLCC), 31 - Toulouse (France); Duffas, J.P.; Danjoux, M.; Buscail, L.; Otal, P.; Guimbaud, R. [CHU Rangueil, 31 - Toulouse (France); Caron, P. [CHU Larrey, 49 - Angers (France)

    2010-07-01

    {sup 177}lu-Dotatoc could be a significant progress for internal vectorized radiotherapy of metastatic endocrine tumors. This therapy modality is currently only available abroad. Since 2006, we give indication for some patients of ours we address in these foreign centers. The treatment organisation, the management abroad, and the reimbursement as well as the the responses and the toxicity of the treatment have been evaluated. Conclusions: The results of the treatments are consistent with literature. The externalization of the treatment is feasible, well accepted but heavy to hold. In addition, to our knowledge, on 7 centers in Europe, the costs of care ranged from 3000 to 12000 Euros / injection. (N.C.)

  13. Study by Monte Carlo simulation of the absorbed dose in cells of breast cancer of the line MDA-MB231, due to sources of {sup 111}In, {sup 177}Lu and {sup 99m}Tc internalized in the nucleus. First results; Estudio por simulacion Monte Carlo de la dosis absorbida en celulas de cancer de seno de la linea MDA-MB231, debida a fuentes de {sup 11I}n, {sup 177}Lu y {sup 99m}Tc internalizadas en el nucleo. Primeros resultados

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E. L.; Perez A, M., E-mail: leticia.rojas@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2011-11-15

    The necessity to design innovative treatments and to diagnose the cancer early, has taken to investigate therapies at cellular and molecular level. The design of appropriate radio-molecules to these therapies makes necessary to characterize in way exhaustive radionuclides that they are of accessible production in our country and to study as distributing the dose at cellular level with bio-molecules glued them. In this context, was realized the present work. Using Monte Carlo simulation, the energy deposited in a geometric model of cells of breast cancer was obtained, MDA-MB231, due to different radionuclides. The energy deposited in the nucleus was evaluated, in the cytoplasm and in the membrane of the cell, using the simulation code Monte Carlo Penelope 2008. A punctual source was simulated in the center of the cell nucleus. In each case all the emissions of each radionuclide majors to 400 eV were simulated. The energies deposited by disintegration in the nucleus, cytoplasm, membrane of the cell and in a sphere of 2 cm surrounding the source (in eV) were: 4.30E3, 4.85E2, 1.07E2 and 3.29E4, correspondingly, for the {sup 111}In; 4.46E3, 3.76E3, 1.26E3 and 1.33E5 for the {sup 177}Lu and; 2.12E3, 2.58E2, 9.33E1 and 1.88E4 for the {sup 99m}Tc. We can conclude that if the union of these radionuclides happens to a compound that was internalized to the cell nucleus, the best for therapy at this level is the conjugate with the {sup 177}Lu, followed by that with {sup 111}In and in third place that with {sup 99m}Tc. (Author)

  14. The use of 99mTc-HYNIC-TOC and 18F-FDG PET/CT in the evaluation of duodenal neuroendocrine tumor with atypical and extensive metastasis responding dramatically to a single fraction of PRRT with 177Lu-DOTATATE.

    Science.gov (United States)

    Basu, Sandip; Abhyankar, Amit

    2014-12-01

    This report describes a case of extensive diffuse bone marrow involvement with bilateral breast metastases from duodenal neuroendocrine tumor giving rise to a superscan-like appearance on somatostatin receptor-targeted (99m)Tc-hydrazinonicotinamide-TOC scintigraphy. The metastatic lesions demonstrated partial concordance with (18)F-FDG PET/CT findings, signifying varying tumor biology and heterogeneity among metastatic lesions in the same individual, as illustrated with a dual-tracer approach. There was a dramatic symptomatic and biochemical response and better health-related quality of life with a single fraction of peptide receptor radionuclide therapy with (177)Lu-DOTATATE, and radiologically there was stable disease at that point.

  15. Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders [Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden)

    2012-07-15

    Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom

  16. Optimized separation procedure for production of no-carrier-added radiomanganese for positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, Martin; Spahn, Ingo; Coenen, Heinz H. [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Neurowissenschaften und Medizin (INM), Nuklearchemie (INM-5)

    2015-07-01

    The {sup nat}Cr(p,xn)-process is a very efficient route for production of {sup 52g}Mn(T{sub 1/2} = 5.59 d). Based on measurements of distribution coefficients with different media and ion-exchange resins, an optimized chromatographic separation of radiomanganese from {sup nat}Cr with the resin Amberlite CG400 was developed. With this system {sup nat}Cr is eluted first with an acetic acid/methanol 1:1 mixture at room temperature and {sup 52g}Mn thereafter with 3 M HCl at 50 C. Within a separation time of 4 h the method yielded 99.5% of the n.c.a. {sup 52g}Mn in 2-3 mL of 3 M HCl. An ICP-MS analysis revealed a chromium impurity of 0.07 mg (0.014%) in the n.c.a. {sup 52g}Mn solution, making this separation method suitable for the production of {sup 52g}Mn for medical applications like positron emission tomography (PET).

  17. Study on No- carrier-added Separation of 126Sn From High-level Liquid Waste

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    126Sn is a long-lived fission product nuclide, its fission yield values, in fission of 235U by thermalneutron, fission spectrum neutron and high energy neutron, are 5.59×10-2%, 1.39×10-1% and 1.76%,respectively. So scientists are paying more attention to 126Sn in high radioactive waste disposal.

  18. Direct flow separation strategy, to isolate no-carrier-added {sup 90}Nb from irradiated Mo or Zr targets

    Energy Technology Data Exchange (ETDEWEB)

    Radchenko, Valery; Roesch, Frank [Mainz Univ. (Germany). Inst. of Nuclear Chemistry; Filosofov, Dmitry V.; Dadakhanov, Jakhongir [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Karaivanov, Dimitar V. [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Bulgarian Academy of Sciences, Sofia (Bulgaria). Inst. for Nuclear Research and Nuclear Energy; Marinova, Atanaska [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Sofia Univ. (Bulgaria). Faculty of Chemistry and Pharmacy; Baimukhanova, Ayagoz [Joint Institute of Nuclear Research, Dubna (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Institute of Nuclear Physics of the Republic of Kazakhstan, Almaty (Kazakhstan)

    2016-11-01

    {sup 90}Nb has an intermediate half-life of 14.6 h, a high positron branching of 53% and optimal β{sup +} emission energy of only E{sub mean} 0.35 MeV per decay. These favorable characteristics suggest it may be a potential candidate for application in immuno-PET. Our recent aim was to conduct studies on distribution coefficients for Zr{sup IV} and Nb{sup V} in mixtures of HCl/H{sub 2}O{sub 2} and HCl/oxalic acid for anion exchange resin (AG 1 x 8) and UTEVA resin to develop a ''direct flow'' separation strategy for {sup 90}Nb. The direct flow concept refers to a separation accomplished using a single eluent on multiple columns, effectively streamlining the separation process and increasing the time efficiency. Finally, we also demonstrated that this separation strategy is applicable to the production of the positron emitter {sup 90}Nb via the irradiation of molybdenum targets and isolation of {sup 90}Nb from the irradiated molybdenum target.

  19. Separation of no-carrier-added Cu-64 from a proton irradiated Ni-64 enriched nickel target

    DEFF Research Database (Denmark)

    Hou, Xiaolin; Jacobsen, U.; Jørgensen, J.C.

    2002-01-01

    are then absorbed on an anion exchange column. Co and Ni are removed from the column by eluting with 72% ethanol-0.3mol/l HCl. Finally, the Cu-64 is eluted with water. For separating Ni from Co isotopes and recovering the Ni-64 target, the eluate of 72% ethanol-0.3 mol/l HCl is evaporated to dryness, the residue...... a cyclotron. The decontamination of Co in Cu fraction is higher than 99% and recoveries of Cu-64 and Ni-64 are higher than 95%. (C) 2002 Elsevier Science Ltd. All rights reserved....

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

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2015-07-01

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

  1. Preparation and 177Lu Labeling of p-SCN-Bn-DOTA-h-R3

    Institute of Scientific and Technical Information of China (English)

    DENG; Xin-rong; FAN; Cai-yun; LUO; Zhi-fu

    2013-01-01

    The humanized monoclonal antibodies(mAbs)h-R3 has been used as a targeting biomolecule better than other anti-EGFR(epidermal growth factor receptor)for the delivery of radionuclide onto tumor cells in radio immunotherapy(RIT).Several bifunctional chelating agents(BCAs)could be used as a bridge coupling h-R3 and radiometals.In this study,h-R3 was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,

  2. Preparation, Radiolabelling and Biodistribution Study of ~(177)Lu-DTPA-G3

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Polyamidoamine (PAMAM) dendrimers are new artificial macromolecules with tree-like structure and have characteristics of greater water-solubility, bioavailability and compatibility. It can be carried by the drug molecules. PAMAM have been

  3. Production of {sup 177}Lu, a potential radionuclide for diagnostic and therapeutic applications

    Energy Technology Data Exchange (ETDEWEB)

    Khandaker, Mayeen Uddin; Kassim, Hasan Abu [Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Haba, Hiromitsu [Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan)

    2015-04-24

    {sup 177g}Lu (T{sub 1/2}=6.647d; E{sub β{sup −max}}=498.3KeV, I{sub β{sup −total}}=100%; E{sub γ} = 112.9498 keV, I{sub γ} = 6.17%; E{sub γ} = 208.3662 keV, I {sub γ} = 10.36%) is widely used in many clinical procedures due to its excellent decay characteristics. Production cross-sections of the {sup nat}Yb(d,x){sup 177g}Lu reactions have been measured from a 24-MeV deuteron energy down to the threshold by using a stacked-foil activation technique combined with high resolution γ-ray spectrometry. An overall good agreement is found with some of the earlier measurements, whereas a partial agreement is obtained with the theoretical data extracted from the TENDL-2013 library. Physical thick target yield for the {sup 177g}Lu radionuclide was deduced using the measured cross-sections. The deduced yield curves indicate that a low energy (<11 MeV) cyclotron and a highly enriched {sup 176}Yb target could be used to obtain {sup 177g}Lu with negligible impurity from {sup 177m}Lu.

  4. Skin dose saving of the staff in 90Y/177Lu peptide receptor radionuclide therapy with the automatic dose dispenser.

    Science.gov (United States)

    Fioroni, Federica; Grassi, Elisa; Giorgia, Cavatorta; Sara, Rubagotti; Piccagli, Vando; Filice, Angelina; Mostacci, Domiziano; Versari, Annibale; Iori, Mauro

    2016-10-01

    When handling Y-labelled and Lu-labelled radiopharmaceuticals, skin exposure is mainly due to β-particles. This study aimed to investigate the equivalent dose saving of the staff when changing from an essentially manual radiolabelling procedure to an automatic dose dispenser (ADD). The chemist and physician were asked to wear thermoluminescence dosimeters on their fingertips to evaluate the quantity of Hp(0.07) on the skin. Data collected were divided into two groups: before introducing ADD (no ADD) and after introducing ADD. For the chemist, the mean values (95th percentile) of Hp(0.07) for no ADD and ADD are 0.030 (0.099) and 0.019 (0.076) mSv/GBq, respectively, for Y, and 0.022 (0.037) and 0.007 (0.023) mSv/GBq, respectively, for Lu. The reduction for ADD was significant (t-test with Pisotopes. The relative differences before and after ADD collected for every finger were treated using the Wilcoxon test, proving a significantly higher reduction in extremity dose to each fingertip for Lu than for Y (Pmedical staff, the mean values of Hp(0.07) (95th percentile) for no ADD and ADD are 0.021 (0.0762) and 0.0143 (0.0565) mSv/GBq, respectively, for Y, and 0.0011 (0.00196) and 0.0009 (0.00263) mSv/GBq, respectively, for Lu. The t-test provided a P-value less than 0.05 for both isotopes, making the difference between ADD and no ADD significant. ADD positively affects the dose saving of the chemist in handling both isotopes. For the medical staff not directly involved with the introduction of the ADD system, the analysis shows a learning curve of the workers over a 5-year period. Specific devices and procedures allow staff skin dose to be limited.

  5. Does the pretherapeutic tumor SUV in 68Ga DOTATOC PET predict the absorbed dose of 177Lu octreotate?

    Science.gov (United States)

    Ezziddin, Samer; Lohmar, Jonas; Yong-Hing, Charlotte J; Sabet, Amir; Ahmadzadehfar, Hojjat; Kukuk, Guido; Biersack, Hans-Jürgen; Guhlke, Stefan; Reichmann, Karl

    2012-06-01

    Selection of candidates for peptide receptor radionuclide therapy (PRRT) is increasingly based on receptor positron emission tomography (PET) imaging, including the common tracer 68Ga DOTATOC. However, no studies have yet compared standardized uptake values (SUVs) and absorbed doses in this field. We retrospectively analyzed a consecutive cohort of 21 patients with 61 evaluable tumor lesions undergoing both pretherapeutic 68Ga DOTATOC-PET/CT (Biograph Duo [Siemens Medical Solutions, Erlangen, Germany]; PET acquisition, 75.3 ± 15.4 minutes postinjection; 117.3 ± 33.9 MBq 68Ga DOTATOC) and PRRT with Lu octreotate (7.47 ± 1.39 GBq; intratherapeutic tumor dosimetry with serial whole-body scans; 1, 2, and 4 days postinjection) at our institution. SUVs were compared with the tumor-absorbed doses per injected activity (D/A0) of the subsequent first treatment cycle. The correlation of SUV and D/A0 was r = 0.72 (SUVmean) and r = 0.71 (SUVmax), both P 15; SUVmax >25) resulted in high D/A0 (>10 Gy/GBq) in 66.7% to 70.8% and low D/A0 (<5 Gy/GBq) in only 8.3% to 12.5% on subsequent PRRT. The mentioned low D/A0 range, on the other hand, was achieved by all lesions with SUVmean <7 or SUVmax <9. Somatostatin receptor PET imaging may predict tumor-absorbed doses. The ability to indicate insufficient target irradiation by a low SUV could aid in selection of appropriate candidates for PRRT. However, larger series are needed to confirm and validate these initial findings.

  6. Investigation of models with temporal and spatial interference in image based dosimetry of {sup 177}Lu-labelled radioligand therapies

    Energy Technology Data Exchange (ETDEWEB)

    Delker, Andreas

    2016-07-12

    In targeted radio ligand therapy determination of the regional distribution of the radiation dose is mandatory for the development of therapy strategies which aim for maximizing the therapeutic effect on the tumor, while reducing radiation exposure to healthy tissue. For this purpose, after administration of the therapeutic agent, sequential measurements with a scintillation camera are required to quantitatively assess the kinetics and distribution of the radiopharmaceutical in the body. To improve the accuracy and robustness of existing dosimetric concepts, the kinetic of Lu-177-DOTATATE, a radiopharmaceutical for the treatment of patients with neuroendocrine tumors, was examined in depth. Subsequently, the findings from this study were used to carry out the first image-based dosimetry for the new active substance Lu-177-PSMA, a radiopharmaceutical for the treatment of patients with metastatic prostate cancer. Due to the specific distribution pattern of this ligand, overlay effects in the 2-dimensional (2-D) planar projection were observed. Therefore a quantitative 3-dimensional (3-D) SPECT imaging technique was established and optimized for dosimetry. To characterize the dynamics of Lu-177-DOTATATE, whole-body planar projections of 105 patients were recorded at 1, 24, 48 and 72 h after injection. Furthermore, the first hour beginning with the start of the therapeutic agent administration was measured in 12 time frames with duration of 5 min each. An optimal dose model was introduced for the kidneys, for those being a risk organ in this therapy, which consisted of three phases: a linear increase of tracer accumulation during infusion, followed by a 2-phase model being described by a bi-exponential decline. This full data model served as a basis for comparison with reduced data models based on mono-exponentials which made use of all four (at 1, 24, 48 and 72 h after injection) or the last three whole-body scintigraphies. The established quantitative 3-D SPECT technique presented a sufficient recovery of known activity in medium size spherical objects with more than 30 mm diameter (approx. 80 % and above), although a significant underestimation of activity was observed in smaller spheres. With this 3-D dosimetry an estimated dose of 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq) and 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq) could be reported. The dose to the salivary glands, being assessed with 2-D dosimetry, was 5.1 ± 1.8 Gy (1.4 Gy/GBq). By combining all available 2-D- and 3-D-dosimetric data the absorbed dose of the bone marrow was estimated with 44 ± 19 mGy (0.012 Gy/GBq). Kinetic analyses of the renal uptake revealed a fast and slow washout phase. Thereby, the slow phase component was found to be responsible to cause the major fraction of the absorbed dose (98.9 %). Although the fast phase did not contribute substantially to the estimated renal dose, it had a high likelihood of interfering with the slow phase within the initial hours after injection. The unexpected dose underestimation which was observed with dosimetry calculations relying on these early time points, such as the reduced data model including the 1h measurement, could finally be explained with this discovery. These underestimations could lead to an over dosage of the therapy activity and thus to a critical radiation exposure to healthy tissue. By omitting this influenced measurement point and the solely use of the last three data points in the reduced data model, the dose delivering phase could be accurately displayed. With the insights gained in this study we were therefore able to develop a dosimetry model and workflow with increased robustness and higher confidence in the reported dose estimates, which at the same time relied on fewer measurements and therefore provided a significant reduction of work load for the staff and overall burden for the patients. This model was then applied in the dose assessment of the new radiopharmaceutical Lu-177-PSMA to avoid the above reported temporal interference effects. Fur

  7. Favourable outcomes of {sup 177}Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Hofman, Michael S.; Kong, Grace; Akhurst, Timothy; Eu, Peter [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Peter MacCallum Cancer Centre, Neuroendocrine Tumour Service, Melbourne (Australia); Michael, Michael [University of Medicine, Department of Medicine, Melbourne (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Zannino, Diana [Peter MacCallum Cancer Centre, Biostatistics and Clinical Trials, Melbourne (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Peter MacCallum Cancer Centre, Neuroendocrine Tumour Service, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia)

    2014-09-11

    Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear. This retrospective study assessed the outcomes of patients with FDG-avid NET treated with PRCRT. Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with 5-fluorouracil in 52 patients selected for treatment on the basis of somatostatin-receptor imaging without spatially discordant FDG-avid disease. Of the cohort, 67 % had received prior chemotherapy. Overall survival (OS) and progression-free survival (PFS) were also analysed. PRCRT was well tolerated with negligible grade 3/4 toxicities. After a median follow-up period of 36 months, the median OS was not achieved with a median PFS of 48 months. At 3 months after completion of PRCRT 2 % of patients showed a complete anatomical response, 28 % a partial response, 68 % stable disease, and only 2 % progression. On FDG PET/CT, 27 % achieved a complete metabolic response during the follow-up period. A biochemical response (>25 % fall in chromogranin-A levels) was seen in 45 %. PRCRT is an effective treatment in patients with FDG-avid NET, even in patients who have failed conventional therapies. Given apparently higher response rates than with alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality in this patient population. (orig.)

  8. Ad Libitum

    Index Scriptorium Estoniae

    2001-01-01

    20. mai. Segakoor Ad Libitum laulis Niguliste Muuseum-kontserdisaalis. Dirigendid Alice Pehk ja Kaie Viigipuu. Kaastegev Tiit Kiik (orel). Esitati koorimuusikat renessansist tänapäevani ning prantsuse orelimuusikat : [täistekst

  9. Adding Ajax

    CERN Document Server

    Powers, Shelley

    2007-01-01

    Ajax can bring many advantages to an existing web application without forcing you to redo the whole thing. This book explains how you can add Ajax to enhance, rather than replace, the way your application works. For instance, if you have a traditional web application based on submitting a form to update a table, you can enhance it by adding the capability to update the table with changes to the form fields, without actually having to submit the form. That's just one example.Adding Ajax is for those of you more interested in extending existing applications than in creating Rich Internet Applica

  10. Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole, a potential dopamine D{sub 4} receptor radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gu-Cai; Zhang, Ru [Hunan Institute of Engineering, Hunan Xiangtan (China). College of Chemistry and Chemical Engineering; Xia, Jiao-yun [Changsha Univ. of Science and Technology (China). School of Chemistry and Biology Engineering

    2016-07-01

    The dopamine D{sub 4} receptor has been shown to play important roles in some central nervous system pathologies. Specific radioligands for the D{sub 4} receptor may be useful to understand the function of the D{sub 4} receptor and its correlations with various disorders. 2-(3-(4-(4-[{sup 18}F]Fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole ([{sup 18}F]4) was synthesized through a one-pot two-step procedure with total yield 18.6% (decay corrected). The specific activity of the radioligand was 112 GBq/μmol and its radiochemical purity was >95.0%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding evaluation and the K{sub i} value for the D{sub 4} receptor was determined to be 2.9±0.2 nM, and its selectivity for the dopamine D{sub 4} receptor is 709-fold versus D{sub 2long} receptor, 823-fold versus D{sub 3} receptor. The partition coefficient (Log D) of it was determined to be 2.6±0.1 through octanol-water partition experiment. The ligand presents desirable combination of lipophilicity, affinity and selectivity for the dopamine D{sub 4} receptor. The results suggested that the radioligand shows promises for the in vivo study of the dopamine D{sub 4} receptor.

  11. Separation of no-carrier-added {sup 203}Pb, a surrogate radioisotope, from proton irradiated {sup nat}Tl{sub 2}CO{sub 3} target using calcium alginate hydrogel beads

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Kangkana; Sen, Kamalika [Univ. of Calcutta, Kolkata (India). Dept. of Chemistry; Lahiri, Susanta [Saha Institute of Nuclear Physics, Kolkata (India)

    2016-07-01

    {sup 203}Pb is a promising radioisotope in the field of medical science as an imaging surrogate of {sup 212}Pb. In the present investigation {sup 203}Pb was produced by proton irradiation of natural Tl{sub 2}CO{sub 3} target and was separated from the bulk Tl target using calcium alginate (CA) hydrogel beads with a high separation factor (3.8 x 10{sup 4} at 10{sup -3} M HNO{sub 3}). During the separation process {sup 203}Pb was encapsulated in CA beads and desorption of the radioisotope could only be achieved in 1M HNO{sub 3}. Possibility of Tl uptake was also checked in Fe doped CA (Fe-CA) beads after oxidation of Tl(I) to Tl(III) by sodium bismuthate. No significant uptake of Tl(III) was noticed in the Fe-CA beads. The matrix is therefore suitable for isolation of {sup 203}Pb from the target as well as its storage in the bead for therapeutic as well as diagnostic purpose.

  12. Targetry of MoO3 on a copper substrate for the no-carrier-added 94mTC production via 94Mo(p,n)94mTc reaction

    Institute of Scientific and Technical Information of China (English)

    SADEGHI Mahdi; KAKAVAND Tayeb; AREF Morteza; SARABADANI Parvin

    2009-01-01

    94mTc was produced via natMo(p,xn)94mTc reaction.Deposition of MoO3 on Cu substrate was carried out via two special sedimentation methods for the production of 94mTc.The 533 mg of MoO3,600 μL of collodium (nitrocellulose) and 3 mL of acetone were used to prepare a MoO3 layer of 11.69 cm2 and 45.81 mg.cm-2.Also,a MoO3 layer was prepared by 533 mg of MoO3,71.188 mg of methylcellulose and 4 mL of water.The targets were checked by SEM and thermal shock test.

  13. String Theory on AdS Spaces

    NARCIS (Netherlands)

    de Boer, J.

    2000-01-01

    In these notes we discuss various aspects of string theory in AdS spaces. We briefly review the formulation in terms of Green-Schwarz, NSR, and Berkovits variables, as well as the construction of exact conformal field theories with AdS backgrounds. Based on lectures given at the Kyoto YITP Workshop

  14. Online Ad Assignment with an Ad Exchange

    OpenAIRE

    Dvořák, Wolfgang; Henzinger, Monika

    2016-01-01

    Ad exchanges are becoming an increasingly popular way to sell advertisement slots on the internet. An ad exchange is basically a spot market for ad impressions. A publisher who has already signed contracts reserving advertisement impressions on his pages can choose between assigning a new ad impression for a new page view to a contracted advertiser or to sell it at an ad exchange. This leads to an online revenue maximization problem for the publisher. Given a new impression to sell decide whe...

  15. Segmented Strings in $AdS_3$

    CERN Document Server

    Callebaut, Nele; Samberg, Andreas; Toldo, Chiara

    2015-01-01

    We study segmented strings in flat space and in $AdS_3$. In flat space, these well known classical motions describe strings which at any instant of time are piecewise linear. In $AdS_3$, the worldsheet is composed of faces each of which is a region bounded by null geodesics in an $AdS_2$ subspace of $AdS_3$. The time evolution can be described by specifying the null geodesic motion of kinks in the string at which two segments are joined. The outcome of collisions of kinks on the worldsheet can be worked out essentially using considerations of causality. We study several examples of closed segmented strings in $AdS_3$ and find an unexpected quasi-periodic behavior. We also work out a WKB analysis of quantum states of yo-yo strings in $AdS_3$ and find a logarithmic term reminiscent of the logarithmic twist of string states on the leading Regge trajectory.

  16. Polarised black holes in AdS

    Science.gov (United States)

    Costa, Miguel S.; Greenspan, Lauren; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-06-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global AdS 4 with conformal boundary {S}2× {{{R}}}t. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic AdS behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an AdS soliton that includes the full backreaction of the electric field on the AdS geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both AdS soliton and black hole phases. The corresponding phase diagram generalizes the Hawking-Page phase transition. The AdS soliton dominates the low temperature phase and the black hole the high temperature phase, with a critical temperature that decreases as the external electric field increases. Finally, we consider the simple case of a free charged scalar field on {S}2× {{{R}}}t with conformal coupling. For a field in the SU(N ) adjoint representation we compare the phase diagram with the above gravitational system.

  17. Polarised Black Holes in AdS

    CERN Document Server

    Costa, Miguel S.; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-01-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global $AdS_{4}$ with conformal boundary $S^{2}\\times\\mathbb{R}_{t}$. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic $AdS$ behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an $AdS$ soliton that includes the full backreaction of the electric field on the $AdS$ geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both $AdS$ soliton and black hole phases. The corresponding phase diagram generalizes the Hawkin...

  18. Constructing Lifshitz solutions from AdS

    CERN Document Server

    Cassani, Davide

    2011-01-01

    Under general assumptions, we show that a gravitational theory in d+1 dimensions admitting an AdS solution can be reduced to a d-dimensional theory containing a Lifshitz solution with dynamical exponent z=2. Working in a d=4, N=2 supergravity setup, we prove that if the AdS background is N=2 supersymmetric, then the Lifshitz geometry preserves 1/4 of the supercharges, and we construct the corresponding Killing spinors. We illustrate these results in examples from supersymmetric consistent truncations of type IIB supergravity, enhancing the class of known 4-dimensional Lifshitz solutions of string theory. As a byproduct, we find a new AdS4 x S1 x T(1,1) solution of type IIB.

  19. Ad Hoc网络%Ad Hoc Network

    Institute of Scientific and Technical Information of China (English)

    王海涛

    2005-01-01

    首先介绍了Ad Hoc网络的基本概念、技术特点以及关键技术等,然后较为全面地归纳了Ad Hoc网络的典型应用,最后讨论了Ad Hoc网络的发展趋势和有待解决的问题.

  20. AdS orbifolds and Penrose limits

    Energy Technology Data Exchange (ETDEWEB)

    Alishahiha, Mohsen; Sheikh-Jabbari, Mohammad M.; Tatar, Radu

    2002-12-09

    In this paper we study the Penrose limit of AdS{sub 5} orbifolds. The orbifold can be either in the pure spatial directions or space and time directions. For the AdS{sub 5}/{Lambda} x S{sup 5} spatial orbifold we observe that after the Penrose limit we obtain the same result as the Penrose limit of AdS{sub 5} x S{sup 5}/{Lambda}. We identify the corresponding BMN operators in terms of operators of the gauge theory on R x S{sup 3}/{Lambda}. The semi-classical description of rotating strings in these backgrounds have also been studied. For the spatial AdS orbifold we show that in the quadratic order the obtained action for the fluctuations is the same as that in S{sup 5} orbifold, however, the higher loop correction can distinguish between two cases.

  1. Superradiant instability in AdS

    CERN Document Server

    Ganchev, Bogdan

    2016-01-01

    The phenomenon of superradiance in the context of asymptotically global AdS spacetimes is investigated with particular accent on its effect on the stability of the systems under consideration. To this end, the concept of an asymptotically AdS spacetime is explained, together with its implications on the boundary conditions at $\\mathcal{I}$, as well as the Newman-Penrose-Teukolsky formalism, whereby the Teukolsky master equation in a most general form for Kerr-AdS is given. Furthermore, work done in the cases of RN-AdS and Kerr-AdS is laid out in a concise manner, putting emphasis on the important steps taken in determining the endpoint of the superradiant instability in the two configurations. For the former this turns out to be a black hole with reduced charge and a static charged scalar condensate around it, whereas for the latter two of the more probable outcomes are presented, both of which imply a violation of one of the cosmic censorships.

  2. Lorentzian AdS, Wormholes and Holography

    CERN Document Server

    Arias, Raul E; Silva, Guillermo A

    2011-01-01

    We investigate the structure of two point functions for the QFT dual to an asymptotically Lorentzian AdS-wormhole. The bulk geometry is a solution of 5-dimensional second order Einstein Gauss Bonnet gravity and causally connects two asymptotically AdS space times. We revisit the GKPW prescription for computing two-point correlation functions for dual QFT operators O in Lorentzian signature and we propose to express the bulk fields in terms of the independent boundary values phi_0^\\pm at each of the two asymptotic AdS regions, along the way we exhibit how the ambiguity of normalizable modes in the bulk, related to initial and final states, show up in the computations. The independent boundary values are interpreted as sources for dual operators O^\\pm and we argue that, apart from the possibility of entanglement, there exists a coupling between the degrees of freedom leaving at each boundary. The AdS_(1+1) geometry is also discussed in view of its similar boundary structure. Based on the analysis, we propose a ...

  3. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  4. Peptide Receptor Radionuclide Therapy with (90)Y-DOTATOC and (177)Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  5. Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with {sup 177}Lu-D OTATATE

    Energy Technology Data Exchange (ETDEWEB)

    Sansovini, Maddalena; Severi, Stefano; Ianniello, Annarita; Nicolini, Silvia; Fantini, Lorenzo; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola (Italy); Mezzenga, Emilio [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Ferroni, Fabio [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Radiology Unit, Meldola (Italy); Scarpi, Emanuela; Monti, Manuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Cingarlini, Sara [University of Verona, Department of Oncology, Verona Comprehensive Cancer Network, G.B. Rossi Hospital, Verona (Italy); Grana, Chiara Maria; Bodei, Lisa [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy)

    2017-03-15

    Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs. From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6-8 weeks), according to kidney and bone marrow parameters. Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P < 0.0002), regardless of the total activity administered. Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting. (orig.)

  6. 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies

    National Research Council Canada - National Science Library

    Weineisen, Martina; Schottelius, Margret; Simecek, Jakub; Baum, Richard P; Yildiz, Akin; Beykan, Seval; Kulkarni, Harshad R; Lassmann, Michael; Klette, Ingo; Eiber, Matthias; Schwaiger, Markus; Wester, Hans-Jürgen

    2015-01-01

    ...) in metastatic prostate cancer (PC), the goal of this study was the development, preclinical evaluation, and first proof-of-concept investigation of a PSMA inhibitor for imaging and therapy (PSMA I&T) for (68)Ga-based PET and (177...

  7. (99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

    Science.gov (United States)

    Basu, Sandip; Joshi, Amit

    2014-07-01

    The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.

  8. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2015-09-01

    Sincerely , Rosemary Kraemer, Ph.D. Director, Human Research Protections Program Please note the following important information about this approval...sciences journal literature , and be made publicly available within twelve months of publication. The Library and RASP have prepared general information

  9. Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy.

    NARCIS (Netherlands)

    Melis, M.; Swart, J.; Visser, M. de; Berndsen, S.C.; Koelewijn, S.; Valkema, R.; Boerman, O.C.; Krenning, E.P.; Jong, M. de

    2010-01-01

    High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with beta-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal

  10. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Biochemically Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2010-09-01

    review on hold pending additional funding - University of Medicine and Dentistry , New Jersey – scientific review - Nevada Cancer Institute – scientific...BIOCHEMICALLY RELAPSED PROSTATE CANCER AFTER LOCAL THERAPY Scott T. Tagawa, Joseph Osborne, Paul J. Christos, Shankar Vallabhajosula, Kristen Petrillo

  11. Boson Stars in AdS

    CERN Document Server

    Buchel, Alex; Lehner, Luis

    2013-01-01

    We construct boson stars in global Anti de Sitter (AdS) space and study their stability. Linear perturbation results suggest that the ground state along with the first three excited state boson stars are stable. We evolve some of these solutions and study their nonlinear stability in light of recent work \\cite{Bizon:2011gg} arguing that a weakly turbulent instability drives scalar perturbations of AdS to black hole formation. However evolutions suggest that boson stars are nonlinearly stable and immune to the instability for sufficiently small perturbation. Furthermore, these studies find other families of initial data which similarly avoid the instability for sufficiently weak parameters. Heuristically, we argue that initial data families with widely distributed mass-energy distort the spacetime sufficiently to oppose the coherent amplification favored by the instability. From the dual CFT perspective our findings suggest that there exist families of rather generic initial conditions in strongly coupled CFT ...

  12. AdS solutions through transgression

    Energy Technology Data Exchange (ETDEWEB)

    Donos, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Gauntlett, J.P. [Imperial College, London (United Kingdom). Blackett Lab.]|[Imperial College, London (United Kingdom). The Institute for Mathematical Sciences; Kim, Nakwoo [Kyung Hee Univ., Seoul (Korea). Dept. of Physics and Research Inst. of Basic Science

    2008-07-15

    We present new classes of explicit supersymmetric AdS{sub 3} solutions of type IIB supergravity with non-vanishing five-form flux and AdS{sub 2} solutions of D=11 supergravity with electric four-form flux. The former are dual to two-dimensional SCFTs with (0,2) supersymmetry and the latter to supersymmetric quantum mechanics with two supercharges. We also investigate more general classes of AdS{sub 3} solutions of type IIB supergravity and AdS{sub 2} solutions of D=11 supergravity which in addition have non-vanishing three-form flux and magnetic four-form flux, respectively. The construction of these more general solutions makes essential use of the Chern-Simons or ''transgression'' terms in the Bianchi identity or the equation of motion of the field strengths in the supergravity theories. We construct infinite new classes of explicit examples and for some of the type IIB solutions determine the central charge of the dual SCFTs. The type IIB solutions with non-vanishing three-form flux that we construct include a two-torus, and after two T-dualities and an S-duality, we obtain new AdS3 solutions with only the NS fields being non-trivial. (orig.)

  13. Refined Holographic Entanglement Entropy for the AdS Solitons and AdS black Holes

    CERN Document Server

    Ishihara, Masafumi; Ning, Bo

    2012-01-01

    We consider the refinement of the holographic entanglement entropy on a disk region for the holographic dual theories to the AdS solitons and AdS black holes, including the corrected ones by the Gauss-Bonnet term. The AdS soliton is dual to a gapped system with an IR fixed-point. The refinement is obtained by extracting the UV-independent piece of the holographic entanglement entropy. We then study the renormalization group (RG) flow of the refinement by tuning the linear size of the chosen disk region. Our main results are (i) the RG flow of the refinement decreases monotonically for most of the cases; (ii) there is no topological entanglement entropy for AdS$_5$ soliton even with Gauss-Bonnet correction; (iii) for the AdS black holes, the refinement obeys the volume law at IR regime, and the transition between UV and IR regimes is a smooth crossover; however, the crossover will turn into phase transition by the Gauss-Bonnet correction; (iv) for the AdS solitons, there are discontinuous phase transitions bet...

  14. Predicting AD conversion

    DEFF Research Database (Denmark)

    Liu, Yawu; Mattila, Jussi; Ruiz, Miguel �ngel Mu�oz

    2013-01-01

    To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI...

  15. An AdS Crunch in Supergravity

    Science.gov (United States)

    Hertog, Thomas

    2004-12-01

    We review some properties of N=8 gauged supergravity in four dimensions with modified, but AdS invariant boundary conditions on the m2 = -2 scalars. There is a one-parameter class of asymptotic conditions on these fields and the metric components, for which the full AdS symmetry group is preserved. The generators of the asymptotic symmetries are finite, but acquire a contribution from the scalar fields. For a large class of such boundary conditions, we find there exist black holes with scalar hair that are specified by a single conserved charge. Since Schwarschild-AdS is a solution too for all boundary conditions, this provides an example of black hole non-uniqueness. We also show there exist solutions where smooth initial data evolve to a big crunch singularity. This opens up the possibility of using the dual conformal field theory to obtain a fully quantum description of the cosmological singularity, and we report on a preliminary study of this.

  16. Adding more value to added-value

    DEFF Research Database (Denmark)

    Marian, Livia

    regulation. The results of a qualitative concept test reveal positive attitudes towards the proposed production process. The discussions about fewer standards being sufficient or about options “in-between” conventional and organic standards indicate that the difference in production processes is noticed, yet...... it is probably valued less than expected. The added attributes need to be thoroughly considered when developing and marketing “organic plus” products, as their effect on other product characteristics (e.g. high prices) can detract from their added value....

  17. Probing crunching AdS cosmologies

    Science.gov (United States)

    Kumar, S. Prem; Vaganov, Vladislav

    2016-02-01

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of {N}=8 supergravity on AdS4, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor ã max. Radial geodesics connecting antipodal points necessarily have de Sitter energy Ɛ ≲ ã max, while geodesics with Ɛ > ã max terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved "outward" in the Penrose diagram for the deformed AdS backgrounds, and thus geodesic limits of the antipodal correlators do not directly probe the crunch. Beyond the geodesic limit, we point out that the scalar wave equation, analytically continued into the FRW patch, has a potential which is singular at the crunch along with complex WKB turning points in the vicinity of the FRW crunch. We then argue that the frequency space Green's function has a branch point determined by ã max which corresponds to the lowest quasinormal frequency.

  18. The political attack ad

    Directory of Open Access Journals (Sweden)

    Palma Peña-Jiménez, Ph.D.

    2011-01-01

    Full Text Available During election campaigns the political spot has a clear objective: to win votes. This message is communicated to the electorate through television and Internet, and usually presents a negative approach, which includes a direct critical message against the opponent, rather than an exposition of proposals. This article is focused on the analysis of the campaign attack video ad purposely created to encourage the disapproval of the political opponent among voters. These ads focus on discrediting the opponent, many times, through the transmission of ad hominem messages, instead of disseminating the potential of the political party and the virtues and manifesto of its candidate. The article reviews the development of the attack ad since its first appearance, which in Spain dates back to 1996, when the famous Doberman ad was broadcast, and examines the most memorable campaign attack ads.

  19. Probing crunching AdS cosmologies

    CERN Document Server

    Kumar, S Prem

    2015-01-01

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of N=8 supergravity on AdS_4, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor a_{max} . Radial geodesics connecting antipodal points necessarily have de Sitter energy E \\leq a_{max}, while geodesics with E > a_{max} terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved "outw...

  20. Holography of AdS vacuum bubbles

    Energy Technology Data Exchange (ETDEWEB)

    Barbon, J.L.F. [Instituto de Fisica Teorica IFT UAM/CSIC, Cantoblanco, Madrid 28049 (Spain); Rabinovici, E. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel)

    2011-07-15

    We consider the fate of AdS vacua connected by tunneling events. A precise holographic dual of thin-walled Coleman-de Luccia bounces is proposed in terms of Fubini instantons in an unstable CFT. This proposal is backed by several qualitative and quantitative checks, including the precise calculation of the instanton action appearing in evaluating the decay rate. Big crunches manifest themselves as time dependent processes which reach the boundary of field space in a finite time. The infinite energy difference involved is identified on the boundary and highlights the ill-defined nature of the bulk setup. We propose a qualitative scenario in which the crunch is resolved by stabilizing the CFT, so that all attempts at crunching always end up shielded from the boundary by the formation of black hole horizons. In all these well defined bulk processes the configurations have the same asymptotics and are finite energy excitations.

  1. Twistor methods for AdS$_5$

    CERN Document Server

    Adamo, Tim; Williams, Jack

    2016-01-01

    We consider the application of twistor theory to five-dimensional anti-de Sitter space. The twistor space of AdS$_5$ is the same as the ambitwistor space of the four-dimensional conformal boundary; the geometry of this correspondence is reviewed for both the bulk and boundary. A Penrose transform allows us to describe free bulk fields, with or without mass, in terms of data on twistor space. Explicit representatives for the bulk-to-boundary propagators of scalars and spinors are constructed, along with twistor action functionals for the free theories. Evaluating these twistor actions on bulk-to-boundary propagators is shown to produce the correct two-point functions.

  2. AdS2 holographic dictionary

    Science.gov (United States)

    Cvetič, Mirjam; Papadimitriou, Ioannis

    2016-12-01

    We construct the holographic dictionary for both running and constant dilaton solutions of the two dimensional Einstein-Maxwell-Dilaton theory that is obtained by a circle reduction from Einstein-Hilbert gravity with negative cosmological constant in three dimensions. This specific model ensures that the dual theory has a well defined ultraviolet completion in terms of a two dimensional conformal field theory, but our results apply qualitatively to a wider class of two dimensional dilaton gravity theories. For each type of solutions we perform holographic renormalization, compute the exact renormalized one-point functions in the presence of arbitrary sources, and derive the asymptotic symmetries and the corresponding conserved charges. In both cases we find that the scalar operator dual to the dilaton plays a crucial role in the description of the dynamics. Its source gives rise to a matter conformal anomaly for the running dilaton solutions, while its expectation value is the only non trivial observable for constant dilaton solutions. The role of this operator has been largely overlooked in the literature. We further show that the only non trivial conserved charges for running dilaton solutions are the mass and the electric charge, while for constant dilaton solutions only the electric charge is non zero. However, by uplifting the solutions to three dimensions we show that constant dilaton solutions can support non trivial extended symmetry algebras, including the one found by Compère, Song and Strominger [1], in agreement with the results of Castro and Song [2]. Finally, we demonstrate that any solution of this specific dilaton gravity model can be uplifted to a family of asymptotically AdS2 × S 2 or conformally AdS2 × S 2 solutions of the STU model in four dimensions, including non extremal black holes. The four dimensional solutions obtained by uplifting the running dilaton solutions coincide with the so called `subtracted geometries', while those obtained

  3. Skil problemerne ad

    DEFF Research Database (Denmark)

    Kaspersen, Peter

    2007-01-01

    På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger.......På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger....

  4. Probing crunching AdS cosmologies

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S. Prem; Vaganov, Vladislav [Department of Physics, Swansea University,Singleton Park, Swansea SA2 8PP (United Kingdom)

    2016-02-03

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of N=8 supergravity on AdS{sub 4}, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor ã{sub max}. Radial geodesics connecting antipodal points necessarily have de Sitter energy E≲ã{sub max}, while geodesics with E>ã{sub max} terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved “outward” in the Penrose diagram for the deformed AdS backgrounds, and thus geodesic limits of the antipodal correlators do not directly probe the crunch. Beyond the geodesic limit, we point out that the scalar wave equation, analytically continued into the FRW patch, has a potential which is singular at the crunch along with complex WKB turning points in the vicinity of the FRW crunch. We then argue that the frequency space Green’s function has a branch point determined by ã{sub max} which corresponds to the lowest quasinormal frequency.

  5. Mobile ad hoc networking

    CERN Document Server

    John Wiley & Sons

    2004-01-01

    "Assimilating the most up-to-date information on research and development activities in this rapidly growing area, Mobile Ad Hoc Networking covers physical, data link, network, and transport layers, as well as application, security, simulation, and power management issues in sensor, local area, personal, and mobile ad hoc networks. Each of the book's sixteen chapters has been written by a top expert and discusses in-depth the most important topics in the field. Mobile Ad Hoc Networking is an excellent reference and guide for professionals seeking an in-depth examination of topics that also provides a comprehensive overview of the current state-of-the-art."--Jacket.

  6. Antiproton-Decelerator (AD)

    CERN Multimedia

    Laurent Guiraud

    1998-01-01

    When the Low-Energy Antiproton Ring (LEAR) was stopped in 1996, because of its costly operation, a cheaper way of continuing low-energy antiproton physics was sought. The Antiproton-Collector (AC), added in 1987 to the Antiproton Accumulator (AA) to provide a tenfold intensity increase, was converted into the Antiproton-Decelerator (AD). Antiprotons from the target at 3.5 GeV/c are decelerated to 100 MeV/c, and fast-ejected to the experiments. Major changes were necessary. Above all, the conversion from a constant-field machine to one with a magnetic cycle, modulating the field by an impressive factor 35. New systems for stochastic and electron cooling had to be added. Beam diagnostics at an intensity of only 2E7 antiprotons was a challenge. In 2000, the AD began delivery of antiprotons to the experiments.

  7. Value Adding Management

    DEFF Research Database (Denmark)

    Jensen, Per Anker; Katchamart, Akarapong

    2011-01-01

    Purpose: To investigate how Facilities Management (FM) can add value and develop a management concept that can assist facilities managers in implementing value adding strategies and practices. Theory: The study is based on the management model for FM included in the European FM standards, recent...... theories on added value of FM and real estate and the related concept of Value Management from building projects. The study is related to the EuroFM research group on The Added Value of FM. Design/methodology/approach: The study outlines a preliminary theoretical based management concept, which...... is investigated, tested and discussed based on a case study of an international corporation. Findings: The study shows that the management model for FM creates a relevant starting point but also that stakeholder and relationship management is an essential aspect of Value Adding Management. The case study confirms...

  8. AdS_3: the NHEK generation

    CERN Document Server

    Bena, Iosif; Puhm, Andrea

    2015-01-01

    It was argued in arXiv:1203.4227 that the five-dimensional near-horizon extremal Kerr (NHEK) geometry can be embedded in String Theory as the infrared region of an infinite family of non-supersymmetric geometries that have D1, D5, momentum and KK monopole charges. We show that there exists a method to embed these geometries into asymptotically-AdS_3 x S^3/Z_N solutions, and hence to obtain infinite families of flows whose infrared is NHEK. This indicates that the CFT dual to the NHEK geometry is the IR fixed point of a Renormalization Group flow from a known local UV CFT and opens the door to its explicit construction.

  9. Dynamic ad hoc networks

    CERN Document Server

    Rashvand, Habib

    2013-01-01

    Motivated by the exciting new application paradigm of using amalgamated technologies of the Internet and wireless, the next generation communication networks (also called 'ubiquitous', 'complex' and 'unstructured' networking) are changing the way we develop and apply our future systems and services at home and on local, national and global scales. Whatever the interconnection - a WiMAX enabled networked mobile vehicle, MEMS or nanotechnology enabled distributed sensor systems, Vehicular Ad hoc Networking (VANET) or Mobile Ad hoc Networking (MANET) - all can be classified under new networking s

  10. D-branes in Lorentzian AdS(3)

    CERN Document Server

    Israel, D

    2005-01-01

    We study the exact construction of D-branes in Lorentzian AdS(3). We start by defining a family of conformal field theories that gives a natural Euclidean version of the SL(2,R) CFT and does not correspond to H(3)+, the analytic continuation of AdS(3). We argue that one can recuperate the exact CFT results of Lorentzian AdS(3), upon an analytic continuation in the moduli space of these conformal field theories. Then we construct exact boundary states for various symmetric and symmetry-breaking D-branes in AdS(3).

  11. Localization on $AdS_2\\times S^1$

    CERN Document Server

    David, Justin R; Gupta, Rajesh Kumar; Narain, Kumar

    2016-01-01

    Conformal symmetry relates the metric on $AdS_2 \\times S^{1}$ to that of $S^3$. This implies that under a suitable choice of boundary conditions for fields on $AdS_2$ the partition function of conformal field theories on these spaces must agree which makes $AdS_2 \\times S^{1}$ a good testing ground to study localization on non-compact spaces. We study supersymmetry on $AdS_2\\times S^1$ and determine the localizing Lagrangian for ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2\\times S^1$. We evaluate the partition function of ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2 \\times S^1$ using localization, where the radius of $S^1$ is $q$ times that of $AdS_2$. With boundary conditions on $AdS_2\\times S^1$ which ensure that all the physical fields are normalizable and lie in the space of square integrable wave functions in $AdS_2$, the result for the partition function precisely agrees with that of the theory on the $q$-fold covering of $S^3$.

  12. Ads in Indonesia

    Directory of Open Access Journals (Sweden)

    Wulan Roro Retno

    2017-01-01

    Full Text Available Cosmetics industry created the beauty myth for women through advertising. A cosmetic ad in Indonesia has spread a new concept of white skin: East Asia beauty myth. The white concept of Asia white skin basically derived from colonial legacy. The purpose of the research was analyzing the beauty myth in Indonesia ads using postcolonial perspective. The principal result brought the discourse analysis and postcolonial perspective a new insight in communication research. Particularly on media and cultural studies. Major conclusions showed that the beauty myth since the Dutch colonial period never been change. The main concept is always in colonialism’s idea: “white is better”. The West is better than the East.

  13. Adding linear orders

    CERN Document Server

    Shelah, Saharon

    2011-01-01

    We address the following question: Can we expand an NIP theory by adding a linear order such that the expansion is still NIP? Easily, if acl(A)=A for all A, then this is true. Otherwise, we give counterexamples. More precisely, there is a totally categorical theory for which every expansion by a linear order has IP. There is also an \\omega-stable NDOP theory for which every expansion by a linear order interprets bounded arithmetic.

  14. AdS 3-manifolds and Higgs bundles

    DEFF Research Database (Denmark)

    Alessandrini, Daniele; Li, Qiongling

    2015-01-01

    In this paper we investigate the relationships between closed AdS 3-manifolds and Higgs bundles. We have a new way to construct AdS structures that allows us to see many of their properties explicitly, for example we can recover the very recent formula by Tholozan for the volumes. We also find...

  15. Pathologies in Lovelock AdS Black Branes and AdS/CFT

    CERN Document Server

    Takahashi, Tomohiro

    2011-01-01

    We study the pathologies in AdS black branes in Lovelock theory. More precisely, we examine the conditions that AdS black branes have the naked singularity, the ghost instability and the dynamical instability. From the point of view of the AdS/CFT correspondence, the pathologies in AdS black branes indicate the pathologies in the corresponding CFT. Hence, we need to be careful when we apply AdS/CFT in Lovelock theory to various phenomena such as the shear viscosity to entropy ratio in strongly coupled quantum filed theory.

  16. The effect of Ad

    Institute of Scientific and Technical Information of China (English)

    李小艳

    2010-01-01

    There is the trend that now people appreciate those who are slim and regard slim even thin people beautiful. The thinner a person is, the more beautiful. Women, born to pursuit beauty, try various means to follow the trend. We all watch TV, and find a lot of advertisements on diet. The effect of them is tremendous. We all know the fact that it is not at all the better mouse trap will catch mouse. The sales methods are more important. If an advertisement is very interesting and seemingly effective, people will be lured by the ad and then try some of the products.

  17. Management job ads

    DEFF Research Database (Denmark)

    2014-01-01

    The article asks whether it is not the responsibility of corporations to address the issue of women being underrepresented in Danish management jobs. In other words, it is argued that corporations should be encouraged to engage more actively in the recruitment of both men and women for management...... that this agreement reflects a high degree of conservatism in the system where men enjoy a considerable advantage and where procedures that ensure male dominance are perpetuated even in the linguistic and discursive construction of job ads....

  18. Eating ad Libitum

    DEFF Research Database (Denmark)

    Hillersdal, Line

    ask what make up food stuff and eaters in the meal tests? More specifically I explore a scientific testing of changes in taste preferences before and after weight-loss surgery using an ad libitum buffet with a selection of different foods and another testing the effect of exercise on appetite also...... an eater who: ”shouldn't restrain herself”. Practices of food and eating in the test meal I suggest, will allow us to tackle reductionism by showing the complex cultural context shaping clinical intervention....

  19. Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available 177Lu-DOTA-HH1 (177Lu-HH1 is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1 and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.

  20. Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma

    Science.gov (United States)

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Patzke, Sebastian; Fleten, Karianne G.; Didierlaurent, David; Pichard, Alexandre; Pouget, Jean Pierre; Dahle, Jostein

    2015-01-01

    177Lu-DOTA-HH1 (177Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab) and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1. PMID:26066655

  1. Value-Added Exchange Rates

    OpenAIRE

    Rudolfs Bems; Robert C. Johnson

    2012-01-01

    This paper updates the conceptual foundations for measuring real effective exchange rates (REERs) to allow for vertical specialization in trade. We derive a value-added REER describing how demand for the value added that a country produces changes as the price of its value added changes relative to competitors. We then compute this index for 42 countries from 1970-2009 using trade measured in value added terms and GDP deflators. There are substantial differences between value-added and conven...

  2. An $xp$ model on $AdS_2$ spacetime

    CERN Document Server

    Molina-Vilaplana, Javier

    2013-01-01

    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, equal in magnitude, given by a harmonic oscillator with a zero point energy parameterized by the AdS radius, measured in units of a fundamental length of the model. We also construct the generators of the isometry group SO(2,1) of the AdS$_2$ spacetime, and discuss the relation with conformal quantum mechanics.

  3. Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Hong-Chuan Yang

    2007-01-01

    Full Text Available We study the energy-efficient configuration of multihop paths with automatic repeat request (ARQ mechanism in wireless ad hoc networks. We adopt a cross-layer design approach and take both the quality of each radio hop and the battery capacity of each transmitting node into consideration. Under certain constraints on the maximum tolerable transmission delay and the required packet delivery ratio, we solve optimization problems to jointly schedule the transmitting power of each transmitting node and the retransmission limit over each hop. Numerical results demonstrate that the path configuration methods can either significantly reduce the average energy consumption per packet delivery or considerably extend the average lifetime of the multihop route.

  4. Dressing phases of AdS3/CFT2

    CERN Document Server

    Borsato, Riccardo; Sfondrini, Alessandro; Stefanski, Bogdan; Torrielli, Alessandro

    2013-01-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3 x S3 x T4 by solving the recently found crossing relations and studying their singularity structure. The two resulting phases present a novel structure with respect to the ones appearing in AdS5/CFT4 and AdS4/CFT3. In the strongly-coupled regime, their leading order reduces to the universal Arutyunov-Frolov-Staudacher phase as expected. We also compute their sub-leading order and compare it with recent one-loop perturbative results, and co

  5. Dressing phases of AdS3/CFT2

    Science.gov (United States)

    Borsato, Riccardo; Ohlsson Sax, Olof; Sfondrini, Alessandro; Stefański, Bogdan, Jr.; Torrielli, Alessandro

    2013-09-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3×S3×T4 by solving the recently found crossing relations and studying their singularity structure. The two resulting phases present a novel structure with respect to the ones appearing in AdS5/CFT4 and AdS4/CFT3. In the strongly coupled regime, their leading order reduces to the universal Arutyunov-Frolov-Staudacher phase as expected. We also compute their subleading order and compare it with recent one-loop perturbative results and comment on their weak-coupling expansion.

  6. Quantum Field Theory and Unification in AdS5

    CERN Document Server

    Randall, Lisa; Randall, Lisa; Schwartz, Matthew D.

    2001-01-01

    We consider gauge bosons in the bulk of AdS5 in a two-brane theory that addresses the hierarchy problem. We show such a theory can be consistent with gauge coupling unification at a high scale. We discuss subtleties in this calculation and show how to regulate consistently in a bounded AdS5 background. Our regularization is guided by the holographic dual of the calculation.

  7. Chaos and hydrodynamics near AdS$_2$

    CERN Document Server

    Jensen, Kristan

    2016-01-01

    We revisit AdS$_2$ holography with the Sachdev-Ye-Kitaev models in mind. Our main result is to rewrite a generic theory of gravity near an AdS$_2$ throat as a novel hydrodynamics coupled to the correlation functions of a conformal quantum mechanics. This gives a prescription for the computation of $n$-point functions in the dual quantum mechanics. We thereby find that the dual is maximally chaotic.

  8. Supersymmetry of AdS and flat IIB backgrounds

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2015-02-01

    We present a systematic description of all warped AdS n × w M 10- n and IIB backgrounds and identify the a priori number of supersymmetries N preserved by these solutions. In particular, we find that the AdS n backgrounds preserve for n ≤ 4 and for 4 < n ≤ 6 supersymmetries and for suitably restricted. In addition under some assumptions required for the applicability of the maximum principle, we demonstrate that the Killing spinors of AdS n backgrounds can be identified with the zero modes of Dirac-like operators on M 10- n establishing a new class of Lichnerowicz type theorems. Furthermore, we adapt some of these results to backgrounds with fluxes by taking the AdS radius to infinity. We find that these backgrounds preserve for 2 < n ≤ 4 and for 4 < n ≤ 7 supersymmetries. We also demonstrate that the Killing spinors of AdS n × w M 10- n do not factorize into Killing spinors on AdS n and Killing spinors on M 10- n .

  9. ad hoc networks

    Directory of Open Access Journals (Sweden)

    Blanca Alicia Correa

    2007-01-01

    Full Text Available Los métodos de agrupamiento permiten que las MANET (redes móviles ad hoc presenten un mejor desempeño en cuanto a la rapidez de conexión, el enrutamiento y el manejo de la topología. En este trabajo se presenta una revisión sobre las técnicas de agrupamiento para MANET. Se introducen algunos temas preliminares que forman la base para el desarrollo de los algoritmos de agrupamiento, tales como: la topología de la red, el enrutamiento, la teoría de grafos y los algoritmos de movilidad. Adicionalmente, se describen algunas de las técnicas de agrupamiento más conocidas como Lowest-ID heuristic, Highest degree heuristic, DMAC (distributed mobility-adaptive clustering, WCA (weighted clustering algorithm, entre otros. El propósito central es ilustrar los conceptos principales respecto a las técnicas de agrupamiento en MANET.

  10. Action growth for AdS black holes

    Science.gov (United States)

    Cai, Rong-Gen; Ruan, Shan-Ming; Wang, Shao-Jiang; Yang, Run-Qiu; Peng, Rong-Hui

    2016-09-01

    Recently a Complexity-Action (CA) duality conjecture has been proposed, which relates the quantum complexity of a holographic boundary state to the action of a Wheeler-DeWitt (WDW) patch in the anti-de Sitter (AdS) bulk. In this paper we further investigate the duality conjecture for stationary AdS black holes and derive some exact results for the growth rate of action within the Wheeler-DeWitt (WDW) patch at late time approximation, which is supposed to be dual to the growth rate of quantum complexity of holographic state. Based on the results from the general D-dimensional Reissner-Nordström (RN)-AdS black hole, rotating/charged Bañados-Teitelboim-Zanelli (BTZ) black hole, Kerr-AdS black hole and charged Gauss-Bonnet-AdS black hole, we present a universal formula for the action growth expressed in terms of some thermodynamical quantities associated with the outer and inner horizons of the AdS black holes. And we leave the conjecture unchanged that the stationary AdS black hole in Einstein gravity is the fastest computer in nature.

  11. AdS_5 Black Holes with Fermionic Hair

    CERN Document Server

    Burrington, B A; Sabra, W A; Burrington, Benjamin A.; Liu, James T.

    2004-01-01

    The study of new BPS objects in AdS_5 has led to a deeper understanding of AdS/CFT. To help complete this picture, and to fully explore the consequences of the supersymmetry algebra, it is also important to obtain new solutions with bulk fermions turned on. In this paper we construct superpartners of the 1/2 BPS black hole in AdS_5 using a natural set of fermion zero modes. We demonstrate that these superpartners, carrying fermionic hair, have conserved charges differing from the original bosonic counterpart. To do so, we find the R-charge and dipole moment of the new system, as well as the mass and angular momentum, defined through the boundary stress tensor. The complete set of superpartners fits nicely into a chiral representation of AdS_5 supersymmetry, and the spinning solutions have the expected gyromagnetic ratio, g=1.

  12. Complexity Growth for AdS Black Holes

    CERN Document Server

    Cai, Rong-Gen; Wang, Shao-Jiang; Yang, Run-Qiu; Peng, Rong-Hui

    2016-01-01

    We further investigate the Complexity-Action (CA) duality conjecture for stationary anti de-Sitter (AdS) black holes and derive some exact results for the growth rate of action within Wheeler-DeWitt (WDW) patch at late time approximation, which is dual to the growth rate of quantum complexity of holographic state. Based on the results from the general $D$-dimensional Reissner-Nordstr\\"{o}m (RN)-AdS black hole, rotating/charged Ba\\~{n}ados-Teitelboim-Zanelli (BTZ) black hole, Kerr-AdS black hole and charged Gauss-Bonnet-AdS black hole, we present a new complexity bound but leave unchanged the conjecture that the stationary AdS black hole in Einstein gravity is the fastest computer in nature.

  13. Constructing the AdS dual of a Fermi liquid: AdS Black holes with Dirac hair

    CERN Document Server

    \\vCubrović, Mihailo; Schalm, Koenraad

    2010-01-01

    We provide new evidence that the holographic dual to a strongly coupled charged Fermi Liquid has a non-zero fermion density in the bulk. We show that the pole-strength of the stable quasiparticle characterizing the Fermi surface is encoded in the spatially averaged AdS probability density of a single normalizable fermion wavefunction in AdS. Recalling Migdal's theorem which relates the pole strength to the Fermi-Dirac characteristic discontinuity in the number density at $\\ome_F$, we conclude that the AdS dual of a Fermi liquid is described by occupied on-shell fermionic modes in AdS. Encoding the occupied levels in the total probability density of the fermion field directly, we show that an AdS Reissner-Nordstr\\"{o}m black hole in a theory with charged fermions has a critical temperature, at which the system undergoes a first-order transition to a black hole with a non-vanishing profile for the bulk fermion field. Thermodynamics and spectral analysis confirm that the solution with non-zero AdS fermion-profil...

  14. Global geometric properties of AdS space and the AdS/CFT correspondence

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The Poisson kernels and relations between them for a massive scalar field in a unit ball Bn with Hua's metric and conformal flat metric are obtained by describing the Bn as a submanifold of an (n+1)-dimensional embedding space. Global geometric properties of the AdS space are discussed. We show that the(n+1)-dimensional AdS space AdSn+1 is isomorphic to RP1×Bn and boundary of the AdS is isomorphic to RP1×Sn-1. Bulk-boundary propagator and the AdS/CFT like correspondence are demonstrated based on these global geometric properties of the RP1×Bn.

  15. Different views of AEGIS / AD-6 Experiment (AD facility) AD-6

    CERN Multimedia

    Maximilien Brice

    2012-01-01

    Different views of AEGIS / AD-6 Experiment (AD facility) in July of 2012. The visible parts are the positron accumulator (blue structures on top of of the antiproton extraction line) and the 5T magnet which traps the antiprotons.

  16. AdS-Carroll Branes

    CERN Document Server

    Clark, T E

    2016-01-01

    Coset methods are used to determine the action of a co-dimension one brane (domain wall) embedded in (d+1)-dimensional AdS space in the Carroll limit in which the speed of light goes to zero. The action is invariant under the non-linearly realized symmetries of the AdS-Carroll spacetime. The Nambu-Goldstone field exhibits a static spatial distribution for the brane with a time varying momentum density related to the brane's spatial shape as well as the AdS-C geometry. The AdS-C vector field dual theory is obtained.

  17. Entanglement entropy for free scalar fields in AdS

    CERN Document Server

    Sugishita, Sotaro

    2016-01-01

    We compute entanglement entropy for free massive scalar fields in anti-de Sitter (AdS) space. The entangling surface is a minimal surface whose boundary is a sphere at the boundary of AdS. The entropy can be evaluated from the thermal free energy of the fields on a topological black hole by using the replica method. In odd-dimensional AdS, exact expressions of the Renyi entropy S_n are obtained for arbitrary n. We also evaluate 1-loop corrections coming from the scalar fields to holographic entanglement entropy. Applying the results, we compute the leading difference of entanglement entropy between two holographic CFTs related by a renormalization group flow triggered by a double trace deformation. The difference is proportional to the shift of a central charge under the flow.

  18. Microstates at the boundary of AdS

    CERN Document Server

    Mathur, Samir D

    2011-01-01

    The bound states of the D1D5 brane system have a known gravitational description: flat asymptotics, an anti-de Sitter region, and a 'cap' ending the AdS region. We construct perturbations that correspond to the action of chiral algebra generators on Ramond ground states of D1D5 branes. Abstract arguments in the literature suggest that the perturbation should be pure gauge in the AdS region; our perturbation indeed has this structure, with the nontrivial deformation of the geometry occurring at the 'neck' between the AdS region and asymptotic infinity. This 'non-gauge' deformation is needed to provide the nonzero energy and momentum carried by the perturbation. We also suggest implications this structure may have for the majority of microstates which live at the cap.

  19. Detailed ultraviolet asymptotics for AdS scalar field perturbations

    CERN Document Server

    Evnin, Oleg

    2016-01-01

    We present a range of methods suitable for accurate evaluation of the leading asymptotics for integrals of products of Jacobi polynomials in limits when the degrees of some or all polynomials inside the integral become large. The structures in question have recently emerged in the context of effective descriptions of small amplitude perturbations in anti-de Sitter (AdS) spacetime. The limit of high degree polynomials corresponds in this situation to effective interactions involving extreme short-wavelength modes, whose dynamics is crucial for the turbulent instabilities that determine the ultimate fate of small AdS perturbations. We explicitly apply the relevant asymptotic techniques to the case of a self-interacting probe scalar field in AdS and extract a detailed form of the leading large degree behavior, including closed form analytic expressions for the numerical coefficients appearing in the asymptotics.

  20. Detailed ultraviolet asymptotics for AdS scalar field perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Evnin, Oleg [Department of Physics, Faculty of Science, Chulalongkorn University,Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand); Theoretische Natuurkunde, Vrije Universiteit Brussel and The International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium); Jai-akson, Puttarak [Department of Physics, Faculty of Science, Chulalongkorn University,Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand)

    2016-04-11

    We present a range of methods suitable for accurate evaluation of the leading asymptotics for integrals of products of Jacobi polynomials in limits when the degrees of some or all polynomials inside the integral become large. The structures in question have recently emerged in the context of effective descriptions of small amplitude perturbations in anti-de Sitter (AdS) spacetime. The limit of high degree polynomials corresponds in this situation to effective interactions involving extreme short-wavelength modes, whose dynamics is crucial for the turbulent instabilities that determine the ultimate fate of small AdS perturbations. We explicitly apply the relevant asymptotic techniques to the case of a self-interacting probe scalar field in AdS and extract a detailed form of the leading large degree behavior, including closed form analytic expressions for the numerical coefficients appearing in the asymptotics.

  1. Asymptotically AdS spacetimes with a timelike Kasner singularity

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jie [Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel)

    2016-07-21

    Exact solutions to Einstein’s equations for holographic models are presented and studied. The IR geometry has a timelike cousin of the Kasner singularity, which is the less generic case of the BKL (Belinski-Khalatnikov-Lifshitz) singularity, and the UV is asymptotically AdS. This solution describes a holographic RG flow between them. The solution’s appearance is an interpolation between the planar AdS black hole and the AdS soliton. The causality constraint is always satisfied. The entanglement entropy and Wilson loops are discussed. The boundary condition for the current-current correlation function and the Laplacian in the IR is examined. There is no infalling wave in the IR, but instead, there is a normalizable solution in the IR. In a special case, a hyperscaling-violating geometry is obtained after a dimensional reduction.

  2. Asymptotically AdS spacetimes with a timelike Kasner singularity

    Science.gov (United States)

    Ren, Jie

    2016-07-01

    Exact solutions to Einstein's equations for holographic models are presented and studied. The IR geometry has a timelike cousin of the Kasner singularity, which is the less generic case of the BKL (Belinski-Khalatnikov-Lifshitz) singularity, and the UV is asymptotically AdS. This solution describes a holographic RG flow between them. The solution's appearance is an interpolation between the planar AdS black hole and the AdS soliton. The causality constraint is always satisfied. The entanglement entropy and Wilson loops are discussed. The boundary condition for the current-current correlation function and the Laplacian in the IR is examined. There is no infalling wave in the IR, but instead, there is a normalizable solution in the IR. In a special case, a hyperscaling-violating geometry is obtained after a dimensional reduction.

  3. Revisiting the thermodynamic relations in AdS /CMT models

    Science.gov (United States)

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon

    2017-03-01

    Motivated by the recent unified approach to the Smarr-like relation of anti-de Sitter (AdS) planar black holes in conjunction with the quasilocal formalism on conserved charges, we revisit the quantum statistical and thermodynamic relations of hairy AdS planar black holes. By extending the previous results, we identify the hairy contribution in the bulk and show that the holographic computation can be improved so that it is consistent with the bulk computation. We argue that the first law can be retained in its universal form and that the relation between the on-shell renormalized Euclidean action and its free energy interpretation in gravity may also be undeformed even with the hairy contribution in hairy AdS black holes.

  4. Mapping AdS to dS and back

    CERN Document Server

    Di Dato, Adriana

    2014-01-01

    We derive a map between Einstein spaces of positive and negative curvature. Starting from a space of positive curvature with some dimensions compactified on a sphere and analytically continuing the number of compact dimensions, we obtain a space of negative curvature with a compact hyperbolic subspace, and vice versa. Prime examples of such spaces are de Sitter and Anti-de Sitter space, as well as black hole spacetimes with (A)dS asymptotics and perturbed versions thereof, which play an important role in holography. This map extends work done by Caldarelli et.al., who map asymptotically AdS spaces to Ricci-flat ones. A remarkable result is that the boundary of asymptotically AdS spaces is mapped to a brane in the bulk of de Sitter, and perturbations near the AdS boundary are sourced by a stress tensor confined to this brane. We also calculate the Brown-York stress tensor for the perturbed AdS metric, which turns out to be the negative of the stress tensor on the de Sitter brane.

  5. An $xp$ model on $AdS_2$ spacetime

    OpenAIRE

    2012-01-01

    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, whose absolute values are given by a harmonic oscillator spectrum, which in turn coincides with that of a massive Dirac fermion in AdS$_2$. We extend this result to generic $xp$ models which are shown to be equivalent to a massive Dirac fermion on spacetimes whose metric depend of the $xp$ Hamiltonian. Finally, we construct the generators of t...

  6. AdS5 magnetized solutions in minimal gauged supergravity

    Directory of Open Access Journals (Sweden)

    Jose Luis Blázquez-Salcedo

    2017-08-01

    Full Text Available We construct a generalization of the AdS charged rotating black holes with two equal magnitude angular momenta in five-dimensional minimal gauged supergravity. In addition to the mass, electric charge and angular momentum, the new solutions possess an extra-parameter associated with a non-zero magnitude of the magnetic potential at infinity. In contrast with the known cases, these new black holes possess a non-trivial zero-horizon size limit which describes a one parameter family of spinning charged solitons. All configurations reported in this work approach asymptotically an AdS5 spacetime in global coordinates and are free of pathologies.

  7. Diffusion and Chaos from near AdS$_2$ horizons

    CERN Document Server

    Blake, Mike

    2016-01-01

    We calculate the thermal diffusivity $D = \\kappa/c_{\\rho}$ and butterfly velocity $v_B$ in holographic models that flow to AdS$_2 \\times R^{d}$ fixed points in the infra-red. We show that both these quantities are governed by the same irrelevant deformation of AdS$_2$ and hence establish a simple relationship between them. When this deformation corresponds to a universal dilaton mode of dimension $\\Delta = 2$ then this relationship is always given by $D = v_B^2/(2 \\pi T)$.

  8. Penrose inequality for asymptotically AdS spaces

    Energy Technology Data Exchange (ETDEWEB)

    Itkin, Igor [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel); Oz, Yaron, E-mail: yaronoz@post.tau.ac.il [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel)

    2012-02-28

    In general relativity, the Penrose inequality relates the mass and the entropy associated with a gravitational background. If the inequality is violated by an initial Cauchy data, it suggests a creation of a naked singularity, thus providing means to consider the cosmic censorship hypothesis. We propose a general form of Penrose inequality for asymptotically locally AdS spaces.

  9. Internet Advertising. Google AdWords versus Facebook Ads

    Directory of Open Access Journals (Sweden)

    Paul PAŞCU

    2014-05-01

    Full Text Available This article describes how to use the applications for Internet advertising, Google AdWords and Facebook Ads. Our attempt is to present the advantages and disadvantages of each of them, the costs and benefits, a useful aspect for companies that plan to start advertising campaigns on the Internet.

  10. Predicting AD conversion: comparison between prodromal AD guidelines and computer assisted PredictAD tool.

    Directory of Open Access Journals (Sweden)

    Yawu Liu

    Full Text Available To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA on MRI and CSF biomarkers.Altogether 391 MCI cases (158 AD converters were selected from the ADNI cohort. All the cases had baseline cognitive tests, MRI and/or CSF levels of Aβ1-42 and Tau. Using baseline data, the status of MCI patients (AD or MCI three years later was predicted using current diagnostic research guidelines and the PredictAD software tool designed for supporting clinical diagnostics. The data used were 1 clinical criteria for episodic memory loss of the hippocampal type, 2 visual MTA, 3 positive CSF markers, 4 their combinations, and 5 when the PredictAD tool was applied, automatically computed MRI measures were used instead of the visual MTA results. The accuracies of diagnosis were evaluated with the diagnosis made 3 years later.The PredictAD tool achieved the overall accuracy of 72% (sensitivity 73%, specificity 71% in predicting the AD diagnosis. The corresponding number for a clinician's prediction with the assistance of the PredictAD tool was 71% (sensitivity 75%, specificity 68%. Diagnosis with the PredictAD tool was significantly better than diagnosis by biomarkers alone or the combinations of clinical diagnosis of hippocampal pattern for the memory loss and biomarkers (p≤0.037.With the assistance of PredictAD tool, the clinician can predict AD conversion more accurately than the current diagnostic criteria.

  11. AdS5 backgrounds with 24 supersymmetries

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2016-06-01

    We prove a non-existence theorem for smooth AdS 5 solutions with connected, compact without boundary internal space that preserve strictly 24 supersymmetries. In particular, we show that D = 11 supergravity does not admit such solutions, and that all such solutions of IIB supergravity are locally isometric to the AdS 5 × S 5 maximally supersymmetric background. Furthermore, we prove that (massive) IIA supergravity also does not admit such solutions, provided that the homogeneity conjecture for massive IIA supergravity is valid. In the context of AdS/CFT these results imply that if gravitational duals for strictly mathcal{N}=3 superconformal theories in 4-dimensions exist, they are either singular or their internal spaces are not compact.

  12. Coset construction of AdS particle dynamics

    CERN Document Server

    Heinze, Martin; Megrelidze, Luka

    2016-01-01

    We analyze dynamics of the AdS$_{N+1}$ particle realized on the coset SO$(2,N)/$SO$(1,N)$. Hamiltonian reduction provides the physical phase space in terms of the coadjoint orbit obtained by boosting a timelike element of ${\\frak so}(2,N)$. We show equivalence of this approach to geometric quantization and to the SO$(N)$ covariant oscillator description, for which the boost generators entail a complicated operator ordering. As an alternative scheme, we introduce dual oscillator variables and derive their algebra at the classical and the quantum level. This simplifies the calculations of the commutators for the boost generators and leads to unitary irreducible representations of ${\\frak so}(2,N)$ for all admissible values of the mass parameter. We furthermore discuss a SO$(N)$ covariant supersymmetric extensions of the oscillator quantization, with its realization for superparticles in AdS$_2$ and AdS$_3$ given by recent works.

  13. Sub-AdS Scale Locality in AdS$_3$/CFT$_2$

    CERN Document Server

    Belin, Alexandre; Jefferson, Robert A; Kabir, Laurens

    2016-01-01

    We investigate sub-AdS scale locality in a weakly coupled toy model of the AdS$_3$/CFT$_2$ correspondence. We find that this simple model has the correct density of states at low and high energies to be dual to Einstein gravity coupled to matter in AdS$_3$. Bulk correlation functions also have the correct behavior at leading order in the large $N$ expansion, but non-local effects emerge at order $1/N$. Our analysis leads to the conjecture that any large $N$ CFT$_2$ that is modular invariant and has the right low-energy density of states is dual to a gravitational theory with sub-AdS scale locality.

  14. Ultraviolet asymptotics for quasiperiodic AdS_4 perturbations

    CERN Document Server

    Craps, Ben; Jai-akson, Puttarak; Vanhoof, Joris

    2015-01-01

    Spherically symmetric perturbations in AdS-scalar field systems of small amplitude epsilon approximately periodic on time scales of order 1/epsilon^2 (in the sense that no significant transfer of energy between the AdS normal modes occurs) have played an important role in considerations of AdS stability. They are seen as anchors of stability islands where collapse of small perturbations to black holes does not occur. (This collapse, if it happens, typically develops on time scales of the order 1/epsilon^2.) We construct an analytic treatment of the frequency spectra of such quasiperiodic perturbations, paying special attention to the large frequency asymptotics. For the case of a self-interacting phi^4 scalar field in a non-dynamical AdS background, we arrive at a fairly complete analytic picture involving quasiperiodic spectra with an exponential suppression modulated by a power law at large mode numbers. For the case of dynamical gravity, the structure of the large frequency asymptotics is more complicated....

  15. AdS nonlinear instability: moving beyond spherical symmetry

    CERN Document Server

    Dias, Oscar J C

    2016-01-01

    Anti-de Sitter (AdS) is conjectured to be nonlinear unstable to a weakly turbulent mechanism that develops a cascade towards high frequencies, leading to black hole formation [1,2]. We give evidence that the gravitational sector of perturbations behaves differently from the scalar one studied in [2]. In contrast with [2], we find that not all gravitational normal modes of AdS can be nonlinearly extended into periodic horizonless smooth solutions of the Einstein equation. In particular, we show that even seeds with a single normal mode can develop secular resonances, unlike the spherically symmetric scalar field collapse studied in [2]. Moreover, if the seed has two normal modes, more than one resonance can be generated at third order, unlike the spherical collapse of [2]. We also show that weak turbulent perturbative theory predicts the existence of direct and inverse cascades, with the former dominating the latter for equal energy two-mode seeds.

  16. Universal isolation in the AdS landscape

    Science.gov (United States)

    Danielsson, U. H.; Dibitetto, G.; Vargas, S. C.

    2016-12-01

    We study the universal conditions for quantum nonperturbative stability against bubble nucleation for pertubatively stable AdS vacua based on positive energy theorems. We also compare our analysis with the preexisting ones in the literature carried out within the thin-wall approximation. The aforementioned criterion is then tested in two explicit examples describing massive type IIA string theory compactified on S3 and S3×S3, respectively. The AdS landscape of both classes of compactifications is known to consist of a set of isolated points. The main result is that all critical points respecting the Breitenlohner-Freedman (BF) bound also turn out be stable at a nonperturbative level. Finally, we speculate on the possible universal features that may be extracted from the above specific examples.

  17. The Mixed Phase of Charged AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Piyabut Burikham

    2016-01-01

    Full Text Available We study the mixed phase of charged AdS black hole and radiation when the total energy is fixed below the threshold to produce a stable charged black hole branch. The coexistence conditions for the charged AdS black hole and radiation are derived for the generic case when radiation particles carry charge. The phase diagram of the mixed phase is demonstrated for both fixed potential and charge ensemble. In the dual gauge picture, they correspond to the mixed phase of quark-gluon plasma (QGP and hadron gas in the fixed chemical potential and density ensemble, respectively. In the nuclei and heavy-ion collisions at intermediate energies, the mixed phase of exotic QGP and hadron gas could be produced. The mixed phase will condense and evaporate into the hadron gas as the fireball expands.

  18. Smoothed Transitions in Higher Spin AdS Gravity

    CERN Document Server

    Banerjee, Shamik; Hellerman, Simeon; Hijano, Eliot; Lepage-Jutier, Arnaud; Maloney, Alexander; Shenker, Stephen

    2012-01-01

    We consider CFTs conjectured to be dual to higher spin theories of gravity in AdS_3 and AdS_4. Two dimensional CFTs with W_N symmetry are considered in the lambda=0 (k --> infinity) limit, where they are conjectured to be described by continuous orbifolds. The torus partition function is computed, using reasonable assumptions, and equals that of a free field theory. We find no phase transition at temperatures of order one; the usual Hawking-Page phase transition is removed by the highly degenerate light states associated with conical defect states in the bulk. Three dimensional Chern-Simons-matter CFTs with vector-like matter are considered on T^3, where the dynamics is described by an effective theory for the eigenvalues of the holonomies. Likewise, we find no evidence for a Hawking-Page phase transition at large level k.

  19. Perturbative entanglement thermodynamics for AdS spacetime: Renormalization

    CERN Document Server

    Mishra, Rohit

    2015-01-01

    We study the effect of charged excitations in the AdS spacetime on the first law of entanglement thermodynamics. It is found that `boosted' AdS black holes give rise to a more general form of first law which includes chemical potential and charge density. To obtain this result we have to resort to a second order perturbative calculation of entanglement entropy for small size subsystems. At first order the form of entanglement law remains unchanged even in the presence of charged excitations. But the thermodynamic quantities have to be appropriately `renormalized' at the second order due to the corrections. We work in the perturbative regime where $T_{thermal}\\ll T_E$.

  20. Thermodynamics of Einstein-Proca AdS Black Holes

    CERN Document Server

    Liu, Hai-Shan; Pope, C N

    2014-01-01

    We study static spherically-symmetric solutions of the Einstein-Proca equations in the presence of a negative cosmological constant. We show that the theory admits solutions describing both black holes and also solitons in an asymptotically AdS background. Interesting subtleties can arise in the computation of the mass of the solutions and also in the derivation of the first law of thermodynamics. We make use of holographic renormalisation in order to calculate the mass, even in cases where the solutions have a rather slow approach to the asymptotic AdS geometry. By using the procedure developed by Wald, we derive the first law of thermodynamics for the black hole and soliton solutions. This includes a non-trivial contribution associated with the Proca "charge." The solutions cannot be found analytically, and so we make use of numerical integration techniques to demonstrate their existence.

  1. Note on classical string dynamics on AdS3

    Science.gov (United States)

    Bañados, Máximo; Ritz, Adam

    1999-12-01

    We consider bosonic strings propagating on Euclidean anti-de Sitter space (AdS3), and study in particular the realization of various worldsheet symmetries. We give a proper definition for the Brown-Henneaux asymptotic target space symmetry, when acting on the string action, and derive the Giveon-Kutasov-Seiberg worldsheet contour integral representation simply by using Noether's theorem. We show that making identifications in the target space is equivalent to the insertion of an (exponentiated) graviton vertex operator carrying the corresponding charge. Finally, we point out an interesting relation between 3D gravity and the dynamics of the worldsheet on AdS3. Both theories are described by an SL(2,C)/SU(2) Wess-Zumino-Witten (WZW) model, and we prove that the reduction conditions determined on one hand by worldsheet diffeomorphism invariance, and on the other by the Brown-Henneaux boundary conditions, are the same.

  2. Observing quantum gravity in asymptotically AdS space

    Science.gov (United States)

    Emelyanov, Slava

    2015-12-01

    The question is studied of whether an observer can discover quantum gravity in the semiclassical regime. It is shown that it is indeed possible to probe a certain quantum gravity effect by employing an appropriately designed detector. The effect is related to the possibility of having topologically inequivalent geometries in the path-integral approach at the same time. A conformal field theory (CFT) state which is expected to describe the eternal anti-de Sitter (AdS) black hole in the large-N limit is discussed. It is argued under certain assumptions that the black hole boundary should be merely a patch of the entire AdS boundary. This leads then to a conclusion that that CFT state is the ordinary CFT vacuum restricted to that patch. If existent, the bulk CFT operators can behave as the ordinary semiclassical quantum field theory in the large-N limit in the weak sense.

  3. Semiclassical Virasoro Blocks from AdS$_3$ Gravity

    CERN Document Server

    Hijano, Eliot; Perlmutter, Eric; Snively, River

    2015-01-01

    We present a unified framework for the holographic computation of Virasoro conformal blocks at large central charge. In particular, we provide bulk constructions that correctly reproduce all semiclassical Virasoro blocks that are known explicitly from conformal field theory computations. The results revolve around the use of geodesic Witten diagrams, recently introduced in arXiv:1508.00501, evaluated in locally AdS$_3$ geometries generated by backreaction of heavy operators. We also provide an alternative computation of the heavy-light semiclassical block -- in which two external operators become parametrically heavy -- as a certain scattering process involving higher spin gauge fields in AdS$_3$; this approach highlights the chiral nature of Virasoro blocks. These techniques may be systematically extended to compute corrections to these blocks and to interpolate amongst the different semiclassical regimes.

  4. AdS plane waves, entanglement and mutual information

    CERN Document Server

    Mukherjee, Debangshu

    2014-01-01

    $AdS$ plane wave backgrounds are dual to CFT excited states with energy momentum density $T_{++}=Q$. Building on previous work on entanglement entropy in these and nonconformal brane plane wave backgrounds, we first describe a phenomenological scaling picture for entanglement in terms of "entangling partons". We then study aspects of holographic mutual information in these backgrounds for two strip shaped subsystems, aligned parallel or orthogonal to the flux. We focus on the wide ($Ql^d\\gg 1$) and narrow ($Ql^d\\ll 1$) strip regimes. In the wide strip regime, mutual information exhibits growth with the individual strip sizes and a disentangling transition as the separation between the strips increases, whose behaviour is distinct from the ground and thermal states. In the narrow strip case, our calculations have parallels with "entanglement thermodynamics" for these $AdS$ plane wave deformations. We also discuss some numerical analysis.

  5. N=2 supersymmetric sigma-models in AdS

    CERN Document Server

    Butter, Daniel

    2011-01-01

    We construct the most general N=2 supersymmetric nonlinear sigma-model in four-dimensional anti-de Sitter (AdS) space in terms of N=1 chiral superfields. The target space is shown to be a non-compact hyperkahler manifold restricted to possess a special Killing vector field. A remarkable property of the sigma-model constructed is that the algebra of OSp(2|4) transformations is closed off the mass shell.

  6. Generalised structures for N=1 AdS backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Coimbra, André [Institut für Theoretische Physik & Center for Quantum Engineering and Spacetime Research,Leibniz Universität Hannover,Appelstraße 2, 30167 Hannover (Germany); Strickland-Constable, Charles [Institut de physique théorique, Université Paris Saclay, CEA, CNRS, Orme des Merisiers, F-91191 Gif-sur-Yvette (France)

    2016-11-16

    We expand upon a claim made in a recent paper [http://arxiv.org/abs/1411.5721] that generic minimally supersymmetric AdS backgrounds of warped flux compactifications of Type II and M theory can be understood as satisfying a straightforward weak integrability condition in the language of E{sub d(d)}×ℝ{sup +} generalised geometry. Namely, they are spaces admitting a generalised G-structure set by the Killing spinor and with constant singlet generalised intrinsic torsion.

  7. SUSY properties of warped AdS3

    Science.gov (United States)

    Jeong, Jaehoon; Colgáin, Eoin Ó.; Yoshida, Kentaroh

    2014-06-01

    We examine supersymmetric properties of null-warped AdS3, or alternatively Schrödinger geometries, dual to putative warped CFTs in two dimensions. We classify super Schrödinger subalgebras of the superalgebra psu(1, 1|2) ⊕ psu(1, 1|2), corresponding to the superconformal algebra of the AdS3 × S3 geometry. We comment on geometric realisations and provide a string theory description with enhanced supersymmetry in terms of intersecting D3-branes. For type IIB supergravity solutions based on T 1,1, we consider the relationship between five-dimensional Schrödinger solutions and their three-dimensional null-warped counterparts, corresponding to R symmetry twists. Finally, we study a family of null-warped AdS3 solutions in a setting where there is an ambiguity over the R symmetry and confirm that, for examples admitting a Kaluza-Klein (KK) reduction to three dimensions, the minimisation of a real superpotential of the three-dimensional gauged supergravity captures the central charge and R symmetry.

  8. N=2 AdS supergravity and supercurrents

    CERN Document Server

    Butter, Daniel

    2011-01-01

    We consider the minimal off-shell formulation for four-dimensional N=2 supergravity with a cosmological term, in which the second compensator is an improved tensor multiplet. We use it to derive a linearized supergravity action (and its dual versions) around the anti-de Sitter (AdS) background in terms of three N=2 off-shell multiplets: an unconstrained scalar superfield, vector and tensor multiplets. This allows us to deduce the structure of the supercurrent multiplet associated with those supersymmetric theories which naturally couple to the supergravity formulation chosen, with or without a cosmological term. Finally, our linearized N=2 AdS supergravity action is reduced to N=1 superspace. The result is a sum of two N=1 linearized actions describing (i) old minimal supergravity; and (ii) an off-shell massless gravitino multiplet. We also derive dual formulations for the massless N=1 gravitino multiplet in AdS. As a by-product of our consideration, we derive the consistent supergravity extension of the N=1 ...

  9. Intellectual mobile Ad Hoc networks

    OpenAIRE

    Sova, Oleg; Romanjuk, Valeriy; Bunin, Sergey; Zhuk, Pavlo

    2012-01-01

    In this article intellectualization of Mobile Ad Hoc Networks resources management is offered. It was proposed decomposition of the primary goal of MANET functioning into easy subgoals, and fragment of the MANET node target structure is presented.

  10. Supergravity one-loop corrections on AdS7 and AdS3, higher spins and AdS/CFT

    Directory of Open Access Journals (Sweden)

    Matteo Beccaria

    2015-03-01

    Full Text Available As was shown earlier, the one-loop correction in 10d supergravity on AdS5×S5 corresponds to the contributions to the vacuum energy and 4d boundary conformal anomaly which are minus the values for one N=4 Maxwell supermultiplet, thus reproducing the subleading term in the N2−1 coefficient in the dual SU(N SYM theory. We perform similar one-loop computations in 11d supergravity on AdS7×S4 and 10d supergravity on AdS3×S3×T4. In the AdS7 case we find that the corrections to the 6d conformal anomaly a-coefficient and the vacuum energy are again minus the ones for one (2,0 tensor multiplet, suggesting that the total a-anomaly coefficient for the dual (2,0 theory is 4N3−9/4N−7/4 and thus vanishes for N=1. In the AdS3 case the one-loop correction to the vacuum energy or 2d central charge turns out to be equal to that of one free (4,4 scalar multiplet, i.e. is c=+6. This reproduces the subleading term in the central charge c=6(Q1Q5+1 of the dual 2d CFT describing decoupling limit of D5–D1 system. We also present the expressions for the 6d a-anomaly coefficient and vacuum energy contributions of general-symmetry higher spin field in AdS7 and consider their application to tests of vectorial AdS/CFT with the boundary conformal 6d theory represented by free scalars, spinors or rank-2 antisymmetric tensors.

  11. Entanglement Temperature and Perturbed AdS$_3$ Geometry

    CERN Document Server

    Levine, Gregory

    2015-01-01

    In analogy to the first law of thermodynamics, the increase in entanglement entropy $\\delta S$ of a conformal field theory (CFT) is proportional to the increase in energy, $\\delta E$, of the subsystem divided by an effective entanglement temperature, $T_E$. Extending this analogy, we study entanglement entropy when the subsystem is perturbed by applying an external field, expressed as a coupling to a local marginal operator in the CFT. We show that the resulting entropy change is associated with a change in the entanglement temperature itself, leading to an equation analogous to the Clausius relation. Using AdS/CFT duality we develop a relationship between a perturbation in the local entanglement temperature, $\\delta T_E(x)$ of the CFT and the perturbation of the bulk AdS metric. Using the AdS$_3$ minimal surface as a probe, we can construct bulk metric perturbations from an exact numerical computation of the entanglement temperature in a two dimensional $c=1$ boundary theory deformed by a marginal perturbati...

  12. Ultraviolet asymptotics and singular dynamics of AdS perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Craps, Ben [Theoretische Natuurkunde, Vrije Universiteit Brussel, and The International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium); Evnin, Oleg [Department of Physics, Faculty of Science, Chulalongkorn University, Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand); Theoretische Natuurkunde, Vrije Universiteit Brussel, and The International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium); Vanhoof, Joris [Theoretische Natuurkunde, Vrije Universiteit Brussel, and The International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium)

    2015-10-12

    Important insights into the dynamics of spherically symmetric AdS-scalar field perturbations can be obtained by considering a simplified time-averaged theory accurately describing perturbations of amplitude ε on time-scales of order 1/ε{sup 2}. The coefficients of the time-averaged equations are complicated expressions in terms of the AdS scalar field mode functions, which are in turn related to the Jacobi polynomials. We analyze the behavior of these coefficients for high frequency modes. The resulting asymptotics can be useful for understanding the properties of the finite-time singularity in solutions of the time-averaged theory recently reported in the literature. We highlight, in particular, the gauge dependence of this asymptotics, with respect to the two most commonly used gauges. The harsher growth of the coefficients at large frequencies in higher-dimensional AdS suggests strengthening of turbulent instabilities in higher dimensions. In the course of our derivations, we arrive at recursive relations for the coefficients of the time-averaged theory that are likely to be useful for evaluating them more efficiently in numerical simulations.

  13. 'Reverse discordance' between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan: the plausible explanations and its implications for high-dose therapy with radiolabeled somatostatin receptor analogs.

    Science.gov (United States)

    Basu, Sandip; Abhyankar, Amit; Kand, Purushottam; Kumar, Rakesh; Asopa, Ramesh; Rajan, Mysore Govinda Ramakrishna; Nayak, Uday; Shimpi, Hemant; Das, Tapas; Venkatesh, Meera; Chakrabarty, Sudipta; Banerjee, Sharmila

    2011-07-01

    In this technical note, an unusual discordance between diagnostic and posttherapeutic scan resulting from the use of different somatostatin receptor ligands in two settings is described. Such observation, we believe, is multifactorial, but most importantly arises due to different receptor affinity profile of the ligands and different somatostatin receptor subtype expression in different tumors. It is important for the treating physician to be aware of this phenomenon that would aid in improving our understanding of complex ligand-receptor interactions in various somatostatin receptor-positive tumors with its possible implications for therapeutic decision making with radiolabeled somatostatin receptor analogues.

  14. Coherent Cascade: Collapsing Solutions in Global AdS

    CERN Document Server

    Freivogel, Ben

    2015-01-01

    We analyze the gravitational dynamics of a classical scalar field that sometimes leads to blackhole formation in asymptotically AdS spacetime at the shortest nonlinear time scale. We present strong evidence that the dynamics is governed by a "coherent cascade", with all modes remaining in phase as the energy flows to higher frequencies into a power-law spectrum. Using a coherent phase ansatz, we analytically find these power-law solutions. We show how the particular power is determined by the scaling properties of the interaction coefficients. Our result agrees with existing numerical results in 4+1 dimensions, and makes predictions in higher dimensions.

  15. Configurational entropy of charged AdS black holes

    Science.gov (United States)

    Lee, Chong Oh

    2017-09-01

    When we consider charged AdS black holes in higher dimensional spacetime and a molecule number density along coexistence curves is numerically extended to higher dimensional cases. It is found that a number density difference of a small and large black holes decrease as a total dimension grows up. In particular, we find that a configurational entropy is a concave function of a reduced temperature and reaches a maximum value at a critical (second-order phase transition) point. Furthermore, the bigger a total dimension becomes, the more concave function in a configurational entropy while the more convex function in a reduced pressure.

  16. Internal Structure of Charged AdS Black Holes

    CERN Document Server

    Bhattacharjee, Srijit; Virmani, Amitabh

    2016-01-01

    When an electrically charged black hole is perturbed its inner horizon becomes a singularity, often referred to as the Poisson-Israel mass inflation singularity. Ori constructed a model of this phenomenon for asymptotically flat black holes, in which the metric can be determined explicitly in the mass inflation region. In this paper we implement the Ori model for charged AdS black holes. We find that the mass function inflates faster than the flat space case as the inner horizon is approached. Nevertheless, the mass inflation singularity is still a weak singularity: although spacetime curvature becomes infinite, tidal distortions remain finite on physical objects attempting to cross it.

  17. Duality invariance of s≥32 fermions in AdS

    Directory of Open Access Journals (Sweden)

    S. Deser

    2014-11-01

    Full Text Available We show that in D=4 AdS, s≥3/2 partially massless (PM fermions retain the duality invariances of their flat space massless counterparts. They have tuned ratios m2/M2≠0 that turn them into sums of effectively massless unconstrained helicity ±(s,⋯,32 excitations, shorn of the lowest (non-dual helicity ±12-rung and — more generally — of succeeding higher rung as well. Each helicity mode is separately duality invariant, like its flat space counterpart.

  18. Reentrant Phase Transitions in Rotating AdS Black Holes

    CERN Document Server

    Altamirano, Natacha; Mann, Robert B

    2013-01-01

    We study the thermodynamics of higher-dimensional singly spinning asymptotically AdS black holes in the canonical (fixed J) ensemble of extended phase space, where the cosmological constant is treated as pressure and the corresponding conjugate quantity is interpreted as thermodynamic volume. Along with the usual small/large black hole phase transition, we find a new phenomenon of reentrant phase transitions for all d>5 dimensions, in which a monotonic variation of the temperature yields two phase transitions from large to small and back to large black holes. This situation is similar to that seen in multicomponent liquids.

  19. Entanglement entropy and duality in AdS4

    Directory of Open Access Journals (Sweden)

    Ioannis Bakas

    2015-07-01

    Full Text Available Small variations of the entanglement entropy δS and the expectation value of the modular Hamiltonian δE are computed holographically for circular entangling curves in the boundary of AdS4, using gravitational perturbations with general boundary conditions in spherical coordinates. Agreement with the first law of thermodynamics, δS=δE, requires that the line element of the entangling curve remains constant. In this context, we also find a manifestation of electric–magnetic duality for the entanglement entropy and the corresponding modular Hamiltonian, following from the holographic energy–momentum/Cotton tensor duality.

  20. Most general AdS_3 boundary conditions

    CERN Document Server

    Grumiller, Daniel

    2016-01-01

    We consider the most general asymptotically anti-de Sitter boundary conditions in three-dimensional Einstein gravity with negative cosmological constant. The metric contains in total twelve independent functions, six of which are interpreted as chemical potentials (or non-normalizable fluctuations) and the other half as canonical boundary charges (or normalizable fluctuations). Their presence modifies the usual Fefferman-Graham expansion. The asymptotic symmetry algebra consists of two sl(2)_k current algebras, the levels of which are given by k=l/(4G_N), where l is the AdS radius and G_N the three-dimensional Newton constant.

  1. M-Theory solutions with AdS factors

    CERN Document Server

    Gauntlett, J P; Pakis, S; Waldram, D; Gauntlett, Jerome P.; Kim, Nakwoo; Pakis, Stathis; Waldram, Daniel

    2002-01-01

    Solutions of D=7 maximal gauged supergravity are constructed with metrics that are a product of a n-dimensional anti-de Sitter (AdS) space, with n=2,3,4,5, and certain Einstein manifolds. The gauge fields have the same form as in the recently constructed solutions describing the near-horizon limits of M5-branes wrapping supersymmetric cycles. The new solutions do not preserve any supersymmetry and can be uplifted to obtain new solutions of D=11 supergravity, which are warped and twisted products of the D=7 metric with a squashed four-sphere. Some aspects of the stability of the solutions are discussed.

  2. M-theory solutions with AdS factors

    Energy Technology Data Exchange (ETDEWEB)

    Gauntlett, Jerome P [Department of Physics, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom); Kim, Nakwoo [Max-Planck-Institut fuer Gravitationsphysik, Albert-Einstein-Institut, Am Muehlenberg 1, D-14476 Golm (Germany); Pakis, Stathis [Department of Physics, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom); Waldram, Daniel [Department of Physics, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom)

    2002-08-07

    Solutions of D=7 maximal gauged supergravity are constructed with metrics that are a product of an n-dimensional anti-de Sitter (AdS) space, with n=2, 3, 4, 5, and certain Einstein manifolds. The gauge fields have the same form as in the recently constructed solutions describing the near-horizon limits of M5-branes wrapping supersymmetric cycles. The new solutions do not preserve any supersymmetry and can be uplifted to obtain new solutions of D=11 supergravity, which are warped and twisted products of the D=7 metric with a squashed four-sphere. Some aspects of the stability of the solutions are discussed.

  3. Heavy quark potential from deformed AdS5 models

    Science.gov (United States)

    Zhang, Zi-qiang; Hou, De-fu; Chen, Gang

    2017-04-01

    In this paper, we investigate the heavy quark potential in some holographic QCD models. The calculation relies on a modified renormalization scheme mentioned in a previous work of Albacete et al. After studying the heavy quark potential in Pirner-Galow model and Andreev-Zakharov model, we extend the discussion to a general deformed AdS5 case. It is shown that the obtained potential is negative definite for all quark-antiquark separations, differs from that using the usual renormalization scheme.

  4. AdS Chern-Simons Gravity induces Conformal Gravity

    CERN Document Server

    Aros, Rodrigo

    2013-01-01

    The leitmotif of this paper is the question of whether four- and higher even-dimensional Conformal Gravities do have a Chern-Simons pedigree. We show that Weyl gravity can be obtained as dimensional reduction of a five-dimensional Chern-Simons action for a suitable (gauged-fixed, tractor-like) five-dimensional AdS connection. The gauge-fixing and dimensional reduction program admits a readily generalization to higher dimensions for the case of certain conformal gravities obtained by contractions of the Weyl tensor.

  5. Methods for chemical recovery of non-carrier-added radioactive tin from irradiated intermetallic Ti-Sb targets

    Science.gov (United States)

    Lapshina, Elena V [Troitsk, RU; Zhuikov, Boris L [Troitsk, RU; Srivastava, Suresh C [Setauket, NY; Ermolaev, Stanislav V [Obninsk, RU; Togaeva, Natalia R [Obninsk, RU

    2012-01-17

    The invention provides a method of chemical recovery of no-carrier-added radioactive tin (NCA radiotin) from intermetallide TiSb irradiated with accelerated charged particles. An irradiated sample of TiSb can be dissolved in acidic solutions. Antimony can be removed from the solution by extraction with dibutyl ether. Titanium in the form of peroxide can be separated from tin using chromatography on strong anion-exchange resin. In another embodiment NCA radiotin can be separated from iodide solution containing titanium by extraction with benzene, toluene or chloroform. NCA radiotin can be finally purified from the remaining antimony and other impurities using chromatography on silica gel. NCA tin-117m can be obtained from this process. NCA tin-117m can be used for labeling organic compounds and biological objects to be applied in medicine for imaging and therapy of various diseases.

  6. Introducing ADS 2.0

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Luker, J.; Chyla, R.; Murray, S. S.

    2014-01-01

    In the spring of 1993, the Smithsonian/NASA Astrophysics Data System (ADS) first launched its bibliographic search system. It was known then as the ADS Abstract Service, a component of the larger Astrophysics Data System effort which had developed an interoperable data system now seen as a precursor of the Virtual Observatory. As a result of the massive technological and sociological changes in the field of scholarly communication, the ADS is now completing the most ambitious technological upgrade in its twenty-year history. Code-named ADS 2.0, the new system features: an IT platform built on web and digital library standards; a new, extensible, industrial strength search engine; a public API with various access control capabilities; a set of applications supporting search, export, visualization, analysis; a collaborative, open source development model; and enhanced indexing of content which includes the full-text of astronomy and physics publications. The changes in the ADS platform affect all aspects of the system and its operations, including: the process through which data and metadata are harvested, curated and indexed; the interface and paradigm used for searching the database; and the follow-up analysis capabilities available to the users. This poster describes the choices behind the technical overhaul of the system, the technology stack used, and the opportunities which the upgrade is providing us with, namely gains in productivity and enhancements in our system capabilities.

  7. Rindler-AdS/CFT

    CERN Document Server

    Parikh, Maulik

    2012-01-01

    In anti-de Sitter space a highly accelerating observer perceives a Rindler horizon. The two Rindler wedges in AdS_{d+1} are holographically dual to an entangled conformal field theory that lives on two boundaries with geometry R x H_{d-1}. For AdS_3, the holographic duality is especially tractable, allowing quantum-gravitational aspects of Rindler horizons to be probed. We recover the thermodynamics of Rindler-AdS space directly from the boundary conformal field theory. We derive the temperature from the two-point function and obtain the Rindler entropy density precisely, including numerical factors, using the Cardy formula. We also probe the causal structure of the spacetime, and find from the behavior of the one-point function that the CFT "knows" when a source has fallen across the Rindler horizon. This is so even though, from the bulk point of view, there are no local signifiers of the presence of the horizon. Finally, we discuss an alternate foliation of Rindler-AdS which is dual to a CFT living in de Si...

  8. The CFT dual of AdS gravity with torsion

    CERN Document Server

    Klemm, Dietmar

    2007-01-01

    We consider the Mielke-Baekler model of three-dimensional AdS gravity with torsion, which has gravitational and translational Chern-Simons terms in addition to the usual Einstein-Hilbert action with cosmological constant. It is shown that the topological nature of the model leads to a finite Fefferman-Graham expansion. We derive the holographic stress tensor and the associated Ward identities and show that, due to the asymmetry of the left- and right-moving central charges, a Lorentz anomaly appears in the dual conformal field theory. Both the consistent and the covariant Weyl and Lorentz anomaly are determined, and the Wess-Zumino consistency conditions for the former are verified. Moreover we consider the most general solution with flat boundary geometry, which describes left-and right-moving gravitational waves on AdS_3 with torsion, and shew that in this case the holographic energy-momentum tensor is given by the wave profiles. The anomalous transformation laws of the wave profiles under diffeomorphisms p...

  9. AdS nonlinear instability: moving beyond spherical symmetry

    Science.gov (United States)

    Dias, Óscar J. C.; Santos, Jorge E.

    2016-12-01

    Anti-de Sitter (AdS) is conjectured to be nonlinear unstable to a weakly turbulent mechanism that develops a cascade towards high frequencies, leading to black hole formation (Dafermos and Holzegel 2006 Seminar at DAMTP (University of Cambridge) available at https://dpmms.cam.ac.uk/~md384/ADSinstability.pdf, Bizon and Rostworowski 2011 Phys. Rev. Lett. 107 031102). We give evidence that the gravitational sector of perturbations behaves differently from the scalar one studied by Bizon and Rostworowski. In contrast with Bizon and Rostworowski, we find that not all gravitational normal modes of AdS can be nonlinearly extended into periodic horizonless smooth solutions of the Einstein equation. In particular, we show that even seeds with a single normal mode can develop secular resonances, unlike the spherically symmetric scalar field collapse studied by Bizon and Rostworowski. Moreover, if the seed has two normal modes, more than one resonance can be generated at third order, unlike the spherical collapse of Bizon and Rostworowski. We also show that weak turbulent perturbative theory predicts the existence of direct and inverse cascades, with the former dominating the latter for equal energy two-mode seeds.

  10. AdS pure spinor superstring in constant backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Chandia, Osvaldo [Departamento de Ciencias, Facultad de Artes Liberales, Universidad Adolfo Ibáñez,Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez,Diagonal Las Torres 2640, Peñalolén, Santiago (Chile); Bevilaqua, L. Ibiapina [Escola de Ciências e Tecnologia, Universidade Federal do Rio Grande do Norte,Caixa Postal 1524, 59072-970, Natal, RN (Brazil); Vallilo, Brenno Carlini [Facultad de Ciencias Exactas, Departamento de Ciencias Físicas, Universidad Andres Bello,Republica 220, Santiago (Chile)

    2014-06-05

    In this paper we study the pure spinor formulation of the superstring in AdS{sub 5}×S{sup 5} around point particle solutions of the classical equations of motion. As a particular example we quantize the pure spinor string in the BMN background.

  11. A special road to AdS vacua

    CERN Document Server

    Cassani, Davide; Marrani, Alessio; Morales, Jose F; Samtleben, Henning

    2010-01-01

    We apply the techniques of special Kaehler geometry to investigate AdS_4 vacua of general N=2 gauged supergravities underlying flux compactifications of type II theories. We formulate the scalar potential and its extremization conditions in terms of a triplet of prepotentials P_x and their special Kaehler covariant derivatives only, in a form that recalls the potential and the attractor equations of N=2 black holes. We propose a system of first order equations for the P_x which generalize the supersymmetry conditions and yield non-supersymmetric vacua. Special geometry allows us to recast these equations in algebraic form, and we find an infinite class of new N=0 and N=1 AdS_4 solutions, displaying a rich pattern of non-trivial charges associated with NSNS and RR fluxes. Finally, by explicit evaluation of the entropy function on the solutions, we derive a U-duality invariant expression for the cosmological constant and the central charges of the dual CFT's.

  12. AdS twistors for higher spin theory

    CERN Document Server

    Cederwall, M

    2004-01-01

    We construct spectra of supersymmetric higher spin theories in D=4, 5 and 7 from twistors describing massless (super-)particles on AdS spaces. A massless twistor transform is derived in a geometric way from classical kinematics. Relaxing the spin-shell constraints on twistor space gives an infinite tower of massless states of a ``higher spin particle'', generalising previous work of Bandos et al. This can generically be done in a number of ways, each defining the states of a distinct higher spin theory, and the method provides a systematic way of finding these. We reproduce known results in D=4, minimal supersymmetric 5- and 7-dimensional models, as well as supersymmetrisations of Vasiliev's Sp-models as special cases. In the latter models a dimensional enhancement takes place, meaning that the theory lives on a space of higher dimension than the original AdS space, and becomes a theory of doubletons. This talk was presented at the XIXth Max Born Symposium ``Fundamental Interactions and Twistor-Like Methods''...

  13. Enthalpy and the Mechanics of AdS Black Holes

    CERN Document Server

    Kastor, David; Traschen, Jennie

    2009-01-01

    We present geometric derivations of the Smarr formula for static AdS black holes and an expanded first law that includes variations in the cosmological constant. These two results are further related by a scaling argument based on Euler's theorem. The key new ingredient in the constructions is a two-form potential for the static Killing field. Surface integrals of the Killing potential determine the coefficient of the variation of the cosmological constant in the first law. This coefficient is proportional to a finite, effective volume for the region outside the AdS black hole horizon, which can also be interpreted as minus the volume excluded from a spatial slice by the black hole horizon. This effective volume also contributes to the Smarr formula. Since the cosmological constant is naturally thought of as a pressure, the new term in the first law has the form of effective volume times change in pressure that arises in the variation of the enthalpy in classical thermodynamics. This and related arguments sug...

  14. Quantum cat map dynamics on AdS$_2$

    CERN Document Server

    Axenides, Minos; Nicolis, Stam

    2016-01-01

    We present a toy model for the chaotic unitary scattering of single particle wave packets on the radial AdS$_2$ geometry of extremal BH horizons. Based on our recent work for the discretization of the AdS$_2$ space-time, which describes a finite and random geometry, by modular arithmetic, we investigate the validity of the eigenstate thermalization hypothesis (ETH), as well as that of the fast scrambling time bound conjecture (STB), for an observer with time evolution operator the quantum Arnol'd cat map (QACM). We find that the QACM, while possessing a linear spectrum, has eigenstates, which can be expressed in closed form, are found to be random and to satisfy the assumptions of the ETH.The implications are that the dynamics is described by a chaotic, unitary, single particle S-matrix, which completely delocalizes and randomizes initial gaussian wave packets . Applying results obtained by Dyson and Falk for the periods of the Arnol'd Cat Map(ACM),which are related to its mixing time, we also find that the t...

  15. Smooth Causal Patches for AdS Black Holes

    CERN Document Server

    Raju, Suvrat

    2016-01-01

    We review the paradox of low energy excitations about an AdS black hole. An appropriately chosen unitary operator in the boundary theory can create a locally strong excitation near the black hole horizon, whose global energy is small as a result of the gravitational redshift. The paradox is that this seems to violate a general rule of statistical mechanics, which states that an operator with energy parametrically smaller than $k T$ cannot create a significant excitation in a thermal system. When we carefully examine the position dependence of the boundary unitary operator that produces the excitation and the bulk observable necessary to detect the anomalously large effect, we find that they do not both fit in a single causal patch. This follows from a remarkable property of position space AdS correlators that we establish explicitly, and resolves the paradox in a generic state of the system, since no combination of observers can both create the excitation and observe its effect. As a special case of our analy...

  16. AdCell: Ad Allocation in Cellular Networks

    CERN Document Server

    Alaei, Saeed; Liaghat, Vahid; Pei, Dan; Saha, Barna

    2011-01-01

    With more than four billion usage of cellular phones worldwide, mobile advertising has become an attractive alternative to online advertisements. In this paper, we propose a new targeted advertising policy for Wireless Service Providers (WSPs) via SMS or MMS- namely {\\em AdCell}. In our model, a WSP charges the advertisers for showing their ads. Each advertiser has a valuation for specific types of customers in various times and locations and has a limit on the maximum available budget. Each query is in the form of time and location and is associated with one individual customer. In order to achieve a non-intrusive delivery, only a limited number of ads can be sent to each customer. Recently, new services have been introduced that offer location-based advertising over cellular network that fit in our model (e.g., ShopAlerts by AT&T) . We consider both online and offline version of the AdCell problem and develop approximation algorithms with constant competitive ratio. For the online version, we assume tha...

  17. Online Ad Slotting With Cancellations

    CERN Document Server

    Constantin, Florin; Muthukrishnan, S; Pal, Martin

    2008-01-01

    Many advertisers buy advertisements (ads) on the Internet or on traditional media and seek simple, online mechanisms to reserve ad slots in advance. Media publishers represent a vast and varying inventory, and they too seek automatic, online mechanisms for pricing and allocating such reservations. In this paper, we present and study a simple model for auctioning such ad slots in advance. Bidders arrive sequentially and report which slots they are interested in. The seller must decide immediately whether or not to grant a reservation. Our model allows a seller to accept reservations, but possibly cancel the allocations later and pay the bidder a cancellation compensation (bump payment). Our main result is an online mechanism to derive prices and bump payments that is efficient to implement. This mechanism has many desirable properties. It is individually rational; winners have an incentive to be honest and bidding one's true value dominates any lower bid. Our mechanism's efficiency is within a constant fractio...

  18. Adding momentum to supersymmetric geometries

    Energy Technology Data Exchange (ETDEWEB)

    Lunin, Oleg, E-mail: olunin@albany.edu [Department of Physics, University at Albany (SUNY), Albany, NY 12222 (United States); Mathur, Samir D., E-mail: mathur.16@osu.edu [Department of Physics, Ohio State University, Columbus, OH 43210 (United States); Turton, David, E-mail: turton.7@osu.edu [Department of Physics, Ohio State University, Columbus, OH 43210 (United States)

    2013-03-11

    We consider general supersymmetric solutions to minimal supergravity in six dimensions, trivially lifted to IIB supergravity. To any such solution we add a traveling wave deformation involving the additional directions. The deformed solution is given in terms of a function which is harmonic in the background geometry. We also present a family of explicit examples describing microstates of the D1-D5 system on T{sup 4}. In the case where the background contains a large AdS region, the deformation is identified as corresponding to an action of a U(1) current of the D1-D5 orbifold CFT on a given state.

  19. Adding momentum to supersymmetric geometries

    CERN Document Server

    Lunin, Oleg; Turton, David

    2012-01-01

    We consider general supersymmetric solutions to minimal supergravity in six dimensions, trivially lifted to IIB supergravity. To any such solution we add a travelling-wave deformation involving the additional directions. The deformed solution is given in terms of a function which is harmonic in the background geometry. We also present a family of explicit examples describing microstates of the D1-D5 system on T^4. In the case where the background contains a large AdS region, the deformation is identified as corresponding to an action of a U(1) current of the D1-D5 orbifold CFT on a given state.

  20. Ad valorem versus unit taxes

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Sørensen, Allan

    2010-01-01

    a general equilibrium monopolistic competition model with heterogeneous firms and intra-industry reallocations. We show that the welfare superiority of ad valorem over unit taxes under imperfect competition is not only preserved but amplified. The additional difference between the tools arises because unit...

  1. Added Value via SPI supplement

    Science.gov (United States)

    Supplement that indicates where to find the source data sets on the EPA system.This dataset is associated with the following publication:Bowden, J., K.D. Talgo, T. Spero , and C. Nolte. Assessing the Added Value of Dynamical Downscaling Using the Standardized Precipitation Index. ADVANCES IN METEOROLOGY. Hindawi Publishing Corporation, New York, NY, USA, 2016(8432064): 14 pages, (2016).

  2. Holographic properties in three-dimensional AdS soliton using $AdS_3/CFT_2$

    CERN Document Server

    Peng, Yan

    2016-01-01

    We study the holographic description of a superconductor by the $AdS_{3}/CFT_{2}$ correspondence. The system is constructed with a Maxwell field and a charged scalar field coupled in the (2+1)-dimensional AdS soliton background. With analytical methods, we obtain the exact expression for the critical chemical potential as $\\mu_{c} = 1 + \\sqrt{1+m^2}$, which has also been generalized to higher dimensions as $\\mu_c \\thickapprox a + \\sqrt{m^2-m_{BF}^2}$ in this work. Around the phase transition points, we find a correspondence between the value of the scalar field at the tip and the scalar operator at infinity. We also arrive at the classical second order phase transition threshold exponent $\\beta=\\frac{1}{2}$ as the same as the mean field theory near the critical chemical potential. As the condensation becomes heavier, we show surprisingly that superconducting phases exist only in a certain range of the chemical potential, which is very different from higher-dimensional cases. And for the small enough negative ...

  3. Brownian motion in AdS/CFT

    NARCIS (Netherlands)

    de Boer, J.; Hubeny, V.E.; Rangamani, M.; Shigemori, M.

    2009-01-01

    We study Brownian motion and the associated Langevin equation in AdS/CFT. The Brownian particle is realized in the bulk spacetime as a probe fundamental string in an asymptotically AdS black hole background, stretching between the AdS boundary and the horizon. The modes on the string are excited by

  4. Colliding waves on a string in AdS$_3$

    CERN Document Server

    Vegh, David

    2015-01-01

    This paper is concerned with the classical motion of a string in global AdS$_3$. The initially static string stretches between two antipodal points on the boundary circle. Both endpoints are perturbed which creates cusps at a steady rate. The cusps propagate towards the interior where they collide. The behavior of the string depends on the strength of forcing. Three qualitatively different phases can be distinguished: transparent, gray, and black. The transparent region is analogous to a standing wave. In the black phase, there is a horizon on the worldsheet and cusps never reach the other endpoint. The string keeps folding and its length grows linearly over time. In the gray phase, the string still grows linearly. However, cusps do cross to the other side. The transparent and gray regions are separated by a transition point where a logarithmic accumulation of cusps is numerically observed. A simple model reproduces the qualitative behavior of the string in the three phases.

  5. Bootstrapping Pure Quantum Gravity in AdS3

    CERN Document Server

    Bae, Jin-Beom; Lee, Sungjay

    2016-01-01

    The three-dimensional pure quantum gravity with negative cosmological constant is supposed to be dual to the extremal conformal field theory of central charge $c=24k$ in two dimensions. We employ the conformal bootstrap method to analyze the extremal CFTs, and find numerical evidence for the non-existence of the extremal CFTs for sufficiently large central charge ($k \\ge 20$). We also explore near-extremal CFTs, a small modification of extremal ones, and find similar evidence for their non-existence for large central charge. This indicates, under the assumption of holomorphic factorization, the pure gravity in the weakly curved AdS$_3$ do not exist as a consistent quantum theory.

  6. On jordanian deformations of AdS5 and supergravity

    Science.gov (United States)

    Hoare, Ben; van Tongeren, Stijn J.

    2016-10-01

    We consider various homogeneous Yang-Baxter deformations of the {{AdS}}5× {{{S}}}5 superstring that can be obtained from the η-deformed superstring and related models by singular boosts. The jordanian deformations we obtain in this way behave similarly to the η-deformed model with regard to supergravity: T dualizing the classical sigma model it is possible to find corresponding solutions of supergravity, which, however, have dilatons that prevent T dualizing back. Hence the backgrounds of these jordanian deformations are not solutions of supergravity. Still, they do satisfy a set of recently found modified supergravity equations which implies that the corresponding sigma models are scale invariant. The abelian models that we obtain by singular boosts do directly correspond to solutions of supergravity. In addition to our main results we consider contraction limits of our main example, which do correspond to supergravity solutions.

  7. On jordanian deformations of AdS_5 and supergravity

    CERN Document Server

    Hoare, Ben

    2016-01-01

    We consider various homogeneous Yang-Baxter deformations of the AdS_5 x S^5 superstring that can be obtained from the eta-deformed superstring and related models by singular boosts. The jordanian deformations we obtain in this way behave similarly to the eta-deformed model with regard to supergravity: T dualizing the classical sigma model it is possible to find corresponding solutions of supergravity, which, however, have dilatons that prevent T dualizing back. Hence the backgrounds of these jordanian deformations are not solutions of supergravity. Still, they do satisfy a set of recently found modified supergravity equations which should imply that the corresponding sigma models are scale invariant. The abelian models that we obtain by singular boosts do directly correspond to solutions of supergravity. In addition to our main results we consider contraction limits of our main example, which also do not correspond to supergravity solutions.

  8. Higher spins on AdS3 from the worldsheet

    Science.gov (United States)

    Ferreira, Kevin; Gaberdiel, Matthias R.; Jottar, Juan I.

    2017-07-01

    It was recently shown that the CFT dual of string theory on AdS3 × S3 × T 4, the symmetric orbifold of T 4, contains a closed higher spin subsector. Via holography, this makes precise the sense in which tensionless string theory on this background contains a Vasiliev higher spin theory. In this paper we study this phenomenon directly from the worldsheet. Using the WZW description of the background with pure NS-NS flux, we identify the states that make up the leading Regge trajectory and show that they fit into the even spin N=4 Vasiliev higher spin theory. We also show that these higher spin states do not become massless, except for the somewhat singular case of level k = 1 where the theory contains a stringy tower of massless higher spin fields coming from the long string sector.

  9. Thermodynamics of charged Lovelock: AdS black holes

    Science.gov (United States)

    Prasobh, C. B.; Suresh, Jishnu; Kuriakose, V. C.

    2016-04-01

    We investigate the thermodynamic behavior of maximally symmetric charged, asymptotically AdS black hole solutions of Lovelock gravity. We explore the thermodynamic stability of such solutions by the ordinary method of calculating the specific heat of the black holes and investigating its divergences which signal second-order phase transitions between black hole states. We then utilize the methods of thermodynamic geometry of black hole spacetimes in order to explain the origin of these points of divergence. We calculate the curvature scalar corresponding to a Legendre-invariant thermodynamic metric of these spacetimes and find that the divergences in the black hole specific heat correspond to singularities in the thermodynamic phase space. We also calculate the area spectrum for large black holes in the model by applying the Bohr-Sommerfeld quantization to the adiabatic invariant calculated for the spacetime.

  10. Jet physics from static charges in AdS space

    Science.gov (United States)

    Chien, Yang-Ting; Schwartz, Matthew D.; Simmons-Duffin, David; Stewart, Iain W.

    2012-02-01

    Soft interactions with high-energy jets are explored in radial coordinates which exploit the approximately conformal behavior of perturbative gauge theories. In these coordinates, the jets, approximated by Wilson lines, become static charges in Euclidean AdS. The anomalous dimension of the corresponding Wilson line operator is then determined by the potential energy of the charges. To study these Wilson lines we introduce a “conformal gauge” which does not have kinetic mixing between radial and angular directions, and show that a number of properties of Wilson lines are reproduced through relatively simple calculations. For example, certain nonplanar graphs involving multiple Wilson lines automatically vanish. We also discuss the linear growth of the charges’ imaginary potential energy with separation, and a relationship between Wilson line diagrams and Witten diagrams.

  11. Jet Physics from Static Charges in AdS

    CERN Document Server

    Chien, Yang-Ting; Simmons-Duffin, David; Stewart, Iain W

    2011-01-01

    Soft interactions with high-energy jets are explored in radial coordinates which exploit the approximately conformal behavior of perturbative gauge theories. In these coordinates, the jets, approximated by Wilson lines, become static charges in Euclidean AdS. The anomalous dimension of the corresponding Wilson line operator is then determined by the potential energy of the charges. To study these Wilson lines we introduce a "conformal gauge" which does not have kinetic mixing between radial and angular directions, and show that a number of properties of Wilson lines are reproduced through relatively simple calculations. For example, certain non-planar graphs involving multiple Wilson lines automatically vanish. We also discuss the linear growth of the charges' imaginary potential energy with separation, and a relationship between Wilson line diagrams and Witten diagrams.

  12. An Investigation of AdS2 Backreaction and Holography

    CERN Document Server

    Engelsöy, Julius; Verlinde, Herman

    2016-01-01

    We investigate a dilaton gravity model in AdS2 proposed by Almheiri and Polchinski and develop an 1D effective description in terms of a dynamical boundary time with a Schwarzian derivative action. We show that the effective model is equivalent to a 1D version of Liouville theory, and investigate its dynamics and symmetries via a standard canonical framework. We include the coupling to arbitrary conformal matter and analyze the effective action in the presence of possible sources. We compute commutators of local operators at large time separation, and match the result with the time shift due to a gravitational shockwave interaction. We study a black hole evaporation process and comment on the role of entropy in this model.

  13. On Information Loss in AdS$_3$/CFT$_2$

    CERN Document Server

    Fitzpatrick, A Liam; Li, Daliang; Wang, Junpu

    2016-01-01

    We discuss information loss from black hole physics in AdS$_3$, focusing on two sharp signatures infecting CFT$_2$ correlators at large central charge $c$: 'forbidden singularities' arising from Euclidean-time periodicity due to the effective Hawking temperature, and late-time exponential decay in the Lorentzian region. We study an infinite class of examples where forbidden singularities can be resolved by non-perturbative effects at finite $c$, and we show that the resolution has certain universal features that also apply in the general case. Analytically continuing to the Lorentzian regime, we find that the non-perturbative effects that resolve forbidden singularities qualitatively change the behavior of correlators at times $t \\sim S_{BH}$, the black hole entropy. This may resolve the exponential decay of correlators at late times in black hole backgrounds. By Borel resumming the $1/c$ expansion of exact examples, we explicitly identify 'information-restoring' effects from heavy states that should correspo...

  14. Supersymmetry Properties of AdS Supergravity Backgrounds

    Science.gov (United States)

    Beck, Samuel; Gutowski, Jan; Papadopoulos, George

    2017-01-01

    Anti-de Sitter supergravity backgrounds are of particular interest in light of the AdS/CFT correspondence, which relates them to dual conformal field theories on the boundary of the anti-de Sitter space. We have investigated the forms of the supersymmetries these backgrounds preserve by solving the Killing spinor equations on the anti-de Sitter components of these spaces. We have found that a supersymmetric AdSn background necessarily preserves 2⌊n/2⌋ k supersymmetries for n 0 . Additionally, we have found that the Killing spinors of each background are exactly the zeroes of a Dirac-like operator constructed from the Killing spinor equations.

  15. Thermodynamics of charged Lovelock: AdS black holes

    Energy Technology Data Exchange (ETDEWEB)

    Prasobh, C.B.; Suresh, Jishnu; Kuriakose, V.C. [Cochin University of Science and Technology, Department of Physics, Cochin (India)

    2016-04-15

    We investigate the thermodynamic behavior of maximally symmetric charged, asymptotically AdS black hole solutions of Lovelock gravity. We explore the thermodynamic stability of such solutions by the ordinary method of calculating the specific heat of the black holes and investigating its divergences which signal second-order phase transitions between black hole states. We then utilize the methods of thermodynamic geometry of black hole spacetimes in order to explain the origin of these points of divergence. We calculate the curvature scalar corresponding to a Legendre-invariant thermodynamic metric of these spacetimes and find that the divergences in the black hole specific heat correspond to singularities in the thermodynamic phase space. We also calculate the area spectrum for large black holes in the model by applying the Bohr-Sommerfeld quantization to the adiabatic invariant calculated for the spacetime. (orig.)

  16. Adiabatic pumping solutions in global AdS

    Science.gov (United States)

    Carracedo, Pablo; Mas, Javier; Musso, Daniele; Serantes, Alexandre

    2017-05-01

    We construct a family of very simple stationary solutions to gravity coupled to a massless scalar field in global AdS. They involve a constantly rising source for the scalar field at the boundary and thereby we name them pumping solutions. We construct them numerically in D = 4. They are regular and, generically, have negative mass. We perform a study of linear and nonlinear stability and find both stable and unstable branches. In the latter case, solutions belonging to different sub-branches can either decay to black holes or to limiting cycles. This observation motivates the search for non-stationary exactly timeperiodic solutions which we actually construct. We clarify the role of pumping solutions in the context of quasistatic adiabatic quenches. In D = 3 the pumping solutions can be related to other previously known solutions, like magnetic or translationally-breaking backgrounds. From this we derive an analytic expression.

  17. Worldsheet dilatation operator for the AdS superstring

    Energy Technology Data Exchange (ETDEWEB)

    Ramírez, Israel [Departamento de Física, Universidad Técnica Federico Santa María,Casilla 110-V, Valparaíso (Chile); Institut für Mathematik und Institut für Physik, Humboldt-Universität zu Berlin,IRIS Haus, Zum Großen Windkanal 6, 12489 Berlin (Germany); Vallilo, Brenno Carlini [Departamento de Ciencias Físicas, Universidad Andres Bello,Republica 220, Santiago (Chile)

    2016-05-23

    In this work we propose a systematic way to compute the logarithmic divergences of composite operators in the pure spinor description of the AdS{sub 5}×S{sup 5} superstring. The computations of these divergences can be summarized in terms of a dilatation operator acting on the local operators. We check our results with some important composite operators of the formalism.

  18. Islands of stability and recurrence times in AdS

    CERN Document Server

    Green, Stephen R; Lehner, Luis; Liebling, Steven L

    2015-01-01

    We study the stability of anti-de Sitter (AdS) spacetime to spherically symmetric perturbations of a real scalar field in general relativity. Further, we work within the context of the "two time framework" (TTF) approximation, which describes the leading nonlinear effects for small amplitude perturbations, and is therefore suitable for studying the weakly turbulent instability of AdS---including both collapsing and non-collapsing solutions. We have previously identified a class of quasi-periodic (QP) solutions to the TTF equations, and in this work we analyze their stability. We show that there exist several families of QP solutions that are stable to linear order, and we argue that these solutions represent islands of stability in TTF. We extract the eigenmodes of small oscillations about QP solutions, and we use them to predict approximate recurrence times for generic non-collapsing initial data in the full (non-TTF) system. Alternatively, when sufficient energy is driven to high-frequency modes, as occurs ...

  19. Holographic reconstruction of AdS exchanges from crossing symmetry

    Science.gov (United States)

    Alday, Luis F.; Bissi, Agnese; Perlmutter, Eric

    2017-08-01

    Motivated by AdS/CFT, we address the following outstanding question in large N conformal field theory: given the appearance of a single-trace operator in the O× O OPE of a scalar primary O , what is its total contribution to the vacuum four-point function theories at leading order in 1/ N. Viewed holographically, this provides a field theory reconstruction of crossing-symmetric, four-point exchange amplitudes in AdS5. Our solution takes the form of a resummation of the large spin solution to the crossing equations, supplemented by corrections at finite spin, required by crossing. The method can be applied to the exchange of operators of arbitrary twist τ and spin s, although it vastly simplifies for even-integer twist, where we give explicit results. The output is the set of OPE data for the exchange of all double-trace operators {[OO]}_{n,ℓ } . We find that the double-trace anomalous dimensions γ n, ℓ are negative, monotonic and convex functions of ℓ, for all n and all ℓ > s. This constitutes a holographic signature of bulk causality and classical dynamics of even-spin fields. We also find that the "derivative relation" between double-trace anomalous dimensions and OPE coefficients does not hold in general, and derive the explicit form of the deviation in several cases. Finally, we study large n limits of γ n,ℓ, relevant for the Regge and bulk-point regimes.

  20. AdS/CFT Duality User Guide

    CERN Document Server

    Natsuume, Makoto

    2014-01-01

    This is the draft version of a textbook on "real-world" applications of the AdS/CFT duality for beginning graduate students in particle physics and for researchers in the other fields. The aim of this book is to provide background materials such as string theory, general relativity, nuclear physics, nonequilibrium physics, and condensed-matter physics as well as some key applications of the AdS/CFT duality in a single textbook. Contents: (1) Introduction, (2) General relativity and black holes, (3) Black holes and thermodynamics, (4) Strong interaction and gauge theories, (5) The road to AdS/CFT, (6) The AdS spacetime, (7) AdS/CFT - equilibrium, (8) AdS/CFT - adding probes, (9) Basics of nonequilibrium physics, (10) AdS/CFT - nonequilibrium, (11) Other AdS spacetimes, (12) Applications to quark-gluon plasma, (13) Basics of phase transition, (14) AdS/CFT - phase transition.

  1. Facilities Management and Added Value

    DEFF Research Database (Denmark)

    Jensen, Per Anker

    2010-01-01

    Aim: This paper aims to present different models of the concept of the added value of Facilities Management (FM), including the FM Value Map, which forms the basis of research group in EuroFM, and to present some of the results of this research collaboration. Approach and methodology: The paper...... on the aimed output) and the internal resource based view (with a focus on the input from FM and RE). Good relationship management and building on trust shows to be equally important as delivering the agreed services. In order to measure the multi-dimensional components of adding value both qualitative...... is based on literature reviews of the most influential journals within the academic fields of FM, Corporate Real Estate Management and Business to Business Marketing and discussions between participants of the research group working on a further exploration and testing of the FM Value Map. Conclusions...

  2. The PredictAD project

    DEFF Research Database (Denmark)

    Antila, Kari; Lötjönen, Jyrki; Thurfjell, Lennart;

    2013-01-01

    can be managed. Today the significance of early and precise diagnosis of AD is emphasized in order to minimize its irreversible effects on the nervous system. When new drugs and therapies enter the market it is also vital to effectively identify the right candidates to benefit from these. The main...... candidates and implement the framework in software. The results are currently used in several research projects, licensed to commercial use and being tested for clinical use in several trials....

  3. Scattering States in AdS/CFT

    Energy Technology Data Exchange (ETDEWEB)

    Fitzpatrick, A.Liam; /Boston U.; Kaplan, Jared; /SLAC

    2012-02-14

    We show that suitably regulated multi-trace primary states in large N CFTs behave like 'in' and 'out' scattering states in the flat-space limit of AdS. Their transition matrix elements approach the exact scattering amplitudes for the bulk theory, providing a natural CFT definition of the flat space S-Matrix. We study corrections resulting from the AdS curvature and particle propagation far from the center of AdS, and show that AdS simply provides an IR regulator that disappears in the flat space limit.

  4. Holography in 3D AdS gravity with torsion

    CERN Document Server

    Blagojević, Milutin; Miskovic, Olivera; Olea, Rodrigo

    2013-01-01

    Basic aspects of the AdS/CFT correspondence are studied in the framework of 3-dimensional gravity with torsion. After choosing a consistent holographic ansatz, we formulate an improved approach to the Noether--Ward identities for the boundary theory. The method is applied first to the topological Mielke--Baekler model, and then to the more interesting (parity-preserving) 3-dimensional gravity with propagating torsion. In both cases, we find the finite holographic energy-momentum and spin currents and obtain the associated (anomalous) Noether--Ward identities.

  5. Towards Timelike Singularity via AdS Dual

    CERN Document Server

    Bhowmick, Samrat

    2016-01-01

    It is well known that Kasner geometry with spacelike singularity can be extended to bulk AdS-like geometry, furthermore one can study field theory on this Kasner space via its gravity dual. In this paper, we show that there exists a Kasner-like geometry with timelike singularity for which one can construct a dual gravity description. We then study various minimal surfaces including spacelike geodesics. Finally, we compute correlators of highly massive operators in the boundary field theory with a geodesic approximation.

  6. Canonical energy and hairy AdS black holes

    CERN Document Server

    Hyun, Seungjoon; Yi, Sang-Heon

    2016-01-01

    We propose the modified version of the canonical energy which was introduced originally by Hollands and Wald. Our construction depends only on the Euler-Lagrange expression of the system and thus is independent of the ambiguity in the Lagrangian. After some comments on our construction, we briefly mention on the relevance of our construction to the boundary information metric in the context of the AdS/CFT correspondence. We also study the stability of three-dimensional hairy extremal black holes by using our construction.

  7. Stability of Charged Global AdS$_4$ Spacetimes

    CERN Document Server

    Arias, Raúl; Serantes, Alexandre

    2016-01-01

    We study linear and nonlinear stability of asymptotically AdS$_4$ solutions in Einstein-Maxwell-scalar theory. After summarizing the set of static solutions we first examine thermodynamical stability in the grand canonical ensemble and the phase transitions that occur among them. In the second part of the paper we focus on nonlinear stability in the microcanonical ensemble by evolving radial perturbations numerically. We find hints of an instability corner for vanishingly small perturbations of the same kind as the ones present in the uncharged case. Collapses are avoided, instead, if the charge and mass of the perturbations come to close the line of solitons. Finally we examine the soliton solutions. The linear spectrum of normal modes is not resonant and instability turns on at extrema of the mass curve. Linear stability extends to nonlinear stability up to some threshold for the amplitude of the perturbation. Beyond that, the soliton is destroyed and collapses to a hairy black hole. The relative width of t...

  8. AdS crunches, CFT falls, and cosmological complexity

    CERN Document Server

    Barbón, José Luis

    2015-01-01

    This chapter discusses the holographic description of crunching AdS cosmologies. Crunching FRW models with hyperbolic spatial sections are dual to semiclassical condensates in deformed de Sitter (dS) CFTs. dS-invariant condensates with a sharply defined energy scale are induced by effective negative-definite relevant or marginal operators, which may or may not destabilize the CFT. This result is obtained by explicitly constructing a “complementarity map” for this model, given by a conformal transformation of the dS CFT into a static time-frame, which reveals the crunch as an infinite potential-energy fall in finite time. Quite generically, the crunch is associated with a finite-mass black hole if the dS O(d, 1) invariance is an accidental IR symmetry, broken to U(1) × O(d) in the UV. Any such regularization cuts off the eternity of dS spacetime. Equivalently, the dimension of the Hilbert space propagating into the crunch is finite only when dS is not eternal.

  9. F-theory and AdS3/CFT2

    Science.gov (United States)

    Couzens, Christopher; Lawrie, Craig; Martelli, Dario; Schäfer-Nameki, Sakura; Wong, Jin-Mann

    2017-08-01

    We construct supersymmetric AdS3 solutions in F-theory, that is Type IIB supergravity with varying axio-dilaton, which are holographically dual to 2d N=(0,4) superconformal field theories with small superconformal algebra. In F-theory these arise from D3-branes wrapped on curves in the base of an elliptically fibered Calabi-Yau threefold Y 3 and correspond to self-dual strings in the 6d N=(1,0) theory obtained from F-theory on Y 3. The non-trivial fibration over the wrapped curves implies a varying coupling of the N=4 Super-Yang-Mills theory on the D3-branes. We compute the holographic central charges and show that these agree with the field theory and with the anomalies of self-dual strings in 6d. We complement our analysis with a discussion of the dual M-theory solutions and a comparison of the central charges.

  10. On modular properties of the AdS3 CFT

    CERN Document Server

    Baron, Walter

    2010-01-01

    We study modular properties of the AdS3 WZNW model. Although the Euclidean partition function is modular invariant, the characters on the Euclidean torus are ill-defined and their modular transformations are unknown. We reconsider the characters defined on the Lorentzian torus, focusing on their structure as distributions. We find a generalized S matrix, depending on the sign of the real modular parameters, which has two diagonal blocks and one off-diagonal block, mixing discrete and continuous representations, that we fully determine. We then explore the relations among the modular transformations, the fusion algebra and the boundary states. We explicitly construct Ishibashi states for the maximally symmetric D-branes and show that the generalized S matrix defines the one-point functions associated to point-like and H2 branes as well as the fusion rules of the degenerate representations of SL(2,R) appearing in the open string spectrum of the point-like D-branes, through a generalized Verlinde theorem.

  11. The ADS All Sky Survey

    Science.gov (United States)

    Goodman, Alyssa

    We will create the first interactive sky map of astronomers' understanding of the Universe over time. We will accomplish this goal by turning the NASA Astrophysics Data System (ADS), widely known for its unrivaled value as a literature resource, into a data resource. GIS and GPS systems have made it commonplace to see and explore information about goings-on on Earth in the context of maps and timelines. Our proposal shows an example of a program that lets a user explore which countries have been mentioned in the New York Times, on what dates, and in what kinds of articles. By analogy, the goal of our project is to enable this kind of exploration-on the sky-for the full corpus of astrophysical literature available through ADS. Our group's expertise and collaborations uniquely position us to create this interactive sky map of the literature, which we call the "ADS All-Sky Survey." To create this survey, here are the principal steps we need to follow. First, by analogy to "geotagging," we will "astrotag," the ADS literature. Many "astrotags" effectively already exist, thanks to curation efforts at both CDS and NED. These efforts have created links to "source" positions on the sky associated with each of the millions of articles in the ADS. Our collaboration with ADS and CDS will let us automatically extract astrotags for all existing and future ADS holdings. The new ADS Labs, which our group helps to develop, includes the ability for researchers to filter article search results using a variety of "facets" (e.g. sources, keywords, authors, observatories, etc.). Using only extracted astrotags and facets, we can create functionality like what is described in the Times example above: we can offer a map of the density of positions' "mentions" on the sky, filterable by the properties of those mentions. Using this map, researchers will be able to interactively, visually, discover what regions have been studied for what reasons, at what times, and by whom. Second, where

  12. Noncommutative AdS2/CFT1 duality: The case of massless scalar fields

    Science.gov (United States)

    Pinzul, A.; Stern, A.

    2017-09-01

    We show how to construct correlators for the CFT1 which is dual to noncommutative AdS2 (n c AdS2). We do it explicitly for the example of the massless scalar field on Euclidean n c AdS2. n c AdS2 is the quantization of AdS2 that preserves all the isometries. It is described in terms of the unitary irreducible representations, more specifically discrete series representations, of s o (2 ,1 ). We write down symmetric differential representations for the discrete series and then map them to functions on the Moyal-Weyl plane. The Moyal-Weyl plane has a large distance limit which can be identified with the boundary of n c AdS2. Killing vectors can be constructed on n c AdS2 which reduce to the AdS2 Killing vectors near the boundary. We, therefore, conclude that n c AdS2 is asymptotically AdS2, and so the AdS /CFT correspondence should apply. For the example of the massless scalar field on Euclidean n c AdS2, the on-shell action, and resulting two-point function for the boundary theory, are computed to leading order in the noncommutativity parameter. The computation is nontrivial because nonlocal interactions appear in the Moyal-Weyl description. Nevertheless, the result is remarkably simple and agrees with that of the commutative scalar field theory, up to a rescaling.

  13. Entanglement Entropy of AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Maurizio Melis

    2010-11-01

    Full Text Available We review recent progress in understanding the entanglement entropy of gravitational configurations for anti-de Sitter gravity in two and three spacetime dimensions using the AdS/CFT correspondence. We derive simple expressions for the entanglement entropy of two- and three-dimensional black holes. In both cases, the leading term of the entanglement entropy in the large black hole mass expansion reproduces exactly the Bekenstein-Hawking entropy, whereas the subleading term behaves logarithmically. In particular, for the BTZ black hole the leading term of the entanglement entropy can be obtained from the large temperature expansion of the partition function of a broad class of 2D CFTs on the torus.

  14. MUSICAL ARRANGEMENT OF MEDIA ADS

    Directory of Open Access Journals (Sweden)

    Chernyshov Alexander V.

    2015-01-01

    Full Text Available The music-compositional principles of commercial and political advertising and also the self-promotion of electronic media (radio, television, Internet are considered in this mediatext: from the elementary beeps, symbolic functions, emblems/logos and musical brands to the sound engineering technology to underscore the product's name and the complex synthesis between music and intra movements and color-light design of frames. Simultaneously examines, how the musical arrangement of ethereal advertising is involved in creation the emotional drama or bravado which reach the level of explicit or associative counterpoint 'music with the advertised object or subject' and which extend to expression of cultural image of all the broadcast channel. The article explores the works of the next genres like infomercial, teleshopping, film-ad, and autonomous commercials that have been produced in European countries or USA.

  15. Ad valorem versus unit taxes

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Sørensen, Allan

    2010-01-01

    Real-world industries are composed from heterogeneous firms and substantial intra-industry reallocations take place, i.e. high productivity firms squeeze out low productivity firms. Previous tax-tool comparisons have not included these central forces of industry structure. This paper examines...... a general equilibrium monopolistic competition model with heterogeneous firms and intra-industry reallocations. We show that the welfare superiority of ad valorem over unit taxes under imperfect competition is not only preserved but amplified. The additional difference between the tools arises because unit...... taxes distort relative prices, which in turn reduces average industry productivity through reallocations (the survival and increased market share of lower productivity firms). Importantly, numerical solutions of the model reveal that the relative welfare loss from using the unit tax increases...

  16. Adding timing to the VELO

    CERN Document Server

    Mitreska, Biljana

    2017-01-01

    The LHCb experiment is designed to perform high precision measurements of matter-antimatter asymmetries and searches for rare and forbidden decays, with the aim of discovering new and unexpected particles and forces. In 2030 the LHC beam intensity will increase by a factor of 50 compared to current operations. This means increased samples of the particles we need to study, but it also presents experimental challenges. In particular, with current technology it becomes impossible to differentiate the many (>50) separate proton-proton collisions which occur for each bunch crossing.\\\\ In this project a Monte Carlo simulation was developed to model the operation of a silicon pixel vertex detector surrounding the collision region at LHCb, under the conditions expected after 2030, after the second upgrade of the Vertex Locator(VELO).The main goal was studying the effect of adding '4D' detectors which save high-precision timing information, in addition to the usual three spatial coordinates, as charged particles pas...

  17. Stringy Membranes in AdS/CFT

    CERN Document Server

    Axenides, Minos; Linardopoulos, Georgios

    2013-01-01

    We study membrane configurations in AdS_{7/4}xS^{4/7}. The membranes are wrapped around the compact manifold S^{4/7} and are dynamically equivalent to bosonic strings in AdS_5. We thus conveniently identify them as "stringy membranes". For the case of AdS_7xS^4, their construction is carried out by embedding the Polyakov action for classical bosonic strings in AdS_5, into the corresponding membrane action. Therefore, every string configuration in AdS_5 can be realized by an appropriately chosen stringy membrane in AdS_7xS^4. We discuss the possibility of this being also the case for stringy membranes in AdS_4xS^7/Z^k (k > 1 or k = 1). By performing a stability analysis to the constructed solutions, we find that the (membrane) fluctuations along their transverse directions are organized in multiple Lam\\'{e} stability bands and gaps in the space of parameters of the configurations. In this membrane picture, strings exhibit a single band/gap structure. Since the spectrum of quadratic fluctuations is important fo...

  18. Spiky strings in AdS_3 x S^1 and their AdS-pp-wave limits

    CERN Document Server

    Ishizeki, R; Tirziu, A; Tseytlin, A A

    2008-01-01

    We study a class of classical solutions for closed strings moving in AdS_3 x S^1 part of AdS_5 x S^5 with energy E and spin S in AdS_3 and angular momentum J and winding m in S^1. They have rigid shape with n spikes in AdS_3. We find that when J or m are non-zero, the spikes do not end in cusps. We consider in detail a special large n limit in which S ~ n^2, J ~ n, i.e. S >> J >> 1, with (E+S)/ n^2, (E-S)/ n, J/n, m/n staying finite. In that limit the spiky spinning string approaches the boundary of AdS_5. We show that the corresponding solution can be interpreted as describing a periodic-spike string moving in AdS_3 --pp-wave x S^1 background. The resulting expression for the string energy should represent a strong-coupling prediction for anomalous dimension of a class of dual gauge theory states in a particular thermodynamic limit of the SL(2) spin chain.

  19. Recurring Anomaly Detection System (ReADS)

    Data.gov (United States)

    National Aeronautics and Space Administration — Overview: ReADS can analyze text reports, such as aviation reports and problem or maintenance records. ReADS uses text clustering algorithms to group loosely related...

  20. TV Snack Ads Make Preschoolers Snack More

    Science.gov (United States)

    ... Sesame Street" interrupted by TV ads for a salty snack food ended up eating more of that ... watched the show with commercials for a popular salty snack. The ads depicted kids happily playing and ...

  1. The AdS/CFT/Unparticle Correspondence

    CERN Document Server

    Cacciapaglia, Giacomo; Terning, John

    2009-01-01

    We examine the correspondence between the anti-de Sitter (AdS) description of conformal field theories (CFTs) and the unparticle description of CFTs. We show how unparticle actions are equivalent to holographic boundary actions for fields in AdS, and how massive unparticles provide a new type of infrared cutoff that can be simply implemented in AdS by a soft breaking of conformal symmetry. We also show that processes involving scalar unparticles with dimensions d_s<2 or fermion unparticles with dimensions d_f<5/2 are insensitive to ultraviolet cutoff effects. Finally we show that gauge interactions for unparticles can be described by bulk gauge interactions in AdS and that they correspond to minimal gauging of the non-local effective action, and we compute the fermion unparticle production cross-section.

  2. TASI lectures on AdS/CFT

    CERN Document Server

    Penedones, Joao

    2017-01-01

    We introduce the AdS/CFT correspondence as a natural extension of QFT in a fixed AdS background. We start by reviewing some general concepts of CFT, including the embedding space formalism. We then consider QFT in a fixed AdS background and show that one can define boundary operators that enjoy very similar properties as in a CFT, except for the lack of a stress tensor. Including a dynamical metric in AdS generates a boundary stress tensor and completes the CFT axioms. We also discuss some applications of the bulk geometric intuition to strongly coupled QFT. Finally, we end with a review of the main properties of Mellin amplitudes for CFT correlation functions and their uses in the context of AdS/CFT.

  3. Condom ads promote illicit sex.

    Science.gov (United States)

    Kippley, J F

    1994-01-01

    Written in 1987, this opinion was republished in the wake of US President Bill Clinton's AIDS prevention media campaign promoting condom use which began January 1994, targeted at young adults aged 18-25. The author staunchly opposes condom use even though he admits that people do not consider abstinence from sex to be a serious option for the prevention of HIV/STD infection. He believes that there is no moral use of sex with a condom and that condoms have always been a sign of immorality, be it prostitution, adultery, fornication, or marital contraception. Likewise, the author laments the success enjoyed by Planned Parenthood in achieving the social acceptance of marital contraception and sex outside of marriage. The complete social acceptance of homosexual activity, however, remains to be achieved. Magazines, newspapers, and television receive income in exchange for publishing or airing advertisements. Finding offensive advertisements which promote the use of condoms against HIV infection, the author recommends writing letters of complaint to the responsible media sources. If the television stations or publications in question continue to advertise condoms to the public, stop watching them or end one's subscriptions to the particular printed media. Such action taken collectively among many individuals will reduce product sales and income, and potentially sway corporate policy against condom ads.

  4. Security Ads in Mobile Apps

    Directory of Open Access Journals (Sweden)

    Manasvi Kalra,

    2016-02-01

    Full Text Available The apps consist of advertisements to promote their products. Not all of them are appropriate to resume. Therefore various algorithms have been used in order to block those apps from existence but none of them is completely successful. In our app we are using an antivirus which can by default block those spy apps and remove them from the web page. The algorithm which has been used makes use of various ant viruses in the background which detect irrelevant and intimate apps and then our algorithm will demolish them. Certain apps are non-trustworthy where one click can spy all the mobile data. They block those apps and works on security. We are working on secure ads for mobile apps. It can also work as a basic antivirus where it detects the viruses like malwares in any of your installed apps or downloads. It will create a popup of discarding or keeping it. Mobile applications can be downloaded from anywhere like amazon, googleplay, apps store etc. There is no rigorous verification of an application when it is uploaded to the market. One can easily develop a malicious application and upload it to the app market. The user itself is responsible for accepting the risk of an app available from secondary markets. Therefore, we have decided to develop this app to make the market more secure and bounded. In future, It will take the mobile market while consuming minimal additional resources and preserving user privacy.

  5. Material Developing for ADS Beam Window

    Institute of Scientific and Technical Information of China (English)

    XUYong-li; XUYuan-chao; LIHua-qing; NINGGuang-sheng; WANFa-rong; ZHAOFei

    2003-01-01

    The irradiation damage and the chemical interaction with the coolant for the ADS target and the structure materials are the key issues in ADS engineering. The developing of the materials that are irradiation and corrosion resistance is the important topic in ADS program in many countries. In this case,a topic of the material developing for the beam window has been proposed in our ADS program.

  6. Myths & Facts about Value-Added Analysis

    Science.gov (United States)

    TNTP, 2011

    2011-01-01

    This paper presents myths as well as facts about value-added analysis. These myths include: (1) "Value-added isn't fair to teachers who work in high-need schools, where students tend to lag far behind academically"; (2) "Value-added scores are too volatile from year-to-year to be trusted"; (3) "There's no research behind value-added"; (4) "Using…

  7. Automated Experiments on Ad Privacy Settings

    Directory of Open Access Journals (Sweden)

    Datta Amit

    2015-04-01

    Full Text Available To partly address people’s concerns over web tracking, Google has created the Ad Settings webpage to provide information about and some choice over the profiles Google creates on users. We present AdFisher, an automated tool that explores how user behaviors, Google’s ads, and Ad Settings interact. AdFisher can run browser-based experiments and analyze data using machine learning and significance tests. Our tool uses a rigorous experimental design and statistical analysis to ensure the statistical soundness of our results. We use AdFisher to find that the Ad Settings was opaque about some features of a user’s profile, that it does provide some choice on ads, and that these choices can lead to seemingly discriminatory ads. In particular, we found that visiting webpages associated with substance abuse changed the ads shown but not the settings page. We also found that setting the gender to female resulted in getting fewer instances of an ad related to high paying jobs than setting it to male. We cannot determine who caused these findings due to our limited visibility into the ad ecosystem, which includes Google, advertisers, websites, and users. Nevertheless, these results can form the starting point for deeper investigations by either the companies themselves or by regulatory bodies.

  8. 16 CFR 460.18 - Insulation ads.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Insulation ads. 460.18 Section 460.18 Commercial Practices FEDERAL TRADE COMMISSION TRADE REGULATION RULES LABELING AND ADVERTISING OF HOME INSULATION § 460.18 Insulation ads. (a) If your ad gives an R-value, you must give the type of insulation...

  9. Ad-Coop Positioning System (ACPS)

    DEFF Research Database (Denmark)

    Frattasi, Simone; Monti, Marco

    2008-01-01

    In this paper, we propose an innovative solution for positioning determination in 4G wireless networks by introducing the Ad-Coop Positioning System (ACPS). The ACPS is supported by a hybrid cellular ad-hoc architecture, where the cellular network has a centralized control over the ad...

  10. Supergravity on $AdS_{5/4}$ x Hopf Fibrations and Conformal Field Theories

    CERN Document Server

    Halyo, E

    2000-01-01

    We obtain three and four dimensional conformal field theories with less than maximal supersymmetry by using their supergravity duals. These supergravity theories are type II on $AdS_5 \\times CP^2$, IIA on $AdS_4 \\times CP^3$, IIB on $AdS_5 \\times S^5/Z_k$ and D=11 supergravity on $AdS_4 \\times S^7/Z_k$. They are obtained from the spherically compactified ten and eleven dimensional theories by either Hopf reduction or by winding the U(1) fiber over the base.

  11. Supergravity on $AdS_{5/4} \\times$ Hopf Fibrations and Conformal Field Theories

    OpenAIRE

    1998-01-01

    We obtain three and four dimensional conformal field theories with less than maximal supersymmetry by using their supergravity duals. These supergravity theories are type II on $AdS_5 \\times CP^2$, IIA on $AdS_4 \\times CP^3$, IIB on $AdS_5 \\times S^5/Z_k$ and D=11 supergravity on $AdS_4 \\times S^7/Z_k$. They are obtained from the spherically compactified ten and eleven dimensional theories by either Hopf reduction or by winding the U(1) fiber over the base.

  12. Protein domain organisation: adding order

    Directory of Open Access Journals (Sweden)

    Kummerfeld Sarah K

    2009-01-01

    Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

  13. Flat Currents of Green-Schwarz Superstring in AdS2 × S2 Background

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    From the κ symmetric action of ⅡB string in AdS2 × S2 background given by Zhou, we derive the equations of motion. By using the twisted dual transformation which was introduced by Hou, we construct the flat currents, conserving non-local charge with one free parameter, for the superstring in AdS2 × S2.

  14. Joule-Thomson expansion of the charged AdS black holes

    Science.gov (United States)

    Ökcü, Özgür; Aydıner, Ekrem

    2017-01-01

    In this paper, we study Joule-Thomson effects for charged AdS black holes. We obtain inversion temperatures and curves. We investigate similarities and differences between van der Waals fluids and charged AdS black holes for the expansion. We obtain isenthalpic curves for both systems in the T- P plane and determine the cooling-heating regions.

  15. Joule-Thomson Expansion of Charged AdS Black Holes

    CERN Document Server

    Ökcü, Özgür

    2016-01-01

    In this paper, we study Joule-Thomson effects for charged AdS black holes. We obtain inversion temperatures and curves. We investigate similarities and differences between van der Waals fluids and charged AdS black holes for the expansion. We obtain isenthalpic curves for both systems in $T-P$ plane and determine the cooling-heating regions.

  16. Static Einstein-Maxwell Black Holes with No Spatial Isometries in AdS Space.

    Science.gov (United States)

    Herdeiro, Carlos A R; Radu, Eugen

    2016-11-25

    We explicitly construct static black hole solutions to the fully nonlinear, D=4, Einstein-Maxwell-anti-de Sitter (AdS) equations that have no continuous spatial symmetries. These black holes have a smooth, topologically spherical horizon (section), but without isometries, and approach, asymptotically, global AdS spacetime. They are interpreted as bound states of a horizon with the Einstein-Maxwell-AdS solitons recently discovered, for appropriate boundary data. In sharp contrast to the uniqueness results for a Minkowski electrovacuum, the existence of these black holes shows that single, equilibrium, black hole solutions in an AdS electrovacuum admit an arbitrary multipole structure.

  17. Static Einstein-Maxwell Black Holes with No Spatial Isometries in AdS Space

    Science.gov (United States)

    Herdeiro, Carlos A. R.; Radu, Eugen

    2016-11-01

    We explicitly construct static black hole solutions to the fully nonlinear, D =4 , Einstein-Maxwell-anti-de Sitter (AdS) equations that have no continuous spatial symmetries. These black holes have a smooth, topologically spherical horizon (section), but without isometries, and approach, asymptotically, global AdS spacetime. They are interpreted as bound states of a horizon with the Einstein-Maxwell-AdS solitons recently discovered, for appropriate boundary data. In sharp contrast to the uniqueness results for a Minkowski electrovacuum, the existence of these black holes shows that single, equilibrium, black hole solutions in an AdS electrovacuum admit an arbitrary multipole structure.

  18. Effects of ad placement and type on consumer responses to podcast ads.

    Science.gov (United States)

    Ritter, Eric A; Cho, Chang-Hoan

    2009-10-01

    The purpose of this study was to understand the effects of podcast ad placement and podcast ad type on consumers' perceived intrusiveness, perceived irritation, attitude toward the ad, and ad avoidance. Our 2 x 2 (traditional ad vs. sponsorship by beginning vs. middle) experimental study found that sponsorships generated better consumer responses than did traditional ads and that podcast ads placed at the beginning of audio podcasts yielded better consumer responses than those placed in the middle. Implications for marketers and advertisers are discussed.

  19. AdS perturbations, isometries, selection rules and the Higgs oscillator

    Energy Technology Data Exchange (ETDEWEB)

    Evnin, Oleg [Department of Physics, Faculty of Science, Chulalongkorn University,Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand); Theoretische Natuurkunde, Vrije Universiteit Brussel and The International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium); Nivesvivat, Rongvoram [Department of Physics, Faculty of Science, Chulalongkorn University,Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand)

    2016-01-25

    Dynamics of small-amplitude perturbations in the global anti-de Sitter (AdS) spacetime is restricted by selection rules that forbid effective energy transfer between certain sets of normal modes. The selection rules arise algebraically because some integrals of products of AdS mode functions vanish. Here, we reveal the relation of these selection rules to AdS isometries. The formulation we discover through this systematic approach is both simpler and stronger than what has been reported previously. In addition to the selection rule considerations, we develop a number of useful representations for the global AdS mode functions, with connections to algebraic structures of the Higgs oscillator, a superintegrable system describing a particle on a sphere in an inverse cosine-squared potential, where the AdS isometries play the role of a spectrum-generating algebra.

  20. Perceived threat of Alzheimer disease (AD): the role of personal experience with AD.

    Science.gov (United States)

    Suhr, Julie A; Kinkela, Jessica H

    2007-01-01

    The fear of developing Alzheimer disease (AD) is highly salient, particularly for biologic family members. The current study evaluated social/cognitive explanations for perceived AD threat beyond genetic relatedness, including personal experience with AD, belief in negative aging stereotypes, and performance on delayed memory tasks. Participants were 97 healthy older adults aged 50 to 85, self-referred for a free community memory screen. Results showed that, as expected, personal AD experience was related to perceived AD threat. Furthermore, consistent with expectations, AD experience moderated the relationship between perceived AD threat and other explanatory variables, including age, belief in negative aging stereotypes, and cognitive performance. In those with AD experience, whether genetic or not, younger age was associated with more perceived AD threat, but an inverse relationship was seen in those without AD experience. Those with genetic AD experience seem particularly vulnerable to the effects of negative age stereotype beliefs on perceived AD threat, and show an inverse relationship between their actual cognitive performance and their perception of personal AD threat. Results highlight the importance of considering personal experience with AD when assessing a person's self-reported concerns about AD or his/her own memory changes.

  1. Exploring antismoking ads: appeals, themes, and consequences.

    Science.gov (United States)

    Beaudoin, Christopher E

    2002-01-01

    In this study we seek a descriptive understanding of antismoking television advertising in light of the problem cigarette consumption poses for society today. We establish relationships between ad characteristics and whether ads have a youth or adult orientation, based on a content analysis of 197 antismoking television advertisements produced between 1991 and 1999. The study finds that youth-oriented ads have youth characters, sociability, and humor as common appeals, and social and short-term consequences. In contrast, adult-oriented ads relied on fear appeals and long-term, health-related consequences.

  2. From path integrals to tensor networks for the AdS /CFT correspondence

    Science.gov (United States)

    Miyaji, Masamichi; Takayanagi, Tadashi; Watanabe, Kento

    2017-03-01

    In this paper, we discuss tensor network descriptions of AdS /CFT from two different viewpoints. First, we start with a Euclidean path-integral computation of ground state wave functions with a UV cutoff. We consider its efficient optimization by making its UV cutoff position dependent and define a quantum state at each length scale. We conjecture that this path integral corresponds to a time slice of anti-de Sitter (AdS) spacetime. Next, we derive a flow of quantum states by rewriting the action of Killing vectors of AdS3 in terms of the dual two-dimensional conformal field theory (CFT). Both approaches support a correspondence between the hyperbolic time slice H2 in AdS3 and a version of continuous multiscale entanglement renormalization ansatz. We also give a heuristic argument about why we can expect a sub-AdS scale bulk locality for holographic CFTs.

  3. Value added meat marketing around the globe

    DEFF Research Database (Denmark)

    Grebitus, Carola; Mueller Loose, Simone

    In highly competitive meat markets it is important to offer value added products to consumers. Thus, we need to understand which attributes are especially valued by consumers. This track session will contribute to a better understanding of consumer preferences for value added meats across differe...

  4. Status Report on the Antiproton Decelerator (AD)

    CERN Document Server

    Erikson, T; Möhl, D

    2001-01-01

    CERN's new Antiproton Decelerator (AD) has been delivering a 100 MeV/c antiproton beam to three experiments (ASACUSA, AHENA and ATRAP) since July 10th, 2000. In this status report, we summarise the initial performance of the AD, draw provisional conclusions from the first month of operation and finally give some prospects for the future.

  5. On circular strings in (AdS3 × S 3)ϰ

    Science.gov (United States)

    Banerjee, Aritra; Panigrahi, Kamal L.

    2016-09-01

    The so called one-parameter (often called ϰ) deformed AdS string sigma models have attracted a lot of attention lately in the study of integrability in string theory. We construct various circular string solutions in the (AdS3 × S 3) ϰ background and describe the characteristics of such solutions qualitatively. We study the Bohr-Sommerfeld like quantization for these string states to characterise the motion. Further we find a `long' string limit of such circular strings in the ϰ-deformed AdS3 and find a novel dependence of the oscillation number on the energy in the next to leading order expansion.

  6. On circular strings in $(AdS_3 \\times S^3)_{\\varkappa}$

    CERN Document Server

    Banerjee, Aritra

    2016-01-01

    The so called one-parameter (often called $\\varkappa$) deformed $AdS$ string sigma models have attracted a lot of attention lately in the study of integrability in string theory. We construct various circular string solutions in the $(AdS_3 \\times S^3)_{\\varkappa}$ background and describe the characteristics of such solutions qualitatively. We study the Bohr-Sommerfeld like quantization for these string states to characterise the motion. Further we find a `long' string limit of such circular strings in the $\\varkappa$-deformed $AdS_3$ and find a novel dependence of the oscillation number on the energy in the next to leading order expansion.

  7. Various types of phase transitions in the AdS soliton background

    CERN Document Server

    Peng, Yan; Wang, Bin

    2011-01-01

    We study the basic holographic insulator and superconductor phase transition in the AdS soliton background by generalizing the spontaneous breaking of a global U(1) symmetry to occur via St$\\ddot{u}$ckelberg mechanism. We construct the soliton solutions with backreaction and examine the effects of the backreaction on the condensation of the scalar hair in the generalized St$\\ddot{u}$ckelberg Lagrangian. We disclose rich physics in various phase transitions. In addition to the AdS soliton configuration, we also examine the property of the phase transition in the AdS black hole background.

  8. Thermodynamic geometry and phase transitions of AdS braneworld black holes

    Science.gov (United States)

    Chaturvedi, Pankaj; Sengupta, Gautam

    2017-02-01

    The thermodynamics and phase transitions of charged RN-AdS and rotating Kerr-AdS black holes in a generalized Randall-Sundrum braneworld are investigated in the framework of thermodynamic geometry. A detailed analysis of the thermodynamics, stability and phase structures in the canonical and the grand canonical ensembles for these AdS braneworld black holes are described. The thermodynamic curvatures for both these AdS braneworld black holes are computed and studied as a function of the thermodynamic variables. Through this analysis we illustrate an interesting dependence of the phase structures on the braneworld parameter for these black holes.

  9. Google Advertising Tools Cashing in with AdSense and AdWords

    CERN Document Server

    Davis, Harold

    2010-01-01

    With this book, you'll learn how to take full advantage of Google AdWords and AdSense, the sophisticated online advertising tools used by thousands of large and small businesses. This new edition provides a substantially updated guide to advertising on the Web, including how it works in general, and how Google's advertising programs in particular help you make money. You'll find everything you need to work with AdWords, which lets you generate text ads to accompany specific search term results, and AdSense, which automatically delivers precisely targeted text and image ads to your website.

  10. Entropy of Warped Taub-NUT AdS Black String via the Brick Wall Method

    CERN Document Server

    Lee, Chong Oh

    2014-01-01

    When we consider five-dimensional warped Taub-NUT AdS black string with minimally coupled massive scalar field, we calculate an entropy by using the brick wall method. In extremely light effective mass, we find the entropy is proportional to an extra dimension wave number as well as quadratically divergent in a cutoff parameter. After taking zero NUT charge, we find the entropy of warped (AdS) Schwartzshield black hole string has a similar properties in as warped Taub-NUT AdS black string.

  11. Holographic complexity and fidelity susceptibility as holographic information dual to different volumes in AdS

    Directory of Open Access Journals (Sweden)

    N.S. Mazhari

    2017-03-01

    Full Text Available The holographic complexity and fidelity susceptibility have been defined as new quantities dual to different volumes in AdS. In this paper, we will use these new proposals to calculate both of these quantities for a variety of interesting deformations of AdS. We obtain the holographic complexity and fidelity susceptibility for an AdS black hole, Janus solution, a solution with cylindrical symmetry, an inhomogeneous background and a hyperscaling violating background. It is observed that the holographic complexity depends on the size of the subsystem for all these solutions and the fidelity susceptibility does not have any such dependence.

  12. Beyond the unitarity bound in AdS/CFT{sub (A)dS}

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Tomas [University of California, Santa Barbara (United States); Uhlemann, Christoph [Universitaet Wuerzburg (Germany)

    2012-07-01

    We study CFTs on dS and AdS spacetimes from a holographic perspective, in particular how the unitarity properties of the boundary theory are reflected in the bulk description. On geometries with an (A)dS conformal boundary we choose mass and boundary conditions for a Klein-Gordon field such that the corresponding CFT operator violates the unitarity bound. We analyze how the non-unitarity is reproduced in the bulk and discuss, for the case of an AdS boundary, prospects for multi-layered AdS/CFT-type dualities.

  13. Phase Transition and Clapeyon Equation of Black Hole in Higher Dimensional AdS Spacetime

    CERN Document Server

    Zhao, Hui-Hua; Ma, Meng-Sen; Zhao, Ren

    2014-01-01

    By Maxwell equal area law we study the phase transition in higher dimensional Anti-de Sitter (AdS) Reissner-Nordstr\\"{o}m (RN) black hole and Kerr black hole in this paper. The coexisting region of the two phases involved in the phase transition is found and the coexisting curves are shown in $P-T$ figures. We also analytically investigate the parameters which affect the coexisting curves. To better compare with ordinary thermodynamic systems, the Clapeyon equation is derived for higher dimensional AdS black holes. This paper can help to deepen the understanding of the phase transition and phase structure of AdS black holes.

  14. Boundary action of free AdS higher-spin gauge fields and the holographic correspondence

    CERN Document Server

    Joung, Euihun

    2011-01-01

    We determine the boundary terms of the free higher-spin action which reproduce the AdS Fronsdal equations in an AdS manifold with a finite distance boundary. The boundary terms are further constrained by the gauge invariance of the total action. We show that, for spins larger than two, no local boundary term can restore the full gauge symmetry, and the broken symmetry corresponds to higher-spin Weyl transformations on the boundary CFT. The boundary action is used for the evaluation of the on-shell higher-spin AdS action in terms of the boundary data given by a conformal higher-spin field.

  15. Geometric Finiteness, Holography and Quasinormal Modes for the Warped AdS_3 Black Hole

    CERN Document Server

    Gupta, Kumar S; Sen, Siddhartha; Sivakumar, M

    2009-01-01

    We show that there exists a precise kinematical notion of holography for the Euclidean warped $AdS_3$ black hole. This follows from the fact that the Euclidean warped $AdS_3$ black hole spacetime is a geometrically finite hyperbolic manifold. For such manifolds a theorem of Sullivan provides a one-to-one correspondence between the hyperbolic structure in the bulk and the conformal structure of its boundary. Using this theorem we obtain the holographic quasinormal modes for the warped $AdS_3$ black hole.

  16. An improved AFS phase for AdS3 string integrability

    CERN Document Server

    Abbott, Michael C

    2015-01-01

    We propose a number of modifications to the classical term in the dressing phase for integrable strings in AdS3 x S3 x S3 x S1, and check these against existing perturbative calculations, crossing symmetry, and the semiclassical limit of the Bethe equations. The principal change is that the phase for different masses should start with a term Q_1 Q_2, like the one-loop AdS3 dressing phase, rather than Q_2 Q_3 as for the original AdS5 AFS phase.

  17. Holographic Complexity and Fidelity Susceptibility as Holographic Information Dual to Different Volumes in AdS

    CERN Document Server

    Mazhari, N S; Bahamonde, Sebastian; Faizal, Mir; Myrzakulov, Ratbay

    2016-01-01

    The holographic complexity and fidelity susceptibility have been defined as new quantities dual to different volumes in AdS. In this paper, we will use these new proposals to calculate both of these quantities for a variety of interesting deformations of AdS. We obtain the holographic complexity and fidelity susceptibility for an AdS black hole, Janus solution and a solution with cylindrically symmetry, an inhomogeneous background and a hyperscaling violating background. It is observed that the holographic complexity depends on the size of the subsystem for all these solutions and the fidelity susceptibility does not any such dependence.

  18. [Rapid analysis of added ingredients in heroin].

    Science.gov (United States)

    Wang, Ji-fen; Yu, Jing; Guo, Xin; Sun, Xing-long; Wang, Ding-fang

    2011-07-01

    The method of rapid analysis of added ingredients in heroin was studied in the present paper. Adding sucrose, fructose, glucose, starch, caffeine and phenacetin to heroin with a certain percentage, the changes in the infrared spectrum with the concentration of heroin increasing and the detection limit of the additives were determined. Whether or not heroin can be detected in the sample with high concentration of added ingredients was studied using Raman spectroscopy. Similarly, in high purity of heroin, whether or not Raman spectroscopy can detect the added ingredients was tested. Through systematic experiments, the results showed that: using infrared spectroscopy and Raman spectroscopy to test the added ingredients of heroin is a rapid and effective method. Each has both advantages and disadvantages. We should select the appropriate method according to the actual cases.

  19. The concept of added value of FM

    DEFF Research Database (Denmark)

    2012-01-01

    Purpose: This chapter presents research perspectives and theoretical reflections on the concept of added value of FM from a variety of academic fields. Methodology: A literature review of the most influential journals within the academic fields of Facilities Management (FM), Corporate Real Estate...... conceptualization of the concept of added value of FM is of utmost importance for further research into the added value of FM and well-considered, evidence- based Value Adding Management in practice. Research limitations: Due to limited time not all FM-related journals could be included in the literature review...... Management (CREM) and Business to Business Marketing (B2B Marketing). Findings: The research shows different definitions and focus points, dependent on the academic field and the area of application. The different research perspectives explored a holistic view on the added value of FM by the integration...

  20. Inflation in AdS/CFT

    Energy Technology Data Exchange (ETDEWEB)

    Freivogel, Ben; /Stanford U., Phys. Dept. /LBL, Berkeley; Hubeny, Veronika E.; /LBL, Berkeley /Durham U., Dept. of Math.; Maloney, Alexander; /Stanford U., Phys. Dept.; Myers, Rob; /Perimeter Inst. Theor. Phys. /Waterloo U.; Rangamani, Mukund; /LBL, Berkeley /Durham U., Dept. of Math.; Shenker, Stephen; /Stanford U., Phys. Dept.

    2005-10-07

    We study the realization of inflation within the AdS/CFT correspondence. We assume the existence of a string landscape containing at least one stable AdS vacuum and a (nearby) metastable de Sitter state. Standard arguments imply that the bulk physics in the vicinity of the AdS minimum is described by a boundary CFT. We argue that large enough bubbles of the dS phase, including those able to inflate, are described by mixed states in the CFT. Inflating degrees of freedom are traced over and do not appear explicitly in the boundary description. They nevertheless leave a distinct imprint on the mixed state. Analytic continuation allows us, in principle, to recover a large amount of nonperturbatively defined information about the inflating regime. Our work also shows that no scattering process can create an inflating region, even by quantum tunneling, since a pure state can never evolve into a mixed state under unitary evolution.We study the realization of inflation within the AdS/CFT correspondence. We assume the existence of a string landscape containing at least one stable AdS vacuum and a (nearby) metastable de Sitter state. Standard arguments imply that the bulk physics in the vicinity of the AdS minimum is described by a boundary CFT. We argue that large enough bubbles of the dS phase, including those able to inflate, are described by mixed states in the CFT. Inflating degrees of freedom are traced over and do not appear explicitly in the boundary description. They nevertheless leave a distinct imprint on the mixed state. Analytic continuation allows us, in principle, to recover a large amount of nonperturbatively defined information about the inflating regime. Our work also shows that no scattering process can create an inflating region, even by quantum tunneling, since a pure state can never evolve into a mixed state under unitary evolution.

  1. A Grassmann Path From AdS$_3$ to Flat Space

    CERN Document Server

    Krishnan, Chethan; Roy, Shubho

    2013-01-01

    We show that interpreting the inverse AdS$_3$ radius $1/l$ as a Grassmann variable results in a formal map from gravity in AdS$_3$ to gravity in flat space. The underlying reason for this is the fact that $ISO(2,1)$ is the Inonu-Wigner contraction of $SO(2,2)$. We show how this works for the Chern-Simons actions, demonstrate how the general (Banados) solution in AdS$_3$ maps to the general flat space solution, and how the Killing vectors, charges and the Virasoro algebra in the Brown-Henneaux case map to the corresponding quantities in the BMS$_3$ case. Our results straightforwardly generalize to the higher spin case: the recently constructed flat space higher spin theories emerge automatically in this approach from their AdS counterparts. We conclude with a discussion of singularity resolution in the BMS gauge as an application.

  2. Quantum corrections to supergravity on AdS2×S2

    Science.gov (United States)

    Larsen, Finn; Lisbão, Pedro

    2015-04-01

    We compute the off-shell spectrum of supergravity on AdS2×S2 by explicit diagonalization of the equations of motion for an effective AdS2 theory where all fields are dualized to scalars and spin-1/2 fermions. We classify all bulk modes as physical, gauge violating, and pure gauge then compute the physical spectrum by explicit cancellation of unphysical modes. We identify boundary modes as physical fields on S2 that are formally pure gauge but with gauge function that is non-normalizable on AdS2. As an application we compute the leading quantum correction to AdS2×S2 as a sum over physical fields including boundary states. The result agrees with a previous computation by Sen [1] where unphysical modes were canceled by ghosts.

  3. Impaired cognition in depression and Alzheimer (AD: a gradient from depression to depression in AD

    Directory of Open Access Journals (Sweden)

    Narahyana Bom de Araujo

    2014-09-01

    Full Text Available Objective To assess cognition in major depressed (MD, Alzheimer's disease (AD, and depression in AD elderly. Method Subjects were evaluated by Mini Mental, Rey Auditory Verbal Learning Test, Rey Complex Figure, Digit Span, Similarities, Trail Making A/B, Verbal Fluency and Stroop. One-way ANOVA and multivariate models were used to compare the performance of each group on neuropsychological tests. Results We evaluated 212 subjects. Compared to MD, attention, working memory, processing speed and recall showed significantly better in controls. Controls showed significantly higher performance in all cognitive measures, except in attention compared to AD. Verbal fluency, memory, processing speed and abstract reasoning in MD was significantly higher compared to AD. AD was significantly better in general cognitive state than depression in AD. All other cognitive domains were similar. Conclusion A decreasing gradient in cognition appeared from the control to depression in AD, with MD and AD in an intermediate position.

  4. Study of ADS-B Data Evaluation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun; LIU Wei; ZHU Yanbo

    2011-01-01

    In western China,the terrain and meteorological conditions are so complex that it is not suitable to construct new radar stations.Automatic dependent surveillance-broadcast(ADS-B) is a totally new surveillance method,so before practically applied and operated in China,abundant tests and evaluations are necessary to validate the performance of ADS-B and guarantee the operational security.During the flight tests,we collect the data of radar,ADS-B and high accuracy position and compare the performance of ADS-B with radar based on high accuracy position.To solve the asynchronous problem among radar data,ADS-B data and real-time kinematic(RTK) data caused by different update rates,this article proposes the technique of synchronizing multi-surveil- lance data by extrapolating from the data of low update rate to high update rate according to velocity and heading.Meanwhile,because radar data,ADS-B data and RTK data are expressed in different coordinates and cannot be compared each other,this article provides a method to unifying the coordinates of multi-surveillance data.By the analysis and evaluation,we can conclude that the performance of ADS-B is better than radar.

  5. Supergravity background of the lambda-deformed AdS_3 x S^3 supercoset

    CERN Document Server

    Chervonyi, Yuri

    2016-01-01

    We construct the solution of type IIB supergravity describing the integrable lambda-deformation of the AdS_3 x S^3 supercoset. While the geometry corresponding to the deformation of the bosonic coset has been found in the past, our background is more natural for studying superstrings, and several interesting features distinguish our solution from its bosonic counterpart. We also report progress towards constructing the lambda-deformation of the AdS_5 x S^5 supercoset.

  6. Ad Hoc Network Securing Policy%Ad hoc网络安全策略

    Institute of Scientific and Technical Information of China (English)

    刘志远; 张曼曼

    2006-01-01

    本文首先介绍了Ad hoc网络的产生、定义、特点和应用,然后在探讨Ad hoc网络的安全需求的基础上,着重分析了移动Ad hoc网络易于遭受的攻击,最后讨论并提出了Ad Hoc网络的一些安全策略.

  7. Yangian of AdS_3/CFT_2 and its deformation

    CERN Document Server

    Regelskis, Vidas

    2015-01-01

    We construct highest-weight modules and a Yangian extension of the centrally extended superalgebra appearing in the worldsheet scattering associated with the AdS_3 /CFT_2 duality, and show a link to the Yangian of AdS_5/CFT_4. We also consider a quantum deformation of this superalgebra, its modules and a quantum affine extension of the Drinfeld-Jimbo type which describes deformed worldsheet scattering.

  8. Half BPS states in AdS_5 x Y^{p,q}

    CERN Document Server

    Gava, Edi; Milanesi, Giuseppe; O'Loughlin, Martin

    2008-01-01

    We study a class of solutions of IIB Supergravity which are asymptotically AdS_5 x Y^{p,q}. They have an R x SO(4) x SU(2) x U(1) isometry and preserve half of the 8 supercharges of the background geometry. They are described by a set of second order differential equations that we have found and analysed in a previous paper, where we studied 1/8 BPS states in the maximally supersymmetric AdS_5 x S^5 background. These geometries correspond to certain chiral primary operators of the N=1 superconformal quiver theories, dual to IIB theory on AdS_5 x Y^{p,q}. We also show how to recover the AdS_5 x Y^{p,q} backgrounds by suitably doubling the number of preserved supersymmetries. We then solve the differential equations perturbatively in a large AdS_5 radius expansion, imposing asymptotic AdS_5 x Y^{p,q} boundary conditions. We compute the global baryonic and mesonic charges, including the R-charge. As for the computation of the mass, i.e. the conformal dimension D of the dual field theory operators, which is notor...

  9. Service placement in ad hoc networks

    CERN Document Server

    Wittenburg, Georg

    2012-01-01

    Service provisioning in ad hoc networks is challenging given the difficulties of communicating over a wireless channel and the potential heterogeneity and mobility of the devices that form the network. Service placement is the process of selecting an optimal set of nodes to host the implementation of a service in light of a given service demand and network topology. The key advantage of active service placement in ad hoc networks is that it allows for the service configuration to be adapted continuously at run time. ""Service Placement in Ad Hoc Networks"" proposes the SPi service placement fr

  10. Value added meat marketing around the globe

    DEFF Research Database (Denmark)

    Grebitus, Carola; Mueller Loose, Simone

    In highly competitive meat markets it is important to offer value added products to consumers. Thus, we need to understand which attributes are especially valued by consumers. This track session will contribute to a better understanding of consumer preferences for value added meats across different...... countries and simultaneously address different stages of the food chain by acknowledging factors such as breeding, forage (fat content), meat cuts as well as product labelling and packaging. Comparing consumers’ choices for value added pork and beef across different countries is the main theme and focus...

  11. Trust Based Routing in Ad Hoc Network

    Science.gov (United States)

    Talati, Mikita V.; Valiveti, Sharada; Kotecha, K.

    Ad Hoc network often termed as an infrastructure-less, self- organized or spontaneous network.The execution and survival of an ad-hoc network is solely dependent upon the cooperative and trusting nature of its nodes. However, this naive dependency on intermediate nodes makes the ad-hoc network vulnerable to passive and active attacks by malicious nodes and cause inflict severe damage. A number of protocols have been developed to secure ad-hoc networks using cryptographic schemes, but all rely on the presence of trust authority. Due to mobility of nodes and limitation of resources in wireless network one interesting research area in MANET is routing. This paper offers various trust models and trust based routing protocols to improve the trustworthiness of the neighborhood.Thus it helps in selecting the most secure and trustworthy route from the available ones for the data transfer.

  12. Introduction to AdS-CFT

    CERN Document Server

    Nastase, Horatiu

    2007-01-01

    These lectures present an introduction to AdS-CFT, and are intended both for begining and more advanced graduate students, which are familiar with quantum field theory and have a working knowledge of their basic methods. Familiarity with supersymmetry, general relativity and string theory is helpful, but not necessary, as the course intends to be as self-contained as possible. I will introduce the needed elements of field and gauge theory, general relativity, supersymmetry, supergravity, strings and conformal field theory. Then I describe the basic AdS-CFT scenario, of ${\\cal N}=4 $ Super Yang-Mills's relation to string theory in $AdS_5\\times S_5$, and applications that can be derived from it: 3-point functions, quark-antiquark potential, finite temperature and scattering processes, the pp wave correspondence and spin chains. I also describe some general properties of gravity duals of gauge theories.

  13. Heat kernels on cone of AdS2 and k-wound circular Wilson loop in AdS5 × S5 superstring

    Science.gov (United States)

    Bergamin, R.; Tseytlin, A. A.

    2016-04-01

    We compute the one-loop world-sheet correction to partition function of {{AdS}}5× {{{S}}}5 superstring that should be representing k-fundamental circular Wilson loop in planar limit. The 2d metric of the minimal surface ending on k-wound circle at the boundary is that of a cone of AdS2 with deficit 2π (1-k). We compute the determinants of 2d fluctuation operators by first constructing heat kernels of scalar and spinor Laplacians on the cone using the Sommerfeld formula. The final expression for the k-dependent part of the one-loop correction has simple integral representation but is different from earlier results.

  14. Profiling value added position in FM

    DEFF Research Database (Denmark)

    Katchamart, Akarapong

    organizations can best add value. Based on comprehensive literature studies and 7 case studies of private and public organisations from Denmark, Holland, Hong Kong and Thailand, the dissertation analyses, how FM organizations can best create added value. From the analyses the following four value added...... - FM organizations influence the business productivities and outcome Each type of value added requires specific conditions and contingencies involved. This research thus offers a visual aid tool, “FM product-process matrix”, to assist practitioners to indicate their existing circumstances and contexts...... the unarticulated notions of added value from FM organization and activities. It will broaden the managerial perception and discussion on FM provision ´s abilities and capabilities. The results are besides the field of FM also of relevance for management of other service industries and functions....

  15. Microbial production of value-added nutraceuticals.

    Science.gov (United States)

    Wang, Jian; Guleria, Sanjay; Koffas, Mattheos A G; Yan, Yajun

    2016-02-01

    Nutraceuticals are important natural bioactive compounds that confer health-promoting and medical benefits to humans. Globally growing demands for value-added nutraceuticals for prevention and treatment of human diseases have rendered nutraceuticals a multi-billion dollar market. However, supply limitations and extraction difficulties from natural sources such as plants, animals or fungi, restrict the large-scale use of nutraceuticals. Metabolic engineering via microbial production platforms has been advanced as an eco-friendly alternative approach for production of value-added nutraceuticals from simple carbon sources. Microbial platforms like the most widely used Escherichia coli and Saccharomyces cerevisiae have been engineered as versatile cell factories for production of diverse and complex value-added chemicals such as phytochemicals, prebiotics, polysaccaharides and poly amino acids. This review highlights the recent progresses in biological production of value-added nutraceuticals via metabolic engineering approaches.

  16. Heat kernels on cone of $AdS_2$ and $k$-wound circular Wilson loop in $AdS_5 \\times S^5$ superstring

    CERN Document Server

    Bergamin, R

    2015-01-01

    We compute the one-loop world-sheet correction to partition function of $AdS_5 \\times S^5$ superstring that should be representing $k$-fundamental circular Wilson loop in planar limit. The 2d metric of the minimal surface ending on $k$-wound circle at the boundary is that of a cone of $AdS_2$ with deficit $2\\pi (1-k)$. We compute determinants of 2d fluctuation operators by first constructing heat kernels of scalar and spinor Laplacians on the cone using the Sommerfeld formula. The final expression for the k-dependent part of the one-loop correction has simple integral representation but is different from earlier results.

  17. Multilevel security model for ad hoc networks

    Institute of Scientific and Technical Information of China (English)

    Wang Changda; Ju Shiguang

    2008-01-01

    Modern battlefield doctrine is based on mobility, flexibility, and rapid response to changing situations.As is well known, mobile ad hoc network systems are among the best utilities for battlefield activity. Although much research has been done on secure routing, security issues have largely been ignored in applying mobile ad hoc network theory to computer technology. An ad hoc network is usually assumed to be homogeneous, which is an irrational assumption for armies. It is clear that soldiers, commanders, and commanders-in-chief should have different security levels and computation powers as they have access to asymmetric resources. Imitating basic military rank levels in battlefield situations, how multilevel security can be introduced into ad hoc networks is indicated, thereby controlling restricted classified information flows among nodes that have different security levels.

  18. The Tetrahedral Zamolodchikov Algebra and the {AdS_5× S^5} S-matrix

    Science.gov (United States)

    Mitev, Vladimir; Staudacher, Matthias; Tsuboi, Zengo

    2017-08-01

    The S-matrix of the {AdS_5× S^5} string theory is a tensor product of two centrally extended su{(2|2)\\ltimes R^2 S-matrices, each of which is related to the R-matrix of the Hubbard model. The R-matrix of the Hubbard model was first found by Shastry, who ingeniously exploited the fact that, for zero coupling, the Hubbard model can be decomposed into two XX models. In this article, we review and clarify this construction from the AdS/CFT perspective and investigate the implications this has for the {AdS_5× S^5} S-matrix.

  19. The Tetrahedron Zamolodchikov Algebra and the AdS5 x S5 S-matrix

    CERN Document Server

    Mitev, Vladimir; Tsuboi, Zengo

    2012-01-01

    The S-matrix of the AdS5 x S5 string theory is a tensor product of two centrally extended su(2|2) S-matrices, each of which is related to the R-matrix of the Hubbard model. The R-matrix of the Hubbard model was first found by Shastry, who ingeniously exploited the fact that, for zero coupling, the Hubbard model can be decomposed into two XX models. In this article, we review and clarify this construction from the AdS/CFT perspective and investigate the implications this has for the AdS5 x S5 S-matrix.

  20. Adding stress plot function to NASTRAN

    Science.gov (United States)

    Katoh, S.

    1978-01-01

    Stress plot function was developed and added to the NASTRAN level 15.5. Computed stress distribution can be displayed by this function, with vectors showing the principal stresses of the finite elements over the specified portions of the structure. NASTRAN is reviewed in the aspect of plotting capabilities. Stress tensor field is examined in preparation of stress display. Then the stress plot function as added to the NASTRAN is described. A sample plotout by this function is shown.

  1. Evaluation of co-added astronomical images

    Science.gov (United States)

    Nasyrova, M.; Vítek, S.

    2017-07-01

    The co-adding, averaging, or stacking of data are popular techniques to improve scientific outcomes in astronomy, especially in the case of extraction of very faint sources. These methods allow to increase the signal-to-noise ratio and to decrease the point spread function width, which improves the accuracy of segmentation. This paper deals with a brief review of image co-adding algorithms and their evaluation regarding improving the qualitative parameters of the image data.

  2. AdS-Sliced Flavor Branes and Adding Flavor to the Janus Solution

    CERN Document Server

    Clark, Adam B; Newman, George M; Rommal, Andrea

    2014-01-01

    We implement D7 flavor branes in AdS-sliced coordinates on $AdS_5\\times S^5$ with the ansatz that the brane fluctuates only in the warped ($\\mu$) direction in this slicing, which is particularly appropriate for studying the Janus solution. The natural field theory dual in this slicing is $\\mathcal{N}=4$ super Yang-Mills on two copies of $AdS_4$. Branes extending from $\\mu=\\pm\\pi/2$ can end at different locations, giving rise to quarks with piecewise constant mass on each $AdS_4$ half-space, jumping discontinuously between them. A second class of flavor brane solutions exists in this coordinate system, dubbed "continuous" flavor branes, that extend across the entire range of $\\mu$. We propose that the correct dual interpretation of "disconnected" flavor brane in this ansatz is a quark hypermultiplet with constant mass on one of the AdS$_4$ half-spaces with totally reflecting boundary conditions at the boundary of AdS$_4$; whereas the dual interpretation of a continuous flavor brane has totally transparent boun...

  3. Integrable strings for AdS/CFT

    CERN Document Server

    Borsato, Riccardo

    2016-01-01

    In this PhD thesis we review some aspects of integrable models related to string backgrounds or their deformations. In the first part we develop methods to obtain exact results in the AdS3/CFT2 correspondence. We consider the AdS_3 x S^3 x T^4 background with pure Ramond-Ramond flux and we find the all-loop worldsheet S-matrix by exploiting the symmetries of the model in light-cone gauge. As we naturally include the massless modes on the worldsheet, we derive the full set of Bethe-Yang equations. In the massive sector we give also a spin-chain description and we write down solutions compatible with crossing for the scalar factors which are not constrained by simmetries. In the second part of the thesis we consider the so-called "eta-deformation" of the superstring on AdS_5 x S^5. We first discuss the effects of the deformation at the level of the bosonic sigma-model, and we match the tree-level worldsheet scattering processes to the expansion of the q-deformed S-matrix. To identify the missing Ramond-Ramond f...

  4. Brick Walls and AdS/CFT

    CERN Document Server

    Kay, Bernard S

    2011-01-01

    We discuss the relationship between the bulk-boundary correspondence in Rehren's algebraic holography (and in other 'fixed-background' approaches to holography) and in mainstream 'Maldacena AdS/CFT'. Especially, we contrast the understanding of black-hole entropy from the viewpoint of QFT in curved spacetime -- in the framework of 't Hooft's 'brick wall' model -- with the understanding based on Maldacena AdS/CFT. We show that the brick-wall modification of a Klein Gordon field in the Hartle-Hawking-Israel state on 1+2-Schwarzschild AdS (BTZ) has a well-defined boundary limit with the same temperature and entropy as the brick-wall-modified bulk theory. One of our main purposes is to point out a close connection, for general AdS/CFT situations, between the puzzle raised by Arnsdorf and Smolin regarding the relationship between Rehren's algebraic holography and mainstream AdS/CFT and the puzzle embodied in the 'correspondence principle' proposed by Mukohyama and Israel in their work on the brick-wall approach to...

  5. Gauge Symmetries and Holographic Anomalies of Chern-Simons and Transgression AdS Gravity

    CERN Document Server

    Mora, Pablo

    2014-01-01

    We review the issue of gauge and gravitational anomalies with backgrounds, maybe offering a new outlook on some aspects of these questions. We compute the holographic anomalies of hypothetical theories dual, in the sense of the AdS-CFT correspondence, to Chern-Simons AdS gravities. Those anomalies are either gauge anomalies associated to the AdS gauge group of the theory or diffeomorphism anomalies, with each kind related to the other. As a result of using suitable action principles por Chern-Simons AdS gravities, coming from Transgression forms, we obtain finite results without the need for further regularization. Our results are of potential interest for Lovelock gravity theories, as it has been shown that the boundary terms dictated by the transgressions for Chern-Simons gravities are also suitable to regularize Lovelock theories. The Wess-Zumino consistency condition ensures that anomalies of the generic form computed here should appear for these and other theories.

  6. AdS5×S(5) mirror model as a string sigma model.

    Science.gov (United States)

    Arutyunov, Gleb; van Tongeren, Stijn J

    2014-12-31

    Doing a double Wick rotation in the world sheet theory of the light cone AdS5×S(5) superstring results in an inequivalent, so-called mirror theory that plays a central role in the field of integrability in the AdS-CFT correspondence. We show that this mirror theory can be interpreted as the light cone theory of a free string on a different background. This background is related to dS5×H(5) by a double T-duality, and has hidden supersymmetry. The geometry can also be extracted from an integrable deformation of the AdS5×S(5) sigma model, and we prove the observed mirror duality of these deformed models at the bosonic level as a byproduct. While we focus on AdS5×S(5), our results apply more generally.

  7. On Thermodynamics of AdS Black Holes in M-Theory

    CERN Document Server

    Belhaj, A; Moumni, H EL; Masmar, K; Sedra, M B

    2015-01-01

    Motivated by a recent work on asymptotically AdS_4 black holes in M-theory, we investigate the thermodynamics and thermodynamical geometry of AdS black holes from M2 and M5-branes. Concretely, we consider AdS black holes in AdS_{p+2}\\times S^{11-p-2}, where p=2,5 by interpreting the number of M2 (and M5-branes) as a thermodynamical variable. We study the corresponding phase transition to examine their stabilities by calculating and discussing various thermodynamical quantities including the chemical potential. Then, we compute the thermodynamical curvatures from the Quevedo metric for M2 and M5-branes geometries to reconsider the stability of such black objects. The Quevedo metric singularities recover similar stability results provided by the phase transition program.

  8. Higher spin contributions to holographic fluid dynamics in AdS5/CFT4

    Science.gov (United States)

    Lee, Seungjin; Polyakov, Dimitri

    2014-08-01

    We calculate the graviton's β function in the AdS string-theoretic sigma model, perturbed by vertex operators for Vasiliev's higher spin gauge fields in AdS5. The result is given by βmn=Rmn+4Tmn(g ,u) (with the AdS radius set to 1 and the graviton polarized along the AdS5 boundary), with the matter stress-energy tensor given by that of conformal holographic fluid in d =4, evaluated at the temperature given by T =1/π. The stress-energy tensor is given by Tmn=gmn+4umun+∑NTmn(N) where u is the vector excitation satisfying u2=-1 and N is the order of the gradient expansion in the dissipative part of the tensor. We calculate the contributions up to N =2. The higher spin excitations contribute to the β function, ensuring the overall Weyl covariance of the matter stress tensor. We conjecture that the structure of gradient expansion in d =4 conformal hydrodynamics at higher orders is controlled by the higher spin operator algebra in AdS5.

  9. Interpolating from Bianchi Attractors to Lifshitz and AdS Spacetimes

    CERN Document Server

    Kachru, Shamit; Saha, Arpan; Samanta, Rickmoy; Trivedi, Sandip P

    2013-01-01

    We construct classes of smooth metrics which interpolate from Bianchi attractor geometries of Types II, III, VI and IX in the IR to Lifshitz or $AdS_2 \\times S^3$ geometries in the UV. While we do not obtain these metrics as solutions of Einstein gravity coupled to a simple matter field theory, we show that the matter sector stress-energy required to support these geometries (via the Einstein equations) does satisfy the weak, and therefore also the null, energy condition. Since Lifshitz or $AdS_2 \\times S^3$ geometries can in turn be connected to $AdS_5$ spacetime, our results show that there is no barrier, at least at the level of the energy conditions, for solutions to arise connecting these Bianchi attractor geometries to $AdS_5$ spacetime. The asymptotic $AdS_5$ spacetime has no non-normalizable metric deformation turned on, which suggests that furthermore, the Bianchi attractor geometries can be the IR geometries dual to field theories living in flat space, with the breaking of symmetries being either sp...

  10. Closed string tachyons on AdS orbifolds and dual Yang-Mills instantons

    Energy Technology Data Exchange (ETDEWEB)

    Hikida, Y. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Iizuka, N. [California Univ., Santa Barbara, CA (United States). Kavli Inst. for Theoretical Physics

    2007-06-15

    We study the condensation of localized closed string tachyons on AdS orbifolds both from the bulk and boundary theory viewpoints. We first extend the known results for AdS{sub 5}/Z{sub k} to AdS{sub 3}/Z{sub k} case, and we proposed that the AdS{sub 3}/Z{sub k} decays into AdS{sub 3}/Z{sub k'} with k{sup '} < k. From the bulk viewpoint, we obtain a time-dependent gravity solution describing the decay of AdS orbifold numerically. From the dual gauge theory viewpoint, we calculated the Casimir energies of gauge theory vacua and it is found that their values are exactly the same as the masses of dual geometries, even though they are in different parameter regimes of 't Hooft coupling. We also consider AdS{sub 5} orbifold. The decay of AdS{sub 5}/Z{sub k} is dual to the transition between the vacua of dual gauge theory on R{sub t} x S{sup 3}/Z{sub k}. We constructed the instanton solutions describing the transitions by making use of instanton solutions on R{sub t} x S{sup 2}. (orig.)

  11. Implementation of Recursion Relations in Gluon Scattering Amplitude Calculations in AdS4 /CFT3

    Science.gov (United States)

    Dokmetzoglou, Nikolaos; Kharel, Savan

    2017-01-01

    The Anti-de Sitter/Conformal Field Theory (AdS/CFT) correspondence is a duality between a theory of gravity in curved-space (AdS) and a conformally-invariant quantum field theory in flat-space (CFT). Scattering amplitudes are observables associated with the probability of the interaction of a given assembly of particles. Gluons, being the exchange particles associated with the strong nuclear force, which holds quarks together to form protons, are abundant byproducts of fundamental particle collisions. Thus, studying gluon scattering amplitudes is an effective way of deepening our understanding of these observables in AdS/CFT. Traditionally, Feynman diagrams have been used to calculate such scattering amplitudes. In this project, we use factorization properties and recursion relations to simplify these calculations. More specifically, we calculate multiple (different helicity combinations) four-point gluon scattering amplitudes in AdS4 /CFT3 (4-D AdS and 3-D CFT) as sums of products of three-point amplitudes. And then we calculate a five-point gluon scattering amplitude in AdS4 /CFT3 by decomposing it into a sum of products of these four-point and three-point amplitudes. Finally we comment on useful identities for checking these amplitudes. This work was supported by a Weinstein Davidson College Research Initiative Summer Research grant.

  12. Extended supersymmetric sigma models in AdS_4 from projective superspace

    CERN Document Server

    Butter, Daniel; Lindstrom, Ulf; Tartaglino-Mazzucchelli, Gabriele

    2012-01-01

    There exist two superspace approaches to describe N=2 supersymmetric nonlinear sigma models in four-dimensional anti-de Sitter (AdS_4) space: (i) in terms of N=1 AdS chiral superfields, as developed in arXiv:1105.3111 and arXiv:1108.5290; and (ii) in terms of N=2 polar supermultiplets using the AdS projective-superspace techniques developed in arXiv:0807.3368. The virtue of the approach (i) is that it makes manifest the geometric properties of the N=2 supersymmetric sigma-models in AdS_4. The target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations on the two-sphere of complex structures. The power of the approach (ii) is that it allows us, in principle, to generate hyperkahler metrics as well as to address the problem of deformations of such metrics. Here we show how to relate the formulation (ii) to (i) by integrating out an infinite number of N=1 AdS auxiliary superfields and performing a superfield duality transformation. We al...

  13. AdS and Lifshitz scalar hairy black holes in Gauss-Bonnet gravity

    Science.gov (United States)

    Chen, Bin; Fan, Zhong-Ying; Zhu, Lu-Yao

    2016-09-01

    We consider Gauss-Bonnet (GB) gravity in general dimensions, which is nonminimally coupled to a scalar field. By choosing a scalar potential of the type V (ϕ )=2 Λ0+1/2 m2ϕ2+γ4ϕ4 , we first obtain large classes of scalar hairy black holes with spherical/hyperbolic/planar topologies that are asymptotic to locally anti- de Sitter (AdS) space-times. We derive the first law of black hole thermodynamics using Wald formalism. In particular, for one class of the solutions, the scalar hair forms a thermodynamic conjugate with the graviton and nontrivially contributes to the thermodynamical first law. We observe that except for one class of the planar black holes, all these solutions are constructed at the critical point of GB gravity where there exist unique AdS vacua. In fact, a Lifshitz vacuum is also allowed at the critical point. We then construct many new classes of neutral and charged Lifshitz black hole solutions for an either minimally or nonminimally coupled scalar and derive the thermodynamical first laws. We also obtain new classes of exact dynamical AdS and Lifshitz solutions which describe radiating white holes. The solutions eventually become AdS or Lifshitz vacua at late retarded times. However, for one class of the solutions, the final state is an AdS space-time with a globally naked singularity.

  14. The Impact of Ad Characteristics on Adolescents’ Attitudes Towards Antismoking Ads

    Directory of Open Access Journals (Sweden)

    Domen Bajde

    2008-03-01

    Full Text Available Smoking exerts a considerable burden not only on those who smoke but just as well on society at large. In response, governments and institutions often resort to advertising which aims to discourage smoking. Unfortunately, our knowledge of the workings of antismoking advertising is detrimentally limited. In particular, the literature delving into the impact of antismoking ad characteristics (e. g., ad content, valence, intensity on the overall effectiveness of antismoking advertising is scarce and contradictory. This empirical study aims to enhance the knowledge of antismoking advertising by presenting results of the survey involving Slovene adolescents. The adolescents were first exposed to advertisements of different antismoking ad contents (for the purpose of this study the term ‘ad content’ refers to types of appeals used in antismoking advertising, ad valence and intensity, and later invited to respond to a number of questions measuring their attitudes toward the ads, their attitudes toward smoking, their intentions to smoke, etc. The results indicate that while the different intensity and valence of ads produce varying attitudes toward the ads, we could not confirm these differences based on ad content. Also, we found that adolescent smokers respond to antismoking ads differently than do their nonsmoking peers. Our findings offer several important implications for antismoking advertisers and the research community interested in the workings of antismoking advertising.

  15. On the Thermodynamic Geometry and Critical Phenomena of AdS Black Holes

    CERN Document Server

    Sahay, Anurag; Sengupta, Gautam

    2010-01-01

    In this paper, we study various aspects of the equilibrium thermodynamic state space geometry of AdS black holes. We first examine the Reissner-Nordstrom-AdS (RN-AdS) and the Kerr-AdS black holes. In this context, the state space scalar curvature of these black holes are analysed in various regions of their thermodynamic parameter space. This provides important new insights into the structure and significance of the scalar curvature. We further investigate critical phenomena, and the behaviour of the scalar curvature near criticality, for KN-AdS black holes in two mixed ensembles, introduced and elucidated in our earlier work arXiv:1002.2538 [hep-th]. The critical exponents are identical to those in the RN-AdS and Kerr-AdS cases in the canonical ensemble. This suggests an universality in the scaling behaviour near critical points of AdS black holes. Our results further highlight qualitative differences in the thermodynamic state space geometry for electric charge and angular momentum fluctuations of these.

  16. Comment on "AdS nonlinear instability: moving beyond spherical symmetry" [Class. Quantum Grav. 33 23LT01 (2016)

    CERN Document Server

    Rostworowski, Andrzej

    2016-01-01

    We argue that if the degeneracy of the spectrum of linear perturbations of AdS is properly taken into account, there are globally regular, time-periodic, asymptotically AdS solutions (geons) bifurcating from each linear eigenfrequency of AdS.

  17. Brick walls and AdS/CFT

    Science.gov (United States)

    Kay, Bernard S.; Ortíz, L.

    2014-05-01

    We discuss the relationship between the bulk-boundary correspondence in Rehren's algebraic holography (and in other `fixed-background', QFT-based, approaches to holography) and in mainstream string-theoretic `Maldacena AdS/CFT'. Especially, we contrast the understanding of black-hole entropy from the point of view of QFT in curved spacetime—in the framework of 't Hooft's `brick wall' model—with the understanding based on Maldacena AdS/CFT. We show that the brick-wall modification of a Klein-Gordon field in the Hartle-Hawking-Israel state on dimensional Schwarzschild AdS has a well-defined boundary limit with the same temperature and entropy as the brick-wall-modified bulk theory. One of our main purposes is to point out a close connection, for general AdS/CFT situations, between the puzzle raised by Arnsdorf and Smolin regarding the relationship between Rehren's algebraic holography and mainstream AdS/CFT and the puzzle embodied in the `complementarity principle' proposed by Mukohyama and Israel in their work on the brick-wall approach to black hole entropy. Working on the assumption that similar results will hold for bulk QFT other than the Klein-Gordon field and for Schwarzschild AdS in other dimensions, and recalling the first author's proposed resolution to the Mukohyama-Israel puzzle based on his `matter-gravity entanglement hypothesis', we argue that, in Maldacena AdS/CFT, the algebra of the boundary CFT is isomorphic only to a proper subalgebra of the bulk algebra, albeit (at non-zero temperature) the (GNS) Hilbert spaces of bulk and boundary theories are still the `same'—the total bulk state being pure, while the boundary state is mixed (thermal). We also argue from the finiteness of its boundary (and hence, on our assumptions, also bulk) entropy at finite temperature, that the Rehren dual of the Maldacena boundary CFT cannot itself be a QFT and must, instead, presumably be something like a string theory.

  18. Ad Hoc Access Gateway Selection Algorithm

    Science.gov (United States)

    Jie, Liu

    With the continuous development of mobile communication technology, Ad Hoc access network has become a hot research, Ad Hoc access network nodes can be used to expand capacity of multi-hop communication range of mobile communication system, even business adjacent to the community, improve edge data rates. For mobile nodes in Ad Hoc network to internet, internet communications in the peer nodes must be achieved through the gateway. Therefore, the key Ad Hoc Access Networks will focus on the discovery gateway, as well as gateway selection in the case of multi-gateway and handover problems between different gateways. This paper considers the mobile node and the gateway, based on the average number of hops from an average access time and the stability of routes, improved gateway selection algorithm were proposed. An improved gateway selection algorithm, which mainly considers the algorithm can improve the access time of Ad Hoc nodes and the continuity of communication between the gateways, were proposed. This can improve the quality of communication across the network.

  19. Higher spin holography and the AdS string sigma model

    Science.gov (United States)

    Polyakov, Dimitri

    2013-05-01

    We analyse the cubic spin-3 interaction in AdS space using the higher spin extension of the string-theoretic sigma-model constructed in our previous work, whose low energy limit is described by the AdS vacuum solution. We find that, in the leading order of the cosmological constant, the spin-3 correlator on the AdS4 string theory side reproduces the structure of the three-point function of composite operators, quadratic in free fields, in the dual d = 3 vector model. The cancellation of holography violating terms in d = 3 is related to the value of the Liouville background charge in d = 4. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Higher spin theories and holography’.

  20. Vacuum type space-like string surfaces in AdS_3 x S^3

    CERN Document Server

    Dorn, Harald; Kalousios, Chrysostomos; Megrelidze, Luka; Wuttke, Sebastian

    2010-01-01

    We construct and classify all space-like minimal surfaces in AdS_3 x S^3 which globally admit coordinates with constant induced metric on both factors. Up to O(2,2) x O(4) transformations all these surfaces, except one class, are parameterized by four real parameters. The classes of surfaces correspond to different regions in this parameter space and show quite different boundary behavior. Our analysis uses a direct construction of the string coordinates via a group theoretical treatment based on the map of AdS_3 x S^3 to SL(2,R) x SU(2). This is complemented by a cross check via standard Pohlmeyer reduction. After embedding in AdS_5 x S^5 we calculate the regularized area for solutions with a boundary spanned by a four point scattering s-channel momenta configuration.

  1. A note on vectorial AdS5/CFT4 duality for spin- j boundary theory

    Science.gov (United States)

    Bae, Jin-Beom; Joung, Euihun; Lal, Shailesh

    2016-12-01

    The vectorial holographic correspondences between higher-spin theories in AdS5 and free vector models on the boundary are extended to the cases where the latter is described by free massless spin- j field. The dual higher-spin theory in the bulk does not include gravity and can only be defined on rigid AdS5 background with S 4 boundary. We discuss various properties of these rather special higher-spin theories and calculate their one-loop free energies. We show that the result is proportional to the same quantity for spin- j doubleton treated as if it is a AdS5 field. Finally, we consider even more special case where the boundary theory itself is given by an infinite tower of massless higher-spin fields.

  2. Vacuum energy in Einstein-Gauss-Bonnet AdS gravity

    CERN Document Server

    Kofinas, G; Kofinas, Georgios; Olea, Rodrigo

    2006-01-01

    A finite action principle for Einstein-Gauss-Bonnet AdS gravity is presented. The boundary term, which is different for even and odd dimensions, is a functional of the boundary metric, intrinsic curvature and extrinsic curvature. For even dimensions, the boundary term corresponds to the maximal Chern form of the spacetime, and the asymptotic AdS condition for the curvature suffices for the well-posedness of this action. For odd dimensions, the action is stationary under a boundary condition on the variation of the extrinsic curvature. The background-independent Noether charges associated to asymptotic symmetries are found and the Euclidean continuation of the action correctly describes the black hole thermodynamics in the canonical ensemble. In particular, this procedure leads to a covariant formula for the vacuum energy in odd-dimensional asymptotically AdS spacetimes.

  3. A Stochasticity Threshold in Holography and and the Instability of AdS

    CERN Document Server

    Basu, Pallab; Saurabh, Ayush

    2014-01-01

    We give strong numerical evidence that a self-interacting probe scalar field in AdS, with only a few modes turned on initially, will undergo fast thermalization only if it is above a certain energetic threshold. Below the threshold the energy stays close to constant in a few modes for a very long time instead of cascading quickly. This indicates the existance of a Strong Stochasticity Threshold (SST) in holography. The idea of SST is familiar from certain statistical mechanical systems, and we suggest that it exists also in AdS gravity. This would naturally reconcile the generic non-linear instability of AdS observed by Bizon and Rostworowski, with the Fermi-Pasta-Ulam-Tsingou-like quasi-periodocity noticed recently for some classes of initial conditions. We show that our simple set-up captures many of the relevant features of the full gravity-scalar system.

  4. Banados and SUSY: On Supersymmetry and Minimal Surfaces of Locally AdS3 Geometries

    CERN Document Server

    Colgáin, E Ó

    2016-01-01

    We extend the classification of supersymmetric locally AdS$_3$ geometries, beyond BTZ black holes, to the Ba\\~nados geometries, noting that supersymmetries are in one-to-one correspondence with solutions to the Hill differential condition. We show that the number of global supersymmetries is an orbit invariant quantity and identify geometries with zero, one, two, three and four global supersymmetries. As an application of our classification, we exploit supersymmetry, which is preserved locally in the bulk, to determine space-like co-dimension two surfaces in AdS$_3$. In the process, we by-pass geodesics or mappings of AdS$_3$, neither of which have an analogue in higher dimensions, to recover known Hubeny-Rangamani-Takayanagi surfaces. Our findings suggest supersymmetry can be exploited to find extremal surfaces in holographic entanglement entropy.

  5. Quark confinement due to creation of micro AdS black holes in quarkonium model

    CERN Document Server

    Taki, Mehran

    2016-01-01

    We use the solution of the Dirac equation for quarkonium atom in the 4D Anti de sitter (AdS$_{4}$) space to investigate the effect of the large negative cosmological constant on the phenomenon of quark confinement. We do the required calculations in the AdS$_{4}$ space to indicate that large cosmological constant can describe the quark confinement. In fact using the coulomb potential in Dirac equation while we employ the AdS metric will additionally lead us to a linear potential in the quark-antiquark interaction which can be considered to explain the quark confinement. This confining term is arising essentially from the geometrical features of the space. On the other hand the origin of the large cosmological constant can be justified by assuming the appearance of micro black holes in the recent hadronic collision process which is now current, for instance, at the LHC project.

  6. QCD condensates and holographic Wilson loops for asymptotically AdS spaces

    Science.gov (United States)

    Quevedo, R. Carcasses; Goity, J. L.; Trinchero, R. C.

    2014-02-01

    The minimization of the Nambu-Goto action for a surface whose contour defines a circular Wilson loop of radius a placed at a finite value of the coordinate orthogonal to the boundary is considered. This is done for asymptotically anti-de Sitter (AdS) spaces. The condensates of even dimension n =2 through 10 are calculated in terms of the coefficient of an in the expansion of the on-shell subtracted Nambu-Goto action for small a. The subtraction employed is such that it presents no conflict with conformal invariance in the AdS case and need not introduce an additional infrared scale for the case of confining geometries. It is shown that the UV value of the condensates is universal in the sense that they only depend on the first coefficients of the difference with the AdS case.

  7. Photon gas thermodynamics in dS and AdS momentum spaces

    CERN Document Server

    Gorji, M A; Nozari, K; Vakili, B

    2016-01-01

    In this paper, we study thermostatistical properties of a photon gas in the framework of two deformed special relativity models defined by the cosmological coordinatizations of the de Sitter (dS) and anti-de Sitter (AdS) momentum spaces. The dS model is a doubly special relativity theory in which an ultraviolet length scale is invariant under the deformed Lorentz transformations. For the case of AdS model, however, the Lorentz symmetry breaks at the high energy regime. We show that the existence of a maximal momentum in dS momentum space leads to maximal pressure and temperature at the thermodynamical level while maximal internal energy and entropy arise for the case of the AdS momentum space due to the existence of a maximal kinematical energy. These results show the thermodynamical duality of these models much similar to their well-known kinematical duality.

  8. On thermodynamics of AdS black holes in M-theory

    Energy Technology Data Exchange (ETDEWEB)

    Belhaj, A. [Universite Sultan Moulay Slimane, Departement de Physique, LIRST, Faculte Polydisciplinaire, Beni Mellal (Morocco); Cadi Ayyad University, High Energy Physics and Astrophysics Laboratory, FSSM, Marrakesh (Morocco); Chabab, M.; Masmar, K. [Cadi Ayyad University, High Energy Physics and Astrophysics Laboratory, FSSM, Marrakesh (Morocco); El Moumni, H. [Cadi Ayyad University, High Energy Physics and Astrophysics Laboratory, FSSM, Marrakesh (Morocco); Universite Ibn Zohr, Departement de Physique, Faculte des Sciences, Agadir (Morocco); Sedra, M.B. [Universite Ibn Tofail, Departement de Physique, LASIMO, Faculte des Sciences, Kenitra (Morocco)

    2016-02-15

    Motivated by recent work on asymptotically AdS{sub 4} black holes in M-theory, we investigate the thermodynamics and thermodynamical geometry of AdS black holes from M2- and M5-branes. Concretely, we consider AdS black holes in AdS{sub p+2} x S{sup 11-p-2}, where p = 2,5 by interpreting the number of M2- (and M5-branes) as a thermodynamical variable. More precisely, we study the corresponding phase transition to examine their stabilities by calculating and discussing various thermodynamical quantities including the chemical potential. Then we compute the thermodynamical curvatures from the Quevedo metric for M2- and M5-branes geometries to reconsider the stability of such black holes. The Quevedo metric singularities recover similar stability results provided by the phase-transition program. It has been shown that similar behaviors are also present in the limit of large N. (orig.)

  9. Thermal stability analysis of nonlinearly charged asymptotic AdS black hole solutions

    Science.gov (United States)

    Dehghani, M.; Hamidi, S. F.

    2017-08-01

    In this paper, the four-dimensional nonlinearly charged black hole solutions have been considered in the presence of the power Maxwell invariant electrodynamics. Two new classes of anti-de Sitter (AdS) black hole solutions have been introduced according to different amounts of the parameters in the nonlinear theory of electrodynamics. The conserved and thermodynamical quantities of either of the black hole classes have been calculated from geometrical and thermodynamical approaches, separately. It has been shown that the first law of black hole thermodynamics is satisfied for either of the AdS black hole solutions we just obtained. Through the canonical and grand canonical ensemble methods, the black hole thermal stability or phase transitions have been analyzed by considering the heat capacities with the fixed black hole charge and fixed electric potential, respectively. It has been found that the new AdS black holes are stable if some simple conditions are satisfied.

  10. QCD Condensates and Holographic Wilson Loops for Asymptotically AdS Spaces

    Energy Technology Data Exchange (ETDEWEB)

    Quevedo, R. Carcasses [Instituto Balseiro, Centro Atomico Bariloche, 8400 San Carlos de Bariloche (Argentina); CONICET, Rivadavia 1917, 1033 Buenos Aires (Argentina); Goity, Jose L. [Hampton University, Hampton, VA 23668 (United States); Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Trinchero, Roberto C. [Instituto Balseiro, Centro Atomico Bariloche, 8400 San Carlos de Bariloche (Argentina); CONICET, Rivadavia 1917, 1033 Buenos Aires (Argentina)

    2014-02-01

    The minimization of the Nambu-Goto (NG) action for a surface whose contour defines a circular Wilson loop of radius a placed at a finite value of the coordinate orthogonal to the border is considered. This is done for asymptotically AdS spaces. The condensates of dimension n = 2, 4, 6, 8, and 10 are calculated in terms of the coefficients in the expansion in powers of the radius a of the on-shell subtracted NG action for small a->0. The subtraction employed is such that it presents no conflict with conformal invariance in the AdS case and need not introduce an additional infrared scale for the case of confining geometries. It is shown that the UV value of the gluon condensates is universal in the sense that it only depends on the first coefficients of the difference with the AdS case.

  11. Wireless Ad Hoc Networks%无线特定网络--Ad Hoc网络

    Institute of Scientific and Technical Information of China (English)

    张筱; 张光昭

    2001-01-01

    Ad Hoc网络是一种没有固定结构的无线移动网络.介绍了移动Ad Hoc网络(MANETs)的主要特点和与传统有线分组交换网相比的特性,讨论了应用于Ad Hoc网络的路由机制和所需面临的问题.

  12. Secure Clustering in Vehicular Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Zainab Nayyar

    2015-09-01

    Full Text Available A vehicular Ad-hoc network is composed of moving cars as nodes without any infrastructure. Nodes self-organize to form a network over radio links. Security issues are commonly observed in vehicular ad hoc networks; like authentication and authorization issues. Secure Clustering plays a significant role in VANETs. In recent years, various secure clustering techniques with distinguishing feature have been newly proposed. In order to provide a comprehensive understanding of these techniques are designed for VANETs and pave the way for the further research, a survey of the secure clustering techniques is discussed in detail in this paper. Qualitatively, as a result of highlighting various techniques of secure clustering certain conclusions are drawn which will enhance the availability and security of vehicular ad hoc networks. Nodes present in the clusters will work more efficiently and the message passing within the nodes will also get more authenticated from the cluster heads.

  13. Introduction to AdS/CFT correspondence

    CERN Document Server

    Nastase, Horatiu

    2015-01-01

    Providing a pedagogical introduction to the rapidly developing field of AdS/CFT correspondence, this is one of the first texts to provide an accessible introduction to all the necessary concepts needed to engage with the methods, tools and applications of AdS/CFT. Without assuming anything beyond an introductory course in quantum field theory, it begins by guiding the reader through the basic concepts of field theory and gauge theory, general relativity, supersymmetry, supergravity, string theory and conformal field theory, before moving on to give a clear and rigorous account of AdS/CFT correspondence. The final section discusses the more specialised applications, including QCD, quark-gluon plasma and condensed matter. This book is self-contained and learner-focused, featuring numerous exercises and examples. It is essential reading for both students and researchers across the fields of particle, nuclear and condensed matter physics.

  14. Online Stochastic Ad Allocation: Efficiency and Fairness

    CERN Document Server

    Feldman, Jon; Korula, Nitish; Mirrokni, Vahab S; Stein, Cliff

    2010-01-01

    We study the efficiency and fairness of online stochastic display ad allocation algorithms from a theoretical and practical standpoint. In particular, we study the problem of maximizing efficiency in the presence of stochastic information. In this setting, each advertiser has a maximum demand for impressions of display ads that will arrive online. In our model, inspired by the concept of free disposal in economics, we assume that impressions that are given to an advertiser above her demand are given to her for free. Our main theoretical result is to present a training-based algorithm that achieves a (1-\\epsilon)-approximation guarantee in the random order stochastic model. In the corresponding online matching problem, we learn a dual variable for each advertiser, based on data obtained from a sample of impressions. We also discuss different fairness measures in online ad allocation, based on comparison to an ideal offline fair solution, and develop algorithms to compute "fair" allocations. We then discuss sev...

  15. Data Confidentiality in Mobile Ad hoc Networks

    CERN Document Server

    Aldabbas, Hamza; Janicke, Helge; Al-Bayatti, Ali; 10.5121/ijwmn.2012.4117

    2012-01-01

    Mobile ad hoc networks (MANETs) are self-configuring infrastructure-less networks comprised of mobile nodes that communicate over wireless links without any central control on a peer-to-peer basis. These individual nodes act as routers to forward both their own data and also their neighbours' data by sending and receiving packets to and from other nodes in the network. The relatively easy configuration and the quick deployment make ad hoc networks suitable the emergency situations (such as human or natural disasters) and for military units in enemy territory. Securing data dissemination between these nodes in such networks, however, is a very challenging task. Exposing such information to anyone else other than the intended nodes could cause a privacy and confidentiality breach, particularly in military scenarios. In this paper we present a novel framework to enhance the privacy and data confidentiality in mobile ad hoc networks by attaching the originator policies to the messages as they are sent between nod...

  16. Rotating Rindler-AdS space

    Science.gov (United States)

    Parikh, Maulik; Samantray, Prasant; Verlinde, Erik

    2012-07-01

    If the Hamiltonian of a quantum field theory is taken to be a timelike isometry, the vacuum state remains empty for all time. We search for such stationary vacua in anti-de Sitter space. By considering conjugacy classes of the Lorentz group, we find interesting one-parameter families of stationary vacua in three-dimensional anti-de Sitter space. In particular, there exists a family of rotating Rindler vacua, labeled by the rotation parameter β, which are related to the usual Rindler vacuum by nontrivial Bogolubov transformations. Rotating Rindler-AdS space possesses not only an observer-dependent event horizon but even an observer-dependent ergosphere. We also find rotating vacua in global AdS provided a certain region of spacetime is excluded.

  17. Rotating Rindler-AdS Space

    CERN Document Server

    Parikh, Maulik; Verlinde, Erik

    2011-01-01

    If the Hamiltonian of a quantum field theory is taken to be a timelike isometry, the vacuum state remains empty for all time. We search for such stationary vacua in anti-de Sitter space. By considering conjugacy classes of the Lorentz group, we find interesting one-parameter families of stationary vacua in three-dimensional anti-de Sitter space. In particular, there exists a family of rotating Rindler vacua, labeled by the rotation parameter beta, which are related to the usual Rindler vacuum by non-trivial Bogolubov transformations. Rotating Rindler-AdS space possesses not only an observer-dependent event horizon but even an observer-dependent ergosphere. We also find rotating vacua in global AdS provided a certain region of spacetime is excluded.

  18. AD Ejection Line Studies and Optics Improvements

    CERN Document Server

    Belochitskii, P

    2013-01-01

    This paper is a summary of the work we made to understand and improve the AD ejection line optics. In 2011 significant differences were noticed between the optical properties of the AD ejection line and the MAD model. Investigations started to find out the sources of discrepancy. Better understanding of the ejection line optics was obtained and corrections were applied to the model of ejection line. The beam delivery to the experiments is better understood now. The results obtained might be useful as well for the optics design of AD to ELENA transfer line. Potential problems with the fringing field model in MAD were pointed out, when bending magnets with large bending angles and small bending radius are involved.

  19. New Features in the ADS Abstract Service

    Science.gov (United States)

    Eichhorn, G.; Accomazzi, A.; Grant, C. S.; Kurtz, M. J.; ReyBacaicoa, V.; Murray, S. S.

    2001-11-01

    The ADS Abstract Service contains over 2.3 million references in four databases: Astronomy/Astrophysics/Planetary Sciences, Instrumentation, Physics/Geophysics, and Preprints. We provide abstracts and articles free to the astronomical community for all major and many smaller astronomy journals, PhD theses, conference proceedings, and technical reports. These four databases can be queried either separately of jointly. The ADS also has scanned 1.3 million pages in 180,000 articles in the ADS Article Service. This literature archive contains all major Astronomy journals and many smaller journals, as well as conference proceedings, including the abstract books from all the LPSCs back to volume 2. A new feature gives our users the ability to see list of articles that were also read by the readers of a given article. This is a powerful tool to find out what current articles are relevant in a particular field of study. We have recently expanded the citation and reference query capabilities. It allows our users to select papers for which they want to see references or citations and then retrieve these citations/references. Another new capability is the ability to sort a list of articles by their citation count. As usual, users should be reminded that the citations in ADS are incomplete because we do not obtain reference lists from all publishers. In addition, we cannot match all references (e.g. in press, private communications, author errors, some conference papers, etc.). Anyone using the citations for analysis of publishing records should keep this in mind. More work on expanding the citation and reference features is planned over the next year. ADS Home Page http://ads.harvard.edu/

  20. Flowing along the edge: spinning up black holes in AdS spacetimes with test particles

    CERN Document Server

    Rocha, Jorge V

    2014-01-01

    We investigate the consequences of throwing point particles into odd-dimensional Myers-Perry black holes in asymptotically anti-de Sitter (AdS) backgrounds. We restrict our attention to the case in which the angular momenta of the background geometry are all equal. This process allows us to test the generalization of the weak cosmic censorship conjecture to asymptotically AdS spacetimes in higher dimensions. We find no evidence for overspinning in D = 5, 7, 9 and 11 dimensions. Instead, test particles carrying the maximum possible angular momentum that still fall into an extremal rotating black hole generate a flow along the curve of extremal solutions.

  1. The generalization of charged AdS black hole specific volume and number density

    Science.gov (United States)

    Wang, Zi-Liang; He, Miao; Fang, Chao; Sun, Dao-Quan; Deng, Jian-Bo

    2017-04-01

    In this paper, by proposing a generalized specific volume, we restudy the P- V criticality of charged AdS black holes in the extended phase space. The results show that most of the previous conclusions can be generalized without change, but the ratio {\\tilde{ρ }}_c should be 3 {\\tilde{α }}/16 in general case. Further research on the thermodynamical phase transition of black hole leads us to a natural interpretation of our assumption, and more black hole properties can be generalized. Finally, we study the number density for charged AdS black hole in higher dimensions, the results show the necessity of our assumption.

  2. Double-trace deformations and entanglement entropy in AdS

    Science.gov (United States)

    Miyagawa, Taiki; Shiba, Noburo; Takayanagi, Tadashi

    2016-01-01

    We compute the bulk entanglement entropy of a massive scalar field in a Poincare AdS with the Dirichlet and Neumann boundary condition when we trace out a half space. Moreover, by taking into account the quantum back reaction to the minimal surface area, we calculate how much the entanglement entropy changes under a double-trace deformation of a holographic CFT. In the AdS3/CFT2 setup, our result agrees with the known result in 2d CFTs. In higher dimensions, our results offer holographic predictions.

  3. Double-trace deformations and entanglement entropy in AdS

    Energy Technology Data Exchange (ETDEWEB)

    Miyagawa, Taiki [Department of Physics, Kyoto University (Japan); Shiba, Noburo [Yukawa Institute for Theoretical Physics (YITP), Kyoto University (Japan); Takayanagi, Tadashi [Yukawa Institute for Theoretical Physics (YITP), Kyoto University (Japan); Kavli Institute for the Physics and Mathematics of the Universe (Kavli IPMU), University of Tokyo, Kashiwa, Chiba (Japan)

    2016-01-15

    We compute the bulk entanglement entropy of a massive scalar field in a Poincare AdS with the Dirichlet and Neumann boundary condition when we trace out a half space. Moreover, by taking into account the quantum back reaction to the minimal surface area, we calculate how much the entanglement entropy changes under a double-trace deformation of a holographic CFT. In the AdS3/CFT2 setup, our result agrees with the known result in 2d CFTs. In higher dimensions, our results offer holographic predictions. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. Double-Trace Deformations and Entanglement Entropy in AdS

    CERN Document Server

    Miyagawa, Taiki; Takayanagi, Tadashi

    2016-01-01

    We compute the bulk entanglement entropy of a massive scalar field in a Poincare AdS with the Dirichlet and Neumann boundary condition when we trace out a half space. Moreover, by taking into account the quantum back reaction to the minimal surface area, we calculate how much the entanglement entropy changes under a double-trace deformation of a holographic CFT. In the AdS3/CFT2 setup, our result agrees with the known result in 2d CFTs. In higher dimensions, our results offer holographic predictions.

  5. Superradiance Instability of Small Rotating AdS Black Holes in Arbitrary Dimensions

    CERN Document Server

    Delice, Özgür

    2015-01-01

    We investigate the stability of $D$ dimensional singly rotating Myers-Perry-AdS black holes under superradiance against scalar field perturbations. It is well known that small four dimensional rotating or charged AdS black holes are unstable against superradiance instability of a scalar field. Recent works extended the existence of this instability to five dimensional rotating charged AdS black holes or static charged AdS Black holes in arbitrary dimensions. In this work we analytically prove that, rotating small AdS black holes in arbitrary dimensions also show superradiance instability irrespective of the value of the (positive) angular momentum quantum number. To do this we solve the Klein-Gordon equation in the slow rotation, low frequency limit. By using the asymptotic matching technique, we are able to calculate the real and imaginary parts of the correction terms to the frequency of the scalar field due to the presence of the black hole, confirming the presence of superradiance instability. We see that...

  6. Horizon Conformal Field Theories from $AdS_2$ Black Holes

    CERN Document Server

    Halyo, Edi

    2015-01-01

    We show that the very near horizon region of nonextreme black holes, which can be described by horizon CFTs, are related to $AdS_2$ Rindler spaces. The latter are $AdS_2$ black holes with specific masses and can be described by states of either $D=1$ or $D=2$ CFTs. The central charges of these CFTs and the conformal weights of their states that correspond to the nonextreme black holes exactly match those predicted by the horizon CFTs, providing supporting evidence for this description.

  7. Vehicular ad hoc network security and privacy

    CERN Document Server

    Lin, X

    2015-01-01

    Unlike any other book in this area, this book provides innovative solutions to security issues, making this book a must read for anyone working with or studying security measures. Vehicular Ad Hoc Network Security and Privacy mainly focuses on security and privacy issues related to vehicular communication systems. It begins with a comprehensive introduction to vehicular ad hoc network and its unique security threats and privacy concerns and then illustrates how to address those challenges in highly dynamic and large size wireless network environments from multiple perspectives. This book is richly illustrated with detailed designs and results for approaching security and privacy threats.

  8. iAd Production Beginner's Guide

    CERN Document Server

    Collier, Ben

    2012-01-01

    This beginner's guide focuses on getting you through all the major learning points in a smooth, logical order. You'll also see how to avoid some common pitfalls. This book is for brands, advertisers and developers who want to create compelling, emotive, iAd advertisements that generate revenue and increase brand awareness. You don't need previous experience of creating adverts or apps for iPhone and iPad, as you'll be taken through the entire process to make motion-rich, beautiful ads.

  9. Intermittently connected mobile ad hoc networks

    CERN Document Server

    Jamalipour, Abbas

    2011-01-01

    In the last few years, there has been extensive research activity in the emerging area of Intermittently Connected Mobile Ad Hoc Networks (ICMANs). By considering the nature of intermittent connectivity in most real word mobile environments without any restrictions placed on users' behavior, ICMANs are eventually formed without any assumption with regard to the existence of a end-to-end path between two nodes wishing to communicate. It is different from the conventional Mobile Ad Hoc Networks (MANETs), which have been implicitly viewed as a connected graph with established complete paths betwe

  10. QCD condensates in ADS/QCD

    DEFF Research Database (Denmark)

    Bechi, Jacopo

    2009-01-01

    This paper focuses on some issues about condensates and renormalization in AdS/QCD models. In particular we consider the consistency of the AdS/QCD approach for scale dependent quantities as the chiral condensate questioned in some recent papers and the 4D meaning of the 5D cosmological constant...... in a model in which the QCD is dual to a 5D gravity theory. We will be able to give some arguments that the cosmological constant is related to the QCD gluon condensate....

  11. Adding value to corporate ventures through governance

    DEFF Research Database (Denmark)

    Skat-Rørdam, Peter

    2005-01-01

    than the control mechanisms widely explored in connection with the governance of large public corporations. The paper provides examples of how value can be added as well as perspectives on the challenges and effectivenes here-off as evaluated by venture CEO's and venture board members......This working paper examines the governance of corporate ventures based upon a qualitative interview based case study of a European industrial conglomerate. The purpose is to explore the value adding mechanisms of governance, that are considered more critical to the success of corporate ventures...

  12. The Stylistic Analysis of car ads languages

    Institute of Scientific and Technical Information of China (English)

    张伟苹

    2014-01-01

    Automotive advertising language is mix of phonetics, vocabulary, rhetoric, syntax, and discourse language etc., and owning a strong promotional effect which can functioned as a bridge between language expression and promotion system for es-sential products and consumers. As a kind of the commercial advertising, car advertising with its own unique language features not only for product considerably, but also enriches the advertising language. In order to analysis the car ads, this article draws at-tention from the aspects of the phonetics, vocabulary, rhetoric and syntax features, and aims to get a further and better analysis or understanding of the car ads Languages.

  13. Adding value to corporate ventures through governance

    DEFF Research Database (Denmark)

    Skat-Rørdam, Peter

    2005-01-01

    This working paper examines the governance of corporate ventures based upon a qualitative interview based case study of a European industrial conglomerate. The purpose is to explore the value adding mechanisms of governance, that are considered more critical to the success of corporate ventures...... than the control mechanisms widely explored in connection with the governance of large public corporations. The paper provides examples of how value can be added as well as perspectives on the challenges and effectivenes here-off as evaluated by venture CEO's and venture board members...

  14. Ad hoc networks telecommunications and game theory

    CERN Document Server

    Benslama, Malek; Batatia, Hadj

    2015-01-01

    Random SALOHA and CSMA protocols that are used to access MAC in ad hoc networks are very small compared to the multiple and spontaneous use of the transmission channel. So they have low immunity to the problems of packet collisions. Indeed, the transmission time is the critical factor in the operation of such networks. The simulations demonstrate the positive impact of erasure codes on the throughput of the transmission in ad hoc networks. However, the network still suffers from the intermittency and volatility of its efficiency throughout its operation, and it switches quickly to the satura

  15. Adding Users to the Website Design Process

    Science.gov (United States)

    Tomeo, Megan L.

    2012-01-01

    Alden Library began redesigning its website over a year ago. Throughout the redesign process the students, faculty, and staff that make up the user base were added to the conversation by utilizing several usability test methods. This article focuses on the usability testing conducted at Alden Library and delves into future usability testing, which…

  16. Report on Experiment AD-4/ACE

    CERN Document Server

    Holzscheiter, M H

    2014-01-01

    After 7 years running the AD-4 Experiment at antiproton momentum of 502 MeV/c we have now assembled a complete data set and are preparing to combine all years into a single analysis of RBE vs. Depth for an antiproton beam stopping in water. We describe experimental challenges and computational issues which need to be resolved to achieve this final step.

  17. Adding calcium improves lithium ferrite core

    Science.gov (United States)

    Lessoff, H.

    1969-01-01

    Adding calcium increases uniformity of grain growth over a wide range of sintering temperatures and reduces porosity within the grain. Ferrite cores containing calcium have square hysteresis loops and high curie temperatures, making them useful in coincident current memories of digital electronic computers.

  18. Estimating the Value Added Product Life Cycle

    OpenAIRE

    Gedikoglu, Haluk; Parcell, Joseph L.; Patterson, David J.; Randle, Richard

    2006-01-01

    This research analyzes factors affecting product and profit life-cycles for new value added products. The methodology used shows how sales and profits evolve and how exogenous factors affecting sales and profits. Results indicate that producers can increase the level of sales and profits over time through initial marketing efforts.

  19. Value-Added Modeling in Physical Education

    Science.gov (United States)

    Hushman, Glenn; Hushman, Carolyn

    2015-01-01

    The educational reform movement in the United States has resulted in a variety of states moving toward a system of value-added modeling (VAM) to measure a teacher's contribution to student achievement. Recently, many states have begun using VAM scores as part of a larger system to evaluate teacher performance. In the past decade, only "core…

  20. Manifold invariants affect dynamics in ADS gravity

    CERN Document Server

    Liko, Tomas

    2013-01-01

    The first-order Holst action with negative cosmological constant is rendered finite by requiring functional differentiability on the configuration space of tetrads and connections. The surface terms that arise in the action for ADS gravity are equivalent to the Euler and Pontryagin densities with fixed weight factors; these terms modify the Noether charges that arise from diffeomorphism invariance of the action.

  1. CERN Enters the Second Year AD

    CERN Document Server

    2001-01-01

    2001 is the year that physics at CERN's new Antiproton Decelerator (AD) really gets up to speed. Changes to the AD since 2000 mean that this year the three experiments, ASACUSA, ATHENA, and ATRAP have had more intense antiproton beams to work with since physics started on 7 May. CERN's Antiproton Decelerator - major improvements for 2001. The AD is a unique machine. Its job is to decelerate not accelerate particle beams, and it has to handle beam energies that vary by an unprecedented factor of 35 from injection to ejection. Since the machine was designed to operate at fixed energy in its first incarnation as a collector of antiprotons for CERN's 1980s proton antiproton collider, this factor of 35 presented a big challenge to the AD team. The team's design goal was to hang onto a quarter of the injected antiprotons through their vertiginous fall in energy, and to repeat the deceleration cycle once per minute. Improvements to the machine over the winter shutdown and through the first four weeks of 2001 run...

  2. Added value: The differences that count

    Directory of Open Access Journals (Sweden)

    Dominique Bouchet

    2012-08-01

    Full Text Available Clinging to a simplistic conceptualization of the concept of added value might impair our capability to develop insights to what really matters today when companies seek to make differences within the global market. Today it is more necessary than ever to take into account the importance of language and culture as competitive factors.

  3. Test Scaling and Value-Added Measurement

    Science.gov (United States)

    Ballou, Dale

    2009-01-01

    Conventional value-added assessment requires that achievement be reported on an interval scale. While many metrics do not have this property, application of item response theory (IRT) is said to produce interval scales. However, it is difficult to confirm that the requisite conditions are met. Even when they are, the properties of the data that…

  4. The Added Value of Business Models

    NARCIS (Netherlands)

    Vliet, Harry van

    2014-01-01

    An overview of innovations in a particular area, for example retail developments in the fashion sector (Van Vliet, 2014), and a subsequent discussion about the probability as to whether these innovations will realise a ‘breakthrough’, has to be supplemented with the question of what the added value

  5. Secret Symmetries in AdS/CFT

    CERN Document Server

    de Leeuw, Marius; Moriyama, Sanefumi; Regelskis, Vidas; Torrielli, Alessandro

    2012-01-01

    We discuss special quantum group (secret) symmetries of the integrable system associated to the AdS/CFT correspondence. These symmetries have by now been observed in a variety of forms, including the spectral problem, the boundary scattering problem, n-point amplitudes, the pure-spinor formulation and quantum affine deformations.

  6. Added Value of Employee Financial Participation

    NARCIS (Netherlands)

    Poutsma, E.; Kaarsemaker, E.C.A.

    2015-01-01

    This chapter broadens our understanding of the added value of employee financial participation. Financial participation is a generic term for the participation of employees in profit and enterprise results including equity of their employing firm. In general, there are two forms of employee

  7. ENEA presenta sistema ADS per trattamento scorie

    CERN Multimedia

    2002-01-01

    "Arriva il sistema Ads (Accelerator driven system) per il trattamento dei rifiuti radioattivi. Lo studio di fattibilita' per l' innovativa tecnologia, realizzato da un gruppo di lavoro congiunto Enea, Cea, Cern e Ansaldo, e' stato presentato oggi nel corso di un workshop presieduto dal premio Nobel per la fisica, Carlo Rubbia" (1/2 page).

  8. Value Added School Review Field Guide

    Science.gov (United States)

    Alberta Education, 2009

    2009-01-01

    The "Value-Added School Review (VSR)" is an analytical model designed to assist schools in identifying and addressing opportunities for school improvement. The model works best when it is focused purposefully on students and the student learning outcomes as defined in the "Guide to Education". It complements the processes…

  9. Added Value of Employee Financial Participation

    NARCIS (Netherlands)

    Poutsma, F.; Kaarsemaker, E.C.A.

    2015-01-01

    This chapter broadens our understanding of the added value of employee financial participation. Financial participation is a generic term for the participation of employees in profit and enterprise results including equity of their employing firm. In general, there are two forms of employee financia

  10. Context discovery in ad-hoc networks

    NARCIS (Netherlands)

    Liu, Fei

    2011-01-01

    Mobile ad-hoc networks (MANETs) are more and more present in our daily life. Such networks are often composed of mobile and battery-supplied devices, like laptops and PDAs. With no requirement for infrastructure support, MANETs can be used as temporary networks, such as for conference and office env

  11. Double Thermalization via AdS/CFT

    CERN Document Server

    Ali-Akbari, M; Kishani-Farahani, A; Shafie, N

    2016-01-01

    We exploit the AdS/CFT correspondence to investigate thermalization in an N=2 strongly coupled gauge theory including massless fundamental matter (quark). More precisely, we consider the response of a zero temperature state of the gauge theory under variation of an external electric field leading to a time-dependent current. The holographic dual of the above set-up is given by introducing a time-dependent electric field on the probe D7-brane embedded in an AdS_5 X S^5 background. In the dual gravity theory, due to a time-dependent electric field an apparent horizon forms on the brane which, according to AdS/CFT dictionary, is the counterpart of the thermalization process in the gauge theory. We classify different functions for time-dependent electric field and study their effect on the apparent horizon formation. In the case of pulse functions where the electric field varies from zero to zero, apart from non-equilibrium phase, we observe that two apparent horizons form on the brane. On the gauge theory side, ...

  12. Integrable strings for AdS/CFT

    NARCIS (Netherlands)

    Borsato, R.

    2015-01-01

    In this thesis we discuss certain models that arise in string theory, motivated by the AdS/CFT correspondence. For these models there exists a notion of “quantum Integrability”. Although this term is very broad, for us it will be used in the sense of factorisation of scattering for models in 1+1 dim

  13. Correction terms to Newton law due to induced gravity in AdS background

    CERN Document Server

    Ito, M

    2003-01-01

    We calculate small correction terms to gravitational potential on Randall-Sundrum brane with an induced Einstein term. The behaviors of the correction terms depend on the magnitudes of $AdS$ radius $k^{-1}$ and a characteristic length scale $\\l$ of model. We present the gravitational potential for arbitrary $k$ and $\\l$ at all distances.

  14. D-branes from Pure Spinor Superstring in AdS_5 x S^5 Background

    CERN Document Server

    Hanazawa, Sota

    2016-01-01

    We examine the surface term for the BRST transformation of the open pure spinor superstring in an AdS_5 x S^5 background. We find that the boundary condition to eliminate the surface term leads to a classification of possible configurations of 1/2 supersymmetric D-branes.

  15. Geometry and supersymmetry of heterotic warped flux AdS backgrounds

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2015-07-01

    We classify the geometries of the most general warped, flux AdS backgrounds of heterotic supergravity up to two loop order in sigma model perturbation theory. We show under some mild assumptions that there are no AdS n backgrounds with n ≠ 3. Moreover the warp factor of AdS3 backgrounds is constant, the geometry is a product AdS 3 × M 7 and such solutions preserve, 2, 4, 6 and 8 supersymmetries. The geometry of M 7 has been specified in all cases. For 2 supersymmetries, it has been found that M 7 admits a suitably restricted G 2 structure. For 4 supersymmetries, M 7 has an SU(3) structure and can be described locally as a circle fibration over a 6-dimensional KT manifold. For 6 and 8 supersymmetries, M 7 has an SU(2) structure and can be described locally as a S 3 fibration over a 4-dimensional manifold which either has an anti-self dual Weyl tensor or a hyper-Kähler structure, respectively. We also demonstrate a new Lichnerowicz type theorem in the presence of α' corrections.

  16. Finite temperature effective action, AdS_5 black holes, and 1/N expansion

    CERN Document Server

    Alvarez-Gaumé, Luís; Liu, H; Wadia, S; Alvarez-Gaume, Luis; Gomez, Cesar; Liu, Hong; Wadia, Spenta

    2005-01-01

    We propose a phenomenological matrix model to study string theory in AdS_5 \\times S_5 in the canonical ensemble. The model reproduces all the known qualitative features of the theory. In particular, it gives a simple effective potential description of Euclidean black hole nucleation and the tunnelling between thermal AdS and the big black hole. It also has some interesting predictions. We find that there exists a critical temperature at which the Euclidean small black hole undergoes a Gross-Witten phase transition. We identify the phase transition with the Horowitz-Polchinski point where the black hole horizon size becomes comparable to the string scale. The appearance of the Hagedorn divergence of thermal AdS is due to the merger of saddle points corresponding to the Euclidean small black hole and thermal AdS. The merger can be described in terms of a cusp (A_3) catastrophe and divergences at the perturbative string level are smoothed out at finite string coupling using standard techniques of catastrophe the...

  17. Parametrization of cosets for AdS5xS5 superstring action

    CERN Document Server

    Siegel, W

    2015-01-01

    A formulation recently proposed [arXiv:1506.07706] as an alternative to the usual coset PSU(2,2|4)/USp(2,2)USp(4) for the superspace geometry of the Type IIB superstring on an AdS5xS5 background is shown to be a particular parametrization of this coset. Standard methods can then be applied.

  18. On Critical Massive (Super)Gravity in adS(3)

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Hohm, Olaf; Rosseel, Jan; Sezgin, Ergin; Townsend, Paul K.; Aldaya,; Barcelo, C; Jaramillo, JL

    2011-01-01

    We review the status of three-dimensional "general massive gravity" (GMG) in its linearization about an anti-de Sitter (adS) vacuum, focusing on critical points in parameter space that yield generalizations of "chiral gravity". We then show how these results extend to,N = 1 super-GMG, expanded about

  19. Classical strings in $AdS_4\\times\\mathbb{CP}^3$ with three angular momenta

    CERN Document Server

    Giardino, Sergio

    2011-01-01

    In this paper, rotating strings in three directions of $AdS_4 \\times \\mathbb{CP}^3$ geometry are studied; its divergent energy limit, and conserved charges are also determined. An interpretation of these configurations as either giant magnons or spiky strings are discussed.

  20. Near horizon data and physical charges of extremal AdS black holes

    NARCIS (Netherlands)

    Astefanesei, D.; Banerjee, N.; Dutta, S.

    2011-01-01

    We compute the physical charges and discuss the properties of a large class of five-dimensional extremal AdS black holes by using the near horizon data. Our examples include baryonic and electromagnetic black branes, as well as supersymmetric spinning black holes. In the presence of the gauge Chern–

  1. S-matrix for strings on η-deformed AdS5 x S5

    NARCIS (Netherlands)

    Arutyunov, G.E.; Borsato, R.; Frolov, S.

    2013-01-01

    We determine the bosonic part of the superstring sigma model Lagrangian on η-deformed AdS5 x S5, and use it to compute the perturbative world-sheet scattering matrix of bosonic particles of the model. We then compare it with the large string tension limit of the q-deformed S-matrix and find exact ag

  2. Jordanian deformations of the AdS5×S5 superstring

    NARCIS (Netherlands)

    Kawaguchi, I.; Matsumoto, T.; Yoshida, K

    2014-01-01

    We consider Jordanian deformations of the AdS_5xS^5 superstring action. The deformations correspond to non-standard q-deformation. In particular, it is possible to perform partial deformations, for example, only for the S^5 part. Then the classical action and the Lax pair are constructed with a line

  3. S-matrix for strings on η-deformed AdS5 x S5

    NARCIS (Netherlands)

    Arutyunov, Gleb; Borsato, Riccardo; Frolov, Sergey

    2013-01-01

    We determine the bosonic part of the superstring sigma model Lagrangian on η-deformed AdS5 × S5, and use it to compute the perturbative world-sheet scattering matrix of bosonic particles of the model. We then compare it with the large string tension limit of the q-deformed S-matrix and find exact ag

  4. The spectral problem for strings on twisted AdS5 ×S5

    NARCIS (Netherlands)

    de Leeuw, M.; van Tongeren, S.J.

    2012-01-01

    We discuss the spectral problem for integrable superstrings on generically twisted AdS5 × S5, meaning all its orbifolds and TsT transformed versions. We explicitly give the asymptotic description of these theories through a twisted transfer matrix, and carefully match the geometric deformations with

  5. Simplified TBA equations of the AdS5 × S5 mirror model

    NARCIS (Netherlands)

    Arutyunov, G.E.; Frolov, S.

    2009-01-01

    We use the recently found integral representation for the dressing phase in the kinematic region of the mirror theory to simplify the TBA equations for the AdS5 × S5 mirror model. The resulting set of equations provides an efficient starting point for both analytic and numerical studies.

  6. S-matrix for strings on $\\eta$-deformed AdS5 x S5

    CERN Document Server

    Arutyunov, Gleb; Frolov, Sergey

    2014-01-01

    We determine the bosonic part of the superstring sigma model Lagrangian on $\\eta$-deformed AdS5 x S5, and use it to compute the perturbative world-sheet scattering matrix of bosonic particles of the model. We then compare it with the large string tension limit of the q-deformed S-matrix and find exact agreement.

  7. Bound state transfer matrix for AdS5 × S5 superstring

    NARCIS (Netherlands)

    Arutyunov, G.E.; de Leeuw, M.; Suzuki, R.; Torrielli, A.

    2009-01-01

    We apply the algebraic Bethe ansatz technique to compute the eigenvalues of the transfer matrix constructed from the general bound state S-matrix of the light-cone AdS5 × S5 superstring. This allows us to verify certain conjectures on the quantum characteristic function, and to extend them to the ge

  8. The S-matrix of the AdS5xS5 superstring

    NARCIS (Netherlands)

    de Leeuw, M.

    2010-01-01

    According to the gauge-string duality conjecture, the spectrum of scaling dimensions of composite gauge invariant operators of the planar maximally supersymmetric Yang-Mills theory in four dimensions should be equivalent to the energy spectrum of superstrings propagating in the AdS5 x S5 space-time,

  9. D-branes from pure spinor superstring in AdS5 × S5 background

    Science.gov (United States)

    Hanazawa, Sota; Sakaguchi, Makoto

    2017-01-01

    We examine the surface term for the BRST transformation of the open pure spinor superstring in an AdS5 ×S5 background. We find that the boundary condition to eliminate the surface term leads to a classification of possible configurations of 1/2 supersymmetric D-branes.

  10. The bound state S-matrix for AdS5×S5 superstring

    NARCIS (Netherlands)

    Arutyunov, G.E.; de Leeuw, M.; Torrielli, A.

    2009-01-01

    We determine the S-matrix that describes scattering of arbitrary bound states in the light-cone string theory in AdS5×S5. The corresponding construction relies on the Yangian symmetry and the superspace formalism for the bound state representations. The basic analytic structure supporting the S-matr

  11. Searching for AdS_3 waves and Asymptotically Lifshitz black holes in R^3-NMG

    CERN Document Server

    Anastasiou, Giorgos G; Vagenas, Elias C

    2013-01-01

    In this paper we consider the structure of the $AdS_3$ vacua in $R^3$ expansion of the New Massive Gravity ($R^3$-NMG). We obtain the degeneracies of the $AdS_3$ vacua at several points of the parametric space. Additionally, following a specific analysis we show that $AdS_3$ wave solutions are present. Using these wave solutions, we single out two special points of the parametric space for which logarithmic terms appear in the solutions. The first one is a point at which the effective mass of the wave profile which is interpreted as a scalar mode, completely saturates the Breitenlohner-Freedman bound of the $AdS_3$ space in which the wave is propagating. The second special point is a point at which the central charge of the theory vanishes. Furthermore, we investigate the possibility of asymptotically Lifshitz black solutions to be present in the three-dimensional $R^3$-NMG. We derive analytically the Lifshitz vacua considering specific relations between the mass parameters of $R^3$-NMG. A certain polynomial ...

  12. Phase transitions of magnetic AdS4 black holes with scalar hair

    NARCIS (Netherlands)

    Hristov, K.; Toldo, C.; Vandoren, S.

    2013-01-01

    We determine the thermodynamic properties of a class of spherically symmetric and static black holes in AdS4 with magnetic charges and scalar hair. These black holes are solutions in four-dimensional N=2 gauged supergravity that can arise from 11-dimensional supergravity compactified on S7. At zero

  13. The differential effects of position, ad and reader characteristics on readers' processing of newspaper ads

    NARCIS (Netherlands)

    Smit, E.G.; Neijens, P.C.; Heath, R.

    2013-01-01

    Building on previous research on the processing of newspaper ads, this comprehensive field study, with 26,556 newspaper readers and 290 unique advertisements, investigated the combined effects of position in the newspaper, ad characteristics and reader characteristics. The results show a

  14. EVH Black Holes, AdS3 Throats and EVH/CFT Proposal

    CERN Document Server

    Sheikh-Jabbaria, M M

    2011-01-01

    Within class of generic black holes there are extremal black holes (with vanishing Hawking temperature T) and vanishing horizon area Ah, but with finite Ah/T ratio,the Extremal Vanishing Horizon (EVH) black holes. We study the near horizon limit of a four dimensional EVH black hole solution to a generic (gauged) Einstein-Maxwell dilaton theory and show that in the near horizon limit they develop a throat which is a pinching orbifold limit of AdS3. This is an extension of the well known result for extremal black holes the near horizon limit of which contains an AdS2 throat. We show that in the near EVH near horizon limit the pinching AdS3 factor turns to a pinching BTZ black hole and that this near horizon limit is indeed a decoupling limit. We argue that the pinching AdS3 or BTZ orbifold is resolved if the near horizon limit is accompanied by taking the 4d Newton constant G4 to zero such that the Bekenstein-Hawking entropy S = Ah/(4G4) remains finite. We propose that in this limit the near horizon EVH black h...

  15. F-string Solution in AdS4 X CP3 PP-wave Background

    CERN Document Server

    Banerjee, Gourav

    2016-01-01

    We present supergravity solution for F-string in pp wave background obtained from AdS4 X CP3 with zero flat directions.The classical solution is shown to break all space-time supersymmetries. We explicitly write down the standard as well as supernumerary Killing spinors both for the background and F-string solution.

  16. The Complexity of Identifying Ryu-Takayanagi Surfaces in AdS3/CFT2

    CERN Document Server

    Bao, Ning

    2016-01-01

    We present a constructive algorithm for the determination of Ryu-Takayanagi surfaces in AdS3/CFT2 which exploits previously noted connections between holographic entanglement entropy and max-flow/min-cut. We then characterize its complexity as a polynomial time algorithm.

  17. The complexity of identifying Ryu-Takayanagi surfaces in AdS3/CFT2

    Science.gov (United States)

    Bao, N.; Chatwin-Davies, A.

    2016-11-01

    We present a constructive algorithm for the determination of Ryu-Takayanagi surfaces in AdS3/CFT2 which exploits previously noted connections between holographic entanglement entropy and max-flow/min-cut. We then characterize its complexity as a polynomial time algorithm.

  18. Near horizon data and physical charges of extremal AdS black holes

    NARCIS (Netherlands)

    Astefanesei, D.; Banerjee, N.; Dutta, S.

    2011-01-01

    We compute the physical charges and discuss the properties of a large class of five-dimensional extremal AdS black holes by using the near horizon data. Our examples include baryonic and electromagnetic black branes, as well as supersymmetric spinning black holes. In the presence of the gauge Chern–

  19. String hypothesis for the AdS5 × S5 mirror

    NARCIS (Netherlands)

    Arutyunov, G.E.; Frolov, S.

    2009-01-01

    We discuss the states which contribute in the thermodynamic limit of the mirror theory, the latter is obtained from the light-cone gauge-fixed string theory in the AdS_5 x S^5 background by the double-Wick rotation. We analyze the Bethe-Yang equations for the mirror theory and formulate the string h

  20. The differential effects of position, ad and reader characteristics on readers' processing of newspaper ads

    NARCIS (Netherlands)

    Smit, E.G.; Neijens, P.C.; Heath, R.

    2013-01-01

    Building on previous research on the processing of newspaper ads, this comprehensive field study, with 26,556 newspaper readers and 290 unique advertisements, investigated the combined effects of position in the newspaper, ad characteristics and reader characteristics. The results show a differentia