Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

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41421 Publications

Metal island/polymer composite films: novel properties and applications

Oates, T. W. H.

There is no abstract provided.

  • Lecture (others)
    Group of Macromolecular Physics, Charles University, 10.12.2004, Prague, Czech Republic

Permalink: https://www.hzdr.de/publications/Publ-9832
Publ.-Id: 9832


Titanium-based layers prepared by metal plasma immersion ion implantation and deposition as hemocompatible surfaces

Tsyganov, I.; Maitz, M. F.; Richter, E.

There is no abstract provided.

  • Lecture (Conference)
    5th International Young Scientists Conference on Problems of Optics and High Technology Material Science, 28.-31.10.2004, Kyiv, Ukraine

Permalink: https://www.hzdr.de/publications/Publ-9831
Publ.-Id: 9831


Structure and properties of titanium based coatings prepared by metal plasma immersion ion implantation and deposition

Tsyganov, I.; Maitz, M. F.; Wieser, E.; Richter, E.; Reuther, H.

There is no abstract provided.

  • Poster
    9 Int. Conf. on Plasma Surface Engineering, 13.-17.09.2004, Garmisch-Partenkirchen, Germany

Permalink: https://www.hzdr.de/publications/Publ-9830
Publ.-Id: 9830


Blood Compatibility of Titanium-Based Coatings Prepared by Metal Plasma Immersion Ion Implantation and Deposition

Tsyganov, I. A.; Maitz, M. F.; Wieser, E.

There is no abstract provided.

  • Lecture (Conference)
    7th International Conference on Modification of Materials with Particle Beams and Plasma Flows, 25.-29.07.2004, Tomsk, Russia

Permalink: https://www.hzdr.de/publications/Publ-9829
Publ.-Id: 9829


Electrical resistance of ultrathin films determined by in situ spectroscopic ellipsometry

Oates, T. W. H.

There is no abstract provided.

  • Lecture (Conference)
    5th International Young Scientists Conference, 28.-31.10.2004, Kyiv, Ukraine

Permalink: https://www.hzdr.de/publications/Publ-9828
Publ.-Id: 9828


Optical and electronic properties of ultrathin silver films for biosensor applications

Oates, T. W. H.; Ryves, L.; Bilek, M. M. M.; Mckenzie, D. R.

There is no abstract provided.

  • Lecture (Conference)
    EMRS Fall meeting, 06.-10.09.2004, Warsaw, Poland

Permalink: https://www.hzdr.de/publications/Publ-9827
Publ.-Id: 9827


Blood compatibility of metal oxide surfaces prepared by metal plasma immersion ion implantation and deposition

Maitz, M. F.; Fitz, T.; Pham, M. T.; Richter, E.

There is no abstract provided.

  • Lecture (Conference)
    7th World Biomaterials Congress, 17.-21.05.2004, Sydney, Australia

Permalink: https://www.hzdr.de/publications/Publ-9826
Publ.-Id: 9826


Modified NiTi for improved biocompatibility

Maitz, M. F.; Pham, M. T.; Shevchenko, N.

There is no abstract provided.

  • Poster
    6th Asian Symposium on Biomedical Materials, 19.-22.07.2004, Chengdu, China

Permalink: https://www.hzdr.de/publications/Publ-9825
Publ.-Id: 9825


Combined application of multiple ion energies for simultaneous growth and stress relaxation at thin film deposition

Kolitsch, A.; Abendroth, B.; Gago, R.; Fitz, R.; Möller, W.

There is no abstract provided.

  • Invited lecture (Conferences)
    ECAART-8 2004, 8th European Conference on Accelerators in Applied Research and Technology, 20.-24.09.2004, Paris, France

Permalink: https://www.hzdr.de/publications/Publ-9824
Publ.-Id: 9824


Application of combined low and high energy ion assistance for film formation and stress relaxation of cBN thin films

Kolitsch, A.; Abendroth, B.; Gago, R.; Fitz, R.; Möller, W.

There is no abstract provided.

  • Invited lecture (Conferences)
    IV International Symposium “Ion Implantation and Other Application of Ions and Electrons” ION 2004, 14.-17.04.2004, Kazimierz Dolny, Poland

Permalink: https://www.hzdr.de/publications/Publ-9823
Publ.-Id: 9823


Bonding environment in films deposited from Ar/CH4 and Ar/CH4/N2 ECR discharge: effect of voltage polarization on the growth process

Camero, M.; Gago, R.; Gómez-Aleixandre, C.; Albella, J. M.

There is no abstract provided.

  • Poster
    PSE2004, 13.-17.09.2004, Garmisch-Partenkirchen, Germany

Permalink: https://www.hzdr.de/publications/Publ-9822
Publ.-Id: 9822


Symmetries in nuclear structure

Frauendorf, S.

The symmetries of the rotating mean field and their consequences for rotational bands are discussed. Chirality of rotating triaxial nuclei differs from the chirality of molecules and mass-less particles, because the roles of space inversion and time reversal are exchanged. The experimental consequences of chirality and mass regions where it is expected are discussed. Rotational bands of the predicted shapes with tetrahedral symmetry are ΔI=2 sequences with alternating parity. Breaking of the isospin rotational symmetry by the isovector pair field leads to isorotational bands. The low spin spectra of N=Z nuclei can be explained combining mean-field calculations that take only isovector pairing into account with the concept of isorotational bands. The possible appearance of an isoscalar pair field at high spin would manifest as a pair-rotational band consisting of even-spin states in the even-even and odd-spin states in odd-odd N=Z nuclei.

  • Nuclear Physics A 752(2005), 203-212

Permalink: https://www.hzdr.de/publications/Publ-9821
Publ.-Id: 9821


Structural and optical properties of ß-FeSi2 phase prepared by ion beam synthesis

Ayache, R.; Bouabellou, A.; Eichhorn, F.; Richter, E.

There is no abstract provided.

  • Poster
    E-MRS Fall Meeting, 06.-10.09.2004, Warsaw, Poland

Permalink: https://www.hzdr.de/publications/Publ-9820
Publ.-Id: 9820


Structural and optical properties of ß-FeSi2 phases prepared by ion beam synthesis

Ayache, R.; Bouabellou, A.; Richter, E.

  • Poster
    E-MRS Spring Meeting, 24.-28.05.2004, Strasbourg, France

Permalink: https://www.hzdr.de/publications/Publ-9819
Publ.-Id: 9819


Design and synthesis of radiotracers for imaging cyclooxygenase-2(COX-2) expression

Wüst, F.

kein Abstract verfügbar

  • Invited lecture (Conferences)
    Seminars on Drug Discovery and Development, 09.05.2007, Zürich, Schweiz

Permalink: https://www.hzdr.de/publications/Publ-9818
Publ.-Id: 9818


Optical characterization of beta-FeSi2 layers formed by ion beam synthesis

Ayache, R.; Bouabellou, A.; Richter, E.

There is no abstract provided.

  • Poster
    E-MRS Spring Meeting, 24.-28.05.2004, Strasbourg, France

Permalink: https://www.hzdr.de/publications/Publ-9817
Publ.-Id: 9817


Synthesis of 18F-labeled stilbenes from 4-(18F)fluorobenzaldehyde using the Horner-Wadsworth-Emmons reaction

Wüst, F.; Gester, S.; Pietzsch, J.

Introduction:

The coupling of phosphonic acid esters with carbonyl compounds, also referred to as the Horner-Wadsworth-Emmons reaction, represents a powerful carbonyl olefination reaction to form C-C double bonds, exhibiting E-configuration exclusively.
This work describes the application of the Horner-Wadsworth-Emmons reaction as novel labeling technique in 18F-chemistry. Various 18F-labeled E-configured stilbenes could be synthesized through the coupling of benzylic phosphonic acid esters with readily available 4-[18F]fluorobenzaldehyde 1 as labeling precursor (Fig. 1).

Experimental:

The carbonyl-olefination reaction was performed via a “multi-step/one-pot” reaction by the coupling of benzylic phosphonic acid esters (3,5-bis-methoxymethoxybenzyl)-phosphonic acid diethyl ester 2a, (4-methoxymethoxybenzyl)-phosphonic acid diethyl ester 3a and (4-dimethyl-aminobenzyl)phosphonic acid diethyl ester 4a) with 4-[18F]fluorobenzaldehyde to give the corresponding 18F-labeled stilbenes [18F]2b, [18F]3b and [18F]4b exclusively as the expected E-isomers after deprotection. The radiochemical yields ranged from 9 to 22% (based upon [18F]fluoride, including HPLC purification). The specific activity reached up to 90 GBq/μmol.

Results and Discussion:

The reaction can be applied for the synthesis of polyphenolic compounds and aromatic amines bearing an E-configured stilbene backbone as pharmaceutically interesting compounds. Several E-configured stilbene-based polyphenols are known to be potential anticancer compounds. In the case of amine group-containing stilbene compound [18F]4b, structural comparable stilbenes have been reported as potential ligands to bind to Aβ-plaques found in the brain of patients with the neurodegenerative Alzheimer's disease. Preliminary radiopharmacological studies including small animal PET of compound [18F]4b in normal rats showed promising brain uptake. Results on the radiopharmacological characterization of compound [18F]4b will be presented.

Conclusion:

The described method opens a convenient access to a large number of 18F-labeled compounds bearing an E-configured stilbene backbone.

Acknowledgement: The authors wish to thank S. Preusche for radioisotope production and T. Krauss for technical assistance.

Keywords: Stilbenes; [18F]Fluorobenzaldehyde; Horner-Wadsworth-Emmons Reaction

  • Lecture (Conference)
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S54
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9816
Publ.-Id: 9816


Ion-induced stress relaxation during magnetron sputtering deposition of cubic boron nitride thin films

Abendroth, B.; Gago, R.; Eichhorn, F.; Kolitsch, A.; Möller, W.

There is no abstract provided.

  • Lecture (Conference)
    PSE2004, 13.-17.09.2004, Garmisch-Partenkirchen, Germany

Permalink: https://www.hzdr.de/publications/Publ-9815
Publ.-Id: 9815


On the synthesis of fullerene-like CNx by IBAD: role of film-forming species, ion bombardment and film growth rate

Abrasonis, G.; Gago, R.; Vinnichenko, M.; Mücklich, A.; Kreissig, U.; Kolitsch, A.; Möller, W.

There is no abstract provided.

  • Lecture (Conference)
    PSE2004, 13.-17.09.2004, Garmisch-Partenkirchen, Germany

Permalink: https://www.hzdr.de/publications/Publ-9814
Publ.-Id: 9814


Organometallic technetium-99m RGD-peptide conjugates with tunable lipophilicity

Künstler, J.-U.; Seidel, G.; Decristoforo, C.; Haubner, R.; Giglio, J.; Leon, E.; Rey, A.; Pietzsch, H.-J.

Introduction:

Radiolabeled RGD-peptides have been studied for in vivo targeting of integrin receptors which are over-expressed in carcinomas [1]. The high pharmacological influence of the radiometal complex and limitations of various labelling concepts are reasons for exploring new approaches. The so-called “4+1” mixed-ligand chelate system, [Tc(NS3)(CN-R)], is an interesting alternative due to high labelling efficiency and in vivo stability [2]. Here we present the application of this concept to the labelling of the peptide c(RGDyK).

Experimental:

The figure shows the labelled peptides, corroborated upon coinjection with the corresponding rhenium compounds. The RGD-peptide, serving as monodentate ligand, was functionalized with 4-(isocyanomethyl)benzoic acid (L1) and 4-isocyanobutanoic acid (L2). 99mTc labelling was performed starting from 99mTc-EDTA followed by ligand exchange reaction with a mixture of the appropriate isocyanide-modified peptide and a tetradentate ligand (NS3R). The resulting series of 99mTc peptide conjugates [99mTc(NS3R)(L-c(RGDyK))] with R = R1, R2, R3 and L = L1, L2 was evaluated in biodistribution studies using tumour-bearing mice.

Results and Discussion:

The radiochemical yield was about 60 % after labelling 0.05-0.1 mg of isocyanide-modified peptide. Purification by HPLC resulted in radiochemical purity > 95 %. The stability of the 99mTc conjugates in PBS was higher than 90 % after 24 h. Distribution ratios (logD, octanol/PBS, pH 7.4) covered the range from -0.59 ± 0.14 for [99mTc(NS3R1)(L1-c(RGDyK))] to -3.3 ± 0.2 for [99mTc(NS3R3)(L2-c(RGDyK))]. The compounds exhibited only low tumour uptake and a fast hepatobiliary elimination. Substitution of the tripodal chelator bearing R1 or R2 by the carboxyl group-bearing ligand NS3R3 resulted in a predominant urinary excretion.

Conclusion:

The "4+1" mixed-ligand approach enables the 99mTc-labelling of c(RGDyK). The chelate unit dominates the biodistribution profile which could be influenced by varying the tripodal chelator.

[1] Haubner, R., Wester, H.-J. Curr. Pharm. Design 10 (2004) 1439-1455.
[2] Seifert, S. et al., Bioconjugate Chem. 15 (2004) 856-863.

IAEA, CSIC, FMP-CHLCC, Lab. de vacunas recombinantes, Fac. de Medicina, Uruguay for financial support.

Keywords: Tc '4+1' Complexes; Tc-Labeled Peptide; RGD Peptide; Isocyano-Modified Peptide

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S226
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9813
Publ.-Id: 9813


Determination of In concentration in InGaAs/GaAs epilayers in the early state of anisotropic stress relaxatio

Sass, J.; Mazur, K.; Eichhorn, F.; Strupinski, W.; Turos, A.

Kein Abstract vorhanden.

  • Lecture (Conference)
    Int. Conf. on Experimental and Computing Methods in High Resolution Diffraction Applied for Structure Characterization of Modern Materials, 13.-17.06.2004, Zakopane, Poland

Permalink: https://www.hzdr.de/publications/Publ-9812
Publ.-Id: 9812


Family of Equations of State Based on Lattice QCD: Impact on Flow in Ultrarelativistic Heavy-Ion Collisions

Bluhm, M.; Kämpfer, B.; Schulze, R.; Seipt, D.; Heinz, U.

We construct a family of equations of state within a quasiparticle model by relating pressure, energy density, baryon density and susceptibilities adjusted to first-principles lattice QCD calculations. The relation between pressure and energy density from lattice QCD is surprisingly insensitive to details of the simulations. Effects from different lattice actions, quark masses and lattice spacings used in the simulations show up mostly in the quark-hadron phase transition region which we bridge over by a set of interpolations to a hadron resonance gas equation of state. Within our optimized quasiparticle model we then examine the equation of state along isentropic expansion trajectories at small net baryon densities, as relevant for experiments and hydrodynamic simulations at RHIC and LHC energies. We illustrate its impact on azimuthal flow anisotropies and transverse momentum spectra of various hadron species.

Permalink: https://www.hzdr.de/publications/Publ-9811
Publ.-Id: 9811


Fluorine-18 radiolabeling of S100/calgranulins: a potential approach for characterization of receptors for advanced glycation endproducts in vivo

Hoppmann, S.; Haase, C.; Schwietzke, U.; Wüst, F.; Steinbach, J.; Pietzsch, J.

Introduction:

The interaction of S100/calgranulins, a multigenic family of Ca2+-modulated proteins, with receptors for advanced glycation endproducts, e.g., RAGE and AGERs, is hypothesized to be of high relevance in the pathogenesis of various diseases including cardiovascular diseases, inflammatory processes, and cancerogenesis. However, data concerning the role of circulating S100/calgranulins in these pathologies are scarce. Furthermore, it is currently not known whether RAGE or AGERs are universal S100/calgranulin receptors in vivo. One reason for this is the shortage of suitable radiolabeling methods for direct assessment of metabolic pathways of S100/calgranulins in vivo. We report a novel radiotracer approach using radiolabeling of recombinant human S100A1 with fluorine-18 (18F) and the application of 18F-labeled S100A1 (18F-S100A1) in dynamic small animal positron emission tomography (PET) studies in rats.

Experimental:

Human S100A1 was cloned in the bacterial expression vector pGEX-6P-1 and expressed in E. coli strain BL21. Radiolabeling of purified S100A1 was performed by conjugation with N-succinimidyl-4-(18F)fluorobenzoate ([18F]SFB). 18F-S100A1 was used for investigations of stability in vitro and in vivo. The metabolic fate of 18F-S100A1 in rats in vivo was delineated by dynamic PET studies using a dedicated small animal PET system.

Results and Discussion:

Radiolabeling of S100A1 with [18F]SFB at pH 7.4 resulted in 18F-S100A1 specifically labeled at the N-terminal glycine residue with radiochemical yields of 2-6% (decay-corrected) and effective specific activities of 0.5-1 GBq/µmol, respectively. In vitro experiments, and biodistribution and metabolite studies in rats in vivo revealed high stability for the 18F-S100A1. The organ-specific in vivo distribution and kinetics of 18F-S100A1 correlated well with the anatomical localization of receptors for advanced glycation endproducts, e.g., in blood vessels and lungs. In the presence of glycated human low density lipoprotein (glycLDL), a well characterized RAGE ligand, mean plasma residence time of 18F-S100A1 increased by 40% from 29.6±1.5 min to 41.3±2.1 min and lung associated retention of 18F-S100A1 decreased by 57% first indicating circulating S100A1 to be a specific ligand for receptors for advanced glycation endproducts in rats in vivo. Data were compared to former small animal PET studies using the 18F-labeled glycLDL.

Conclusion:

Radiolabeling of S100/calgranulins with 18F and the use of small animal PET provides novel probes to delineate functional expression of RAGE and AGERs under normal and pathophysiological conditions in rodent models of disease in vivo.

Acknowledgement: This study was supported in part by the DFG (grant no. Pi 304/1-1).

Keywords: S100 Proteins; Small Animal PET; Inflammation; Cancerogenesis; Receptors for Advanced Glycation End Products

  • Lecture (Conference)
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S28
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9810
Publ.-Id: 9810


[18F]FBAM and [18F]FBOM: novel prosthetic groups for the mild labeling of thiol group-containing biomacromolecules

Vogler, L.; Berndt, M.; Pietzsch, J.; Wüst, F.

Introduction:

The incorporation of 18F into peptides and proteins usually takes advantage of prosthetic groups, also referred to as bifunctional labeling agents. This approach comprises 18F incorporation into a small organic molecule capable of being linked to peptides and proteins under mild conditions. This work deals with a comparative discussion on the synthesis and application of N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]-maleimide ([18F]FBAM) and 4-[18F]fluorobenzaldehyde-O-(2-{2-[2-(pyrol-2,5-dion-1-yl)ethoxy]ethoxy}ethyl)oxim ([18F]FBOM) as novel prosthetic groups for the mild and selective conjugation to thiol group-containing biomacromolecules (Fig. 1).

Experimental:

The aminooxy-functionalized labeling precursor for radiosynthesis of [18F]FBAM was prepared in a convenient three-step synthesis sequence in a total yield of 59%. The corresponding labeling precursor for the radiosynthesis of [18F]FBOM succeeded in a four-step reaction sequence in 14% total yield. Formation of the prosthetic groups [18F]FBAM and [18F]FBOM was achieved through condensation reaction with [18F]fluorobenzaldehyde to form the desired oximes in radiochemical yields of 20-30% ([18F]FBAM) and of 14-19% ([18F]FBOM), respectively.

Results and Discussion:

The syntheses were carried out in a remotely-controlled radiofluorination module allowing the convenient and reliable performance of the radiolabeling reactions. The radiochemical purity exceeded 95% and the specific activity ranged from 50 to 80 GBq/µmol. The total synthesis time was 70 to 80 min. The lipophilicity was determined to be logP=2.71 for [18F]FBAM and logP=0.84 for [18F]FBOM. The usefulness of [18F]FBAM and [18F]FBOM as thiol-reactive group prosthetic group was demonstrated by the reaction with glutathion, low density lipoproteins (LDL) and modified neurotensin derivatives. Reaction of [18F]FBAM and [18F]FBOM with glutathione showed that the use of as little as 1 µg/ml glutathione after 30 min provides excellent radiochemical yields of 95% of the desired coupled products. Labeling of LDL showed superior results with [18F]FBAM, whereas comparable results for both prosthetic groups were obtained for the labeling of modified neurotensin derivatives.

Conclusion:

The ease of production and the excellent performance in radiolabeling reactions make compounds [18F]FBAM and [18F]FBOM very promising prosthetic groups for the mild and selective conjugation to thiol group-containing biomacromolecules.

Keywords: Prosthetic Group; 18F-Labeling; Maleimide

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S117
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9809
Publ.-Id: 9809


68Ga-, 86Y- and 111In-radiolabeled anti-tenascin-C oligonucleotide aptamers as a potential probe for tumor imaging

Friebe, M.; Hecht, M.; Borkowski, S.; Seifert, S.; Noll, B.; Wüst, F.; Stephens, A. W.; Hilger, C. S.; Bergmann, R.; Johannsen, B.; Dinkelborg, L. M.

Introduction:

The matrix protein tenascin-c (TN-C) represents an interesting target for molecular imaging in oncology due to it´s high abundance in a variety of human tumors such as lung, breast and brain tumors [1]. First radiolabeled anti-TN-C antibodies could successfully proof the concept of tumor-TN-C targeting [2]. However, a persistently high blood level hampers their use for targeted imaging. Aptamers, a class of rapidly clearing high affinity oligonucleotides, have been introduced successfully to molecular imaging by the application of the Tc-99m labeled TN-C Targeting Aptamer-1 (TTA-1) [3]. Here we report on the radiolabeling, binding affinity and biodistribution of this novel targeting aptamer labeled with metal PET isotopes.

Experimental:

Labeling with Ga(III), Y(III), and In(III) was performed in a one pot reaction after conjugation of a DOTA-type chelating moiety to TTA-1-MAG2. In-111 was included in the study as a surrogate for Ga and Y in long term stability and affinity tests. The labeling was carried out in the presence of the aptamer-chelator conjugate and the respective radiometal in acetate buffer. Degradation was investigated in human plasma employing PAGE. Affinity for human TN-C was determined in a nitrous cellulose filter binding assay. Athymic mice, bearing the human U251 tumor cell line, were injected with the radiolabeled TTA-1 derivatives.

Results and Discussion:

Addition of the radiometal salts yielded the respective labeled aptamer conjugates in high yields (60 – 80 %). Ultrafiltration of the products led to > 95 % of pure material as determined by PAGE and HPLC methods. The biological stability in human plasma ranged from 68 % (In-111) to 95 % (Y-86) of intact material after 6 hr. Binding affinity for human TN-C revealed a KD of 1 nM (In-111). A maximum tumor uptake of 2.0 % ID/g (Ga-68), 1 hr p.i. and T/Non Tumor ratios of 5.1 (T/blood), 0.2 (T/kidney), 0.7 (T/liver) 1 hr p.i. proved to be adequate to image the U251 tumor xenograft in mice. Tumor visualization was possible for both Ga-68 and Y-86 labeled TTA-1.

Conclusion:

The introduction of a DOTA-type chelating moiety could be successfully used to radiolabel the aptamer probe with In, Ga and Y. The stability against nuclease degradation along with a significant tumor accumulation, high T/ blood levels and the imaging capabilities in PET-scans make these compounds promising candidates for further evaluation as multi-tumor imaging agents.

Acknowledgement:

1. R. Chiquet-Ehrismann, Cell 47, 131 (1986)
2. P. Riva, Cancer 73, 1076 (1994)
3. B.J. Hicke, J. Nuc. Med. 47, 668-678 (2006).

Keywords: Aptamers; Oligonucleotides; PET; Ga-68; Tumor Targeting

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S387
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9808
Publ.-Id: 9808


Radiolabeling of multimeric neurotensin(8-13) analougues with the short-lived positron emitter fluorine-18

Hultsch, C.; Berndt, M.; Bergmann, R.; Wüst, F.

Introduction:

Neurotensin receptors are expressed with high incidence in several human tumour entities. Thus, radiolabeled neurotensin derivatives might be used for tumour targeting. However, its application is limited by insufficient metabolic stability. Metabolic stability might be improved by the synthesis of multimeric peptides.

Experimental:

Three methods for 18F-labeling of dimeric and tetrameric neurotensin(8-13) derivatives were evaluated with respect to the labeling yield and the required peptide amounts.

Results and Discussion:

Labeling using N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) gave low radiochemical yield for the dimeric peptides. Coupling of the tetramer with [18F]SFB was not successful. Furthermore, labeling of aminooxy-functionalized neurotensin(8-13) derivatives using 4-[18F]fluorobenzaldehyde ([18F]FBA) was investigated. High yields of up to 96% were obtained for the dimer whilst coupling of the tetramer only gave low yields of up to 10%.
In contrast to these findings, labelling of sulfhydryl-functionalized neurotensin(8-13) derivatives using the maleinimide 4-[18F]fluorobenzaldehyde O-[6-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-hexyl]-oxime ([18F]FBAM) resulted in high radiochemical yields for both, the dimer and the tetramer, being 94% and 40%, respectively. Therefore, [18F]FBAM seems to be the most suitable 18F-labeling agent for multimeric neurotensin(8-13) derivatives. The synthesized 18F-labeled multimeric neurotensin derivatives are depicted in Fig. 1.

Conclusion:

In summary, 18F-radiolabeling of dimeric and tetrameric NT(8-13) derivates was investigated. Suitable results were obtained by labeling of the sulfhydryl-functionalized peptides using [18F]FBAM. Using [18F]SFB or [18F]FBA as the labeling agent gave only low radiochemical yields. Furthermore, labeling of the dimer gave better radiochemical yields than labeling of the tetramer – independent from the labeling method which was used. Therefore, the nature of the peptide exhibits a strong influence on the coupling reaction.

Keywords: Neurotensin; Fluorine-18; Tumor Targeting; Multimer

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S118
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9807
Publ.-Id: 9807


Synthesis of 18F-labeled neurotensin(8-13) via copper-mediated 1,3-dipolar [3+2]cycloaddition reaction

Wüst, F.; Ramenda, T.; Bergmann, R.

Introduction:

Click chemistry is a generic term for a set of reactions, which make use of several selective and modular building blocks to create heteroatom C-X-C links. The copper(I)-catalyzed 1,2,3-triazole formation from azides and terminal acetylenes according to a 1,3-dipolar [3+2]cycloaddition is a particularly powerful linking reaction due to its high degree of specificity and the biocompatibility of the reactants. Recently the first application of click chemistry in 18F chemistry has been reported [1]. Herein we report an alternative click chemistry strategy suitable for 18F labeling reactions.

Experimental:

The labeling strategy was exemplified by the synthesis of 18F-labeled neuropeptide neurotensin NT(8-13) [18F]3 (Fig. 1).
Results and Discussion: 4-[18F]Fluoro-N-(prop-2-ynyl)benzamide [18F]2 as novel terminal alkyne building block was prepared in 90% radiochemical yield by the reaction of readily available N-succinimidyl-4-[18F]fluorobenzoate [18F]SFB with propargyl amine. Purification of [18F]2 was performed by solid phase extraction. Coupling of 18F-labeled terminal alkyne with azide-functionalized NT(8-13) 1 gave the corresponding 18F-labeled NT(8-13) derivative [18F]3 in 66% yield as determined by radio-HPLC. Receptor binding of NT(8-13) derivative [19F]3 was investigated using the human colon adenocarcinoma cell line HT-29. The peptides inhibited the binding of [3H]-NT, showing a typical sigmoid curve. The in vitro binding affinity of NT(8-13) derivative [19F]3 was determined to be 66 nM.

Conclusion:

In summary, the use of [18F]fluoro-N-(prop-2-ynyl)benzamide [18F]2 as suitable click chemistry building block allows the convenient radiolabeling of 18F-labeled small molecular weight compounds as well as peptides as exemplified for the synthesis of 18F-labeled NT(8-13) [18F]3. This offers the application of click chemistry to the synthesis of a broad array of novel 18F-labeled compounds.
References:
[1] J. Marik, J.L. Sutcliffe, Tetrahedron Lett. 47 (2006) 6681-6684.

Keywords: Click Chemistry; 18F-Labeling; PET

  • Lecture (Conference)
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S38
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9806
Publ.-Id: 9806


FZD research activities for VVER NPPs

Rindelhardt, U.

Within the framework of reactor safety research of the German Federal Ministry of Economics, the scientific-technical cooperation of selected topics with Russian institutions is supported. Some of these topics are performed by the Institute of Safety Research of the Forschungszentrum Dresden-Rossendorf (FZD) together with Russian institutes. The paper summarizes selected results for the following topics:

• Contribution to the validation of the Russian thermalhydraulic code KORSAR
• Safety analysis for VVER Reactors
• 3D fluiddynamic calculations
• Neutron embrittlement of RPV vessels
• Validation of neutron fluence calculations
• Post operation investigation of RPV material from Greifswald NPP
• Neutron dosimetry of VVER 1000

Keywords: Reactor safety research; VVER

  • Invited lecture (Conferences)
    Best Practice Seminar COVERS, 20.-22.06.2007, Madrid, Spain

Permalink: https://www.hzdr.de/publications/Publ-9805
Publ.-Id: 9805


The (224) asymmetrical reflection from laterally patterned heteroepitaxial inGaAs/GaAs layers

Mazur, K.; Sass, J.; Eichhorn, F.; Strupinski, W.; Turos, A.; Kowalik, A.

Kein Abstract vorhanden.

  • Lecture (Conference)
    Int. Conf. on Experimental and Computing Methods in High Resolution Diffraction Applied for Structure Characterization of Modern Materials, 13.-17.06.2004, Zakopane, Poland

Permalink: https://www.hzdr.de/publications/Publ-9804
Publ.-Id: 9804


In-situ studies of Ni-Ti thin films

Martins, R. M. S.; Braz Fernandes, F. M.; Silva, R. J. C.; Beckers, M.; Schell, N.

Kein Abstract vorhanden.

  • Lecture (Conference)
    Shape Memory and Superelastic Technology SMST-Europe, 03.-07.10.2004, Baden-Baden, Germany

Permalink: https://www.hzdr.de/publications/Publ-9803
Publ.-Id: 9803


Radiosynthesis and radiopharmacological charakterization of n.c.a. sodium [18f]fluoroacetate in tumor bearing mice

Bergmann, R.; Richter, S.; Wüst, F.

Introduction:

[18F]Fluoroacetate is discussed as an alternative to the well-established PET radiotracer [11C]acetate for the diagnosis and treatment monitoring of prostate cancer. The first automated synthesis of [18F]fluoroacetate was reported very recently by Sun and co-workers [1]. Herein we describe an alternative convenient remotely-controlled synthesis of no-carrier-added sodium [18F]fluoroacetate and its radiopharmacological evaluation in tumor bearing mice.

Experimental:

Three ethyl esters and three tert.-butyl esters containing either a methanesulfonyloxy- (OMs), p-toluenesulfonyloxy- (OTs) or p-nitrobenzene-sulfonyloxy (ONs) leaving group were investigated as labeling precursors.

Results and Discussion:

The optimized radiosynthesis of n.c.a. sodium [18F]fluoroacetate was performed in two steps: (1) Incorporation of fluorine into (methanesulfonyloxy)-acetic acid tert.-butyl ester 1 as the superior labeling precursor in acetonitrile at 100°C for 5 min followed by (2) acidic hydrolysis of the resulting [18F]fluoroacetic acid tert.-butyl ester at 100°C for 10 min to afford [18F]fluoroacetic acid. Several consecutive purification steps using anion exchange cartridges (Alltech Maxi-Clean SAX) and Sep-Pak neutral alumina cartridges gave sodium [18F]fluoroacetate in very reproducible radiochemical yields (20-25%, decay-corrected, n=20) in high radiochemical purity (>95%) within 50 min (Fig. 1).
Radiopharmacological studies were performed using rats and tumor bearing mice. Metabolism studies in arterial blood showed no metabolites after 60 min p.i. [18F]Fluoroacetate was readily accumulated in HT-29 tumors (tumor/muscle 1.75 ± 0.20 mean ± SEM, n=6) as shown in small animal PET studies (Fig. 2).

References: [1] L.-Q. Sun et al. Nucl. Med. Biol., 2006, 33, 153-158.

Conclusion:

The robust and reproducible remotely-controlled two step/one pot synthesis of [18F]fluoroacetate starting from readily available (methanesulfonyloxy)-acetic acid tert.-butyl ester 3a as a novel labelling precursor represents an alternative to the published procedures. A comparing discussion of data obtained with [11C]acetate in rats and mice will be presented.

Keywords: 18F-Labeling; [18F]Fluoroacetate

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S466
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9802
Publ.-Id: 9802


Synthesis, biodistribution and metabolite analysis of different [86Y]DOTA-L-RNA oligonucleotides in rats

Schlesinger, J.; Koezle, I.; Bergmann, R.; Klussmann, S.; Wüst, F.; Pietzsch, H.-J.; Steinbach, J.

Introduction:

Mirror-image oligonucleotides are constructed of an L-configured ribose or deoxyribose. This modification leads to an extraordinary high metabolic stability against enzymatic degradation in biological environments. The radiolabeling of an L-oligonucleotide with the positron emitter 86Y (t1/2 = 14.7 h) is done via the bifunctional chelator approach. The influence of two different [86Y]DOTA chelates on the radiopharmacological properties of [86Y]DOTA-L-oligonucleotides was investigated with an L-RNA 12mer 1 (sequence: 5'-Aminohexyl UGA CUG ACU GAC-3' MW 3975). Both 86Y-labeled L-RNAs 3a, 5a were characterized by a comparative biodistribution study in Wistar rats and metabolite analyses.

Experimental:

The amine functionality of the 5'-hexylamine modified L-RNA 1 was used for conjugations with DOTA-NHS ester 2 and (S)-p-SCN-bz-DOTA 4, accomplished in the formation of a selective amide bond 3 and thiourea bond 5, respectively. After 86Y-labeling of 3 and 5 biodistribution studies were performed for each compound 3a, 5a with eight Wistar rats.

Results and Discussion:

Both DOTA-modified L-RNAs 3, 5 were radiolabeled with 86Y(III) (QSA Global, Germany) with radiochemical yields of 76 % and 85 %, respectively. High renal excretions were found for both 86Y-labeled L-RNAs 3a, 5a whereas differences in the retention were observed for the radiolabeled compounds in the kidneys and the adrenal glands. The standardized uptake value (SUV) of compound 3a in the kidneys reached 10 ± 2.0 after 5 min and decreased to 6.1 ± 0.53 after 60 min. For compound 5a the SUV in the kidneys increased from 13 ± 1.6 after 5 min to 14 ± 1.1 after 60 min. Remarkably high SUVs (3.5 ± 0.48 and 3.2 ± 0.33) were also observed in the adrenal glands after 60 min for both compounds. The SUVs in other organs were below 1.0 after 60 min for 3a and 5a in this study. Over 85% intact 3a and 5a were found in urine samples of Wistar rats 60 min after application of 3a, 5a as confirmed by Radio-HPLC.

Conclusion:

Differences in the kidney excretion profile of 3a and 5a indicate an influence of the different chemical attachments of the [86Y]DOTA chelates to L-RNA 1. The high metabolic stability of the L-RNA suggests the potential of L-oligonucleotides as molecular probes for PET.

Acknowledgement: This work was supported by the EU-FP6 integrated project BioCare contract no.: 505785.

Keywords: 86Y; DOTA; L-RNA; Oligonucleotides

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S462
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9801
Publ.-Id: 9801


In-situ X-ray diffraction during sputtering of Shape Memory Alloy (SMA) Ni-Ti thin films

Martins, R. M. S.; Braz Fernandes, F. M.; Silva, R. J. C.; Schell, N.

Kein Abstract vorhanden.

  • Lecture (Conference)
    DPG-Frühjahrstagung, 08.-12.03.2004, Regensburg, Germany

Permalink: https://www.hzdr.de/publications/Publ-9800
Publ.-Id: 9800


Gallium-68 complexes with tripodal NS3 ligands: in vitro and in vivo stability studies

Noll, B.; Schiller, E.; Kraus, W.; Bergmann, R.; Pietzsch, H.-J.

Introduction:

We report on formation and structures of 68Ga '4+1' complexes, [Ga(NS3)R], with the tripodal ligand tris(2-mercaptoethyl) amine (NS3) and water or secondary amines as co-ligands (R). To improve the bio-behavior of such compounds new hydrophilic NS3 chelators have been introduced. Challenge experiments with transferrin have been performed to study the influence of the co-ligand on the in vitro stability of the gallium complexes. Their in vivo stability was evaluated in the rat using HSA microspheres.

Experimental:

68Ga was eluted from a 68Ge/68Ga generator (Obninsk, Russia) as GaCl3 in hydrochloric solution (0.1 M) and added to the aqueous solution of the oxalate salt of the NS3 ligand in presence of the corresponding amine. Ga complexes were formed in aqueous solution at ambient temperature. Challenge experiments were carried out at 37°C with the plasma protein transferrin (5 mg/ml), the exchange was controlled by thin layer chromatography on silicagel (Merck) and methanol as eluent.

Results and Discussion:

The labelling procedure with 68Ga generator eluate runs in high yield under weakly alkaline conditions within some minutes. It is not necessary to heat the reaction mixture so that sensitive molecules can also be labelled. Challenge experiments with apotransferrin were carried out for several hours. Amine-coordinated complexes as well as non-amine compounds showed high in vitro stability within 240 minutes. The in vivo stability of the complexes was evaluated in the rat using HSA microspheres. 68Ga-labelled HSA microspheres were completely accumulated in the lung. In small animal PET studies no significant loss of 68Ga activity was observed within three hours.

Conclusion:

The '4+1' mixed-ligand approach enables the 68Ga-labelling of biomolecules under physiological conditions. The lipophilicity of the complexes can be controlled by introducing pharmacological modifiers (e.g. PEG, glucosamine, crown ether) into the tetradentate ligand and/or derivatization of the monodentate ligand. Moreover, the described approach allows the functionalization of a biomolecule with the tripodal as well as with the monodentate ligand.

Keywords: Gallium Complexes; Tripodal Ligand; In Vitro Stability; In Vivo Stability; Tris(2-Mercaptoethyl) Amine

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S244
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9799
Publ.-Id: 9799


Experimental hypoxia as a potent stimulus for radiotracer uptake in vitro: comparison of different tumor cells and primary endothelial cells

Treite, F.; Oswald, J.; Mäding, P.; Schwenzer, B.; Bergmann, R.; Pietzsch, J.

Introduction:

Hypoxia is a common feature of solid malignant tumors. The vascular endothelial growth factor (VEGF) is upregulated by hypoxia inducible factors (HIFs) as a result of central hypoxia and plays an outstanding role for the formation of new tumoral blood vessels by promoting proliferation and migration of endothelial cells. Beside [18F]fluorodeoxyglucose (18F-FDG) as standard radiotracer for tumor imaging with PET, oxygenation status in experimental and human tumors can be visualized by using [18F]fluoromisonidazole (18F-FMISO).

Experimental:

The aim of our study was the evaluation of the uptake of the radiotracers 18F-FDG and 18F-FMISO under standardized hypoxic conditions in various primary endothelial cells compared with three tumor cell lines in vitro. Experimental hypoxia was characterized by measurement of expression of HIF-1α, VEGF and various VEGF receptors by quantitative real-time PCR.

Results and Discussion:

Experimental hypoxia was confirmed by significant upregulation of characteristic hypoxia-related genes like VEGF in all analyzed primary endothelial cells and the tumor cell lines. VEGF receptors 1, 2 and 3 were almost absent in tumor cells and only expressed in endothelial cells. In contrast, the VEGF co-receptor Neuropilin-1 showed an increased expression in tumor cells under experimental hypoxia. In comparison to normoxic conditions, cellular uptake of 18F-FDG was significantly increased under experimental hypoxia in both tumor and endothelial cells. Otherwise, uptake of 18F-FMISO was always higher in tumor cells than in endothelial cells under hypoxic conditions.

Conclusion:

Our data showed a strong dependence of 18F-FDG uptake on the availability of oxygen in vitro. The study demonstrates relevance of endothelial cells as one important part of the tumor microenvironment under hypoxic conditions. This may have implications when performing PET studies aiming at the visualization and characterization of highly vascularized tumors, in particular, when using 18F-FDG.

Keywords: 18F-FMISO; 18F-FDG; Vascular Endothelial Growth Factor

  • Poster
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S421
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9798
Publ.-Id: 9798


In-situ XRD during sputtering of Shape Memory Alloy (SMA) Ni-Ti thin films

Martins, R. M. S.; Braz Fernandes, F. M.; Silva, R. J. C.; Beckers, M.; Schell, N.

Kein Abstract vorhanden.

  • Lecture (Conference)
    14th ESRF User Meeting, 10.-11.02.2004, Grenoble, France
  • Lecture (Conference)
    ESRF Science Days, 26.-28.05.2004, Aussois, France

Permalink: https://www.hzdr.de/publications/Publ-9797
Publ.-Id: 9797


Short-wavelength (lambda < 4 micrometer) intersubband transitions and quantum cascade lasers in InP-based material systems

Helm, M.

no abstract available
Short-wavelength intersubband transitions and quantum cascade lasers in InP-based material systems

Keywords: quantum cascade laser; infrared

  • Lecture (others)
    Seminarvortrag am Deptartment of Electrical Engineering, Princeton University, 26.02.2004, Princeton, NJ, USA

Permalink: https://www.hzdr.de/publications/Publ-9796
Publ.-Id: 9796


X-ray grazing incidence diffraction: A tool to optimize focused ion beam implantation

Grenzer, J.; Bischoff, L.; Pietsch, U.

Kein Abstract vorhanden.

  • Lecture (Conference)
    7th Biennial Conf. on High Resolution X-Ray Diffraction and Imaging, 07.-10.09.2004, Prague, Czech Republic

Permalink: https://www.hzdr.de/publications/Publ-9795
Publ.-Id: 9795


Silicon light-emitting pn diodes

Helm, M.

no abstract available
Silicon light-emitting pn diodes

Keywords: light emitter; silicon

  • Lecture (others)
    Seminarvortrag am Department of Electrical Engineering, Princeton University, 11.02.2004, Princeton, NJ, USA

Permalink: https://www.hzdr.de/publications/Publ-9794
Publ.-Id: 9794


Annealing of ITO films: in situ studies of structure and resistance

Cantelli, V.; Rogozin, A.; Shevchenko, N.; Vinnichenko, M.; Prokert, F.; Kolitsch, A.; Möller, W.

Kein Abstract vorhanden.

  • Lecture (Conference)
    ESRF Science Days, 26.-28.05.2004, Aussois, France

Permalink: https://www.hzdr.de/publications/Publ-9793
Publ.-Id: 9793


Re-188 complexes with tetradentate S4 ligands derived from MESO-DMSA for labeling of biomolecules

Seifert, S.; Jentschel, C.; Bergmann, R.; Steinbach, J.; Pietzsch, H.-J.

Introduction:

Various Tc and Re chelates are currently under investigation for stable labeling of biomolecules. Unfortunately, most of the 188Re chelates degrade more rapidly than the 99mTc analogues which is limiting the further development of rhenium-based therapeutic agents. To overcome this problem, we developed a tetradentate S4 ligands derived from DMSA [1].

Experimental:

Labeling. To a kit vial, containing 5 mg oxalic acid, 5 mg γ-cyclodextrin, 5 mg ascorbic acid and 0.01 - 0.05 mg Sn-S4 complex, 1.0 ml of perrhenate eluate (50–500 MBq) was added. After heating at 50 °C for 60' the yield was 90 – 93% (HPLC and TLC). For stability and biodistribution studies the isomers were separated by semi-preparative HPLC. The identity of the species obtained was confirmed by comparison with the HPLC profiles of fully characterized reference 185/187Re analogues.
Biodistribution: Male Wistar rats (5 – 6 weeks old), 0.5 ml of the 188Re complex solution (0.5 MBq) was injected into the tail vein under slight ether anesthesia. After the injection, the rats were sacrificed by heart puncture 5 min and 60 min post injection.

Results and Discussion:

A kit formulation was developed which contains only microgram amounts of the S4 ligand stabilized in the form of a stannous complex. Several isomers were separated by HPLC from the preparation solutions and characterized in vitro and in vivo. All of them were absolutely stable in rat and human plasma solutions. Challenge experiments with cysteine corroborated the high inertness of the isomers towards ligand exchange reactions. Samples of blood, intestine and urine of rats confirmed the high in vivo stability of the 188Re complexes. Biodistribution studies resulted in a high uptake and fast clearance from the liver of the more lipophilic cis and trans isomers of complex I (logDo/w 1.5 - 1.7), whereas the hydrophilic isomers of complex II (logDo/w about -1.75) were preferentially excreted via the renal pathway. The low level of radioactivity in the stomach indicated good in vivo stability too.

Conclusion:

The 188Re-S4 complexes offer the possibility of stable and high specific activity labeling of biomolecules. Their charge and lipophilicity may be controled by various possibilities to introduce functional groups. The amine group of the bridging framework makes available a position for coupling biomolecules.

[1] S. Seifert et al., Bioconjugate Chem. 2006, 17, 1601-1606.

Keywords: Rhenium-188 Complexes; Bridged DMSA Ligand; Tetrathiol Ligand; Stability; Radiotherapy

  • Lecture (Conference)
    17th International Symposium on Radiopharmaceutical Sciences, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S10
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9792
Publ.-Id: 9792


Growth of sputter-deposited Ti1-xAlxN investigated by in-situ x-ray diffraction

Beckers, M.; Schell, N.; Martins, R. M. S.; Möller, W.

Kein Abstract vorhanden.

  • Lecture (Conference)
    Symp. of the Belgium and Dutch Vacuum Society, 09.-10.12.2004, Gent, Belgium

Permalink: https://www.hzdr.de/publications/Publ-9791
Publ.-Id: 9791


86Y-labelled human serum albumin microspheres (DOTA-HSAM): In vivo stability depends on surface structure of the spheres

Schiller, E.; Pietzsch, H.-J.; Bergmann, R.; Pietzsch, J.; Noll, B.; Sterger, A.; Wunderlich, G.

Introduction:

Radiolabelled particles are an attractive tool in the therapy of malignancies of the liver. We consider particles manufactured from denatured human serum albumin (HSAM) as useful carriers of therapeutic radionuclides, e.g. Y-90.

Experimental:

Two batches of HSAM (ROTOP Pharmaka GmbH; diameter: 20 – 30 μm) with smooth or rough surface, as determined by REM, were used for our studies. HSAM were functionalized by coupling DOTA via its isothiocyanate derivative in aqueous solution at pH 8.5 to lysine ε-amino groups on the surface of the spheres. Stability of Y-86 labelled DOTA-HSAM was investigated both in vitro (DTPA challenge) and in vivo (i. v. injection into the tail vein of healthy Wistar rats).

Results and Discussion:

Approximately 25 DOTA molecules per molecule HSA could be attached as estimated from elemental analysis of DOTA-HSAM. Y-86 labelling was performed under optimized conditions in 96 ± 1 % yield. No significant differences between smooth- and rough-surfaced HSAM were found for both, DOTA coupling and Y-86-labelling. In DTPA challenge experiments 98 ± 0 % of the radioactivity were still particle-associated after 24 hours incubation at 37 °C. In the in vivo experiments radiolabelled smooth and rough microspheres were completely trapped in the lungs. After 48 h the two batches differed significantly in their biodistribution pattern. For the clearance of radioactivity from the lungs decay-corrected half-lives of 85 h (rough microspheres) and 187 h (smooth microspheres) were calculated.

Conclusion:

For the preparation of HSA-derived microspheres for radiotherapeutic application smooth-surfaced spheres are superior to rough spheres due to their higher in vivo stability.

  • Poster
    17th International Symposium on Radiopharmceutical Scieneces, 30.04.-04.05.2007, Aachen, Deutschland
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007)Suppl. 1, S224
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9790
Publ.-Id: 9790


Repair kinetics of DNA double strand breaks induced in human mammary epithelial cells

Beyreuther, E.; Dörr, W.; Lessman, E.; Pawelke, J.

The introduction of mammography screening programs in some countries initiated a continuous discussion about the benefit or possible accompanied risk of the used radiation qualities. Contributing to this discussion we used different methods, such as clonogenic survival and the analysis of chromosomal aberrations by FISH, to study biological effects with the human mammary epithelial cell line 184A1, which is of interest especially for the induction of breast cancer. Radiation qualities applied were 10 and 25 kV soft X-rays and a 200 kV X-ray tube as reference radiation source. Furthermore, we develop these methods and investigate the repair kinetics of DNA double strand breaks (DSB) with cell line 184A1 to learn more about the underlying processes.
The DNA damage response, following irradiation, includes an efficient DSB recognition system as well as different DSB repair mechanisms. Important contributions to these processes are the phosphorylation of histone H2AX (gH2AX) and the localization and phosphorylation of the p53 binding protein 1 (53BP1) at the sides of DNA DSBs. Both molecules are essential for the recognition of DNA DSBs and hence for the induction of repair processes. Using appropriate antibodies, the phosphorylated molecules can be visualized as nuclear foci and their time-dependent formation can be followed after irradiation.
The time-dependent formation of gH2AX- and 53BP1-foci was used in the present work to investigate the induction and rejoining of DNA DSBs up to 48 hours after irradiation. Two different antibodies were used to visualize and quantify the foci induced by two different doses of 0.25 and 2 Gy of 25 and 200 kV X-rays, respectively.
The kinetics obtained after irradiations with 2 Gy show a similar shape and therefore energy independence for both energies, which can be explained by the same underlying repair processes. Shortly after irradiation the number of foci per cell shows a steep increase, resulting in a maximum after 2 hours and a subsequent 2-phase decrease. Although the position of the maximum is the same, the number of foci per cell differs for 25 kV and 200 kV X-rays, being 7.99 ± 0.12 and 6.19 ± 0.10, respectively. The rejoining of DSBs, deduced by the decrease of number of foci per cell can be divided in a first phase, which seems to be faster, and a slower second one. During the first phase, the number of foci per cell is reduced to about 50 % of the maximum and in the second phase they are reduced to the control level, whereas for 25 kV a significant number of foci per cell remain. These results implicate that, on the one hand, the number of the induced DNA DSBs is significantly higher for 25 kV X-rays and, that on the other hand, some DSBs remain unrepaired. These DSBs can influence the genomic integrity and can result in chromosomal aberrations.
First experiments for the irradiation with 0.25 Gy of 25 kV show the same shape as that with higher dose, but the maximum is derived at 30 minutes after irradiation. The maximum number of foci per cell was 4.03, which is about the half compared to a dose of 2 Gy with the same energy.

  • Poster
    10th International Wolfsberg Meeting, 12.-14.05.2007, Wolfsberg Conference Center, Ermatingen, Switzerland
  • Abstract in refereed journal
    Molecular Radiation Biology/Oncology 7(2007)
    ISSN: 3980881946
  • Poster
    Oncoray, Strategie-Meeting, 08.-09.01.2008, Gröditz, Germany

Permalink: https://www.hzdr.de/publications/Publ-9788
Publ.-Id: 9788


New measurements of physical properties of PbBi alloys

Plevachuk, Y.; Sklyarchuk, V.; Eckert, S.; Gerbeth, G.

Lead-bismuth alloys are under intense consideration as target material of spallation sources. The thermohydraulic design of such a target or related coolant systems requires a reliable data basis regarding the temperature dependent physical properties of such alloys. We present new measurements of the electrical conductivity and the thermoelectric power up to about one hundred degree above the melting point for various alloy compositions. For the eutectic alloy the measurements were performed up to a temperature of 1000 K including, in addition, viscosity, thermal conductivity and surface tension. A comparison with data and scaling relations available in literature will be given. New temperature scaling relations will be derived for each of those properties, which we recommend as input for thermohydraulic simulations.

  • Lecture (Conference)
    IV International Workshop on Materials for HLM cooled Reactors and Related Technologies, 21.-23.05.2007, Rom, Italy

Permalink: https://www.hzdr.de/publications/Publ-9787
Publ.-Id: 9787


European research on HLM thermal hydraulics for ADS applications

Roelofs, F.; Jager, B.; Class, A.; Jeanmart, H.; Schuurmans, P.; Ciampichetti, A.; Gerbeth, G.; Stieglitz, R.; Fazio, C.

The objective of the European 6th framework project EUROTRANS, is to demonstrate the technical feasibility of transmutation of high level nuclear waste using Accelerator Driven Systems (ADS). Within this objective the design of a European experimental ADS (XT-ADS) should demonstrate the technical feasibilities to transmute a sizeable amount of waste and to operate an ADS safely. The XT-ADS will be a subcritical reactor system having liquid lead-bismuth eutectic (LBE) as coolant.
This liquid LBE is also intended to serve as target material for the spallation reaction which forms a crucial part to the subcritical reactor core. Since LBE is used as core coolant and spallation material, knowledge of the thermal hydraulic behaviour of LBE is essential.
Within the DEMETRA domain of the EUROTRANS project, basic thermal hydraulic studies in order to support the design and safety analysis of XT-ADS components and the development of measurement techniques have been started. In particular, the work focuses on:
• Characterisation of the free surface flow for the windowless spallation target design.
Validated numerical methods are needed to predict the LBE heat removal capability in the windowless spallation target configuration. For this purpose, computational fluid dynamics (CFD) simulation methods are most appropriate. CFD methods allow to capture the specific three-dimensional local effects of the LBE free surface including the heat deposition.
Various methods are assessed and first promising results have been obtained for the simulation of an isothermal windowless spallation target. For the improvement and validation of the developed numerical models, an experimental campaign has started. This campaign exists of experiments in a water-loop and in an LBE loop.
• The interaction of LBE with water as secondary coolant.
Since the XT-ADS design foresees the presence of steam generator modules placed inside the main vessel in direct contact with the lead-bismuth and the probability of a steam generator tube rupture is not negligible, the consequences of such an accident have to be assessed. Experimental campaigns aim at assessing the physical effects and possible consequences related to the interaction of LBE and water in representative conditions for the XT-ADS design. The experimental data are also used for the validation of the SIMMER code. First experimental campaigns have been performed successfully. Simulation of the experimental data with the SIMMER code showed a good agreement.
• The development of measurement techniques for heavy liquid metal (HLM) flows.
Measurement techniques are developed for different purposes (i.e. thermal-hydraulics experiments and operational techniques for large facilities in relation to the development of the XT-ADS) and tested within the laboratories of FZD (Germany), FZK (Germany), and SCK•CEN (Belgium). The focus is on local velocity meters, integral flow meters, and free surface level sensors. The various methods studied are briefly described.

Finally, the links with the DESIGN domain of the EUROTRANS project, with the European Commission Integrated Infrastructure Initiative VELLA (Virtual European Lead LAboratory), and with the European Commission Specific Targeted Research Project ELSY (European Lead-cooled System) are also addressed.

  • Lecture (Conference)
    IV International Workshop on Materials for HLM cooled Reactors and Related Technologies, 21.-23.05.2007, Rom, Italy
  • Journal of Nuclear Materials 376(2008), 401-404

Permalink: https://www.hzdr.de/publications/Publ-9786
Publ.-Id: 9786


Magnetic resonance imaging of bone metastases in patients with nonseminomatous germ cell tumors

Froehner, M.; Aikele, P.; Beuthien-Baumann, B.; Kittner, T.; Oehlschlaeger, S.; Wirth, M. P.

Objective:

To investigate the role of magnetic resonance imaging (MRI) of bone metastases in nonseminomatous germ cell tumors.

Methods and Materials:

There were 5 consecutive patients with bone metastases from nonseminomatous germ cell tumors treated
between 2003 and 2006 who underwent imaging studies, including MRI. The characteristic imaging findings are discussed in the light of the clinical course.

Results:

Of the 5 patients, 3 had symptoms related to bone involvement at diagnosis. All patients received conventional x-ray of their bony lesions, but only 1 of them was considered abnormal. Skeletal MRI was obtained in all patients. A bone scan was available in 3 cases with spinal involvement. It was normal in 1 case and detected only a minority of the lesions visible on MRI in the other 2 cases. Follow-up MRIs were available in all patients. A partial resolution of bone involvement during chemotherapy was observed in only 1 of them. In 2 cases, there was a slight progression of a diffuse alteration of the bone marrow during treatment. In 1 patient, severe spinal bone marrow
changes were visible on MRI 2 years after cessation of treatment without evidence of disease recurrence.

Conclusions:

MRI may disclose bone metastases in nonseminomatous germ cell tumors, which otherwise may be missed. MRI findings of bone lesions during treatment do not directly reflect the course of the disease and have to be interpreted with caution using clinical information.

Keywords: Magnetic resonance imaging; Germ cell tumor; Bone metastases; Bone scan; Residual masses

Permalink: https://www.hzdr.de/publications/Publ-9785
Publ.-Id: 9785


Relative biological effectiveness of 25 kV and 10 kV X-rays for the induction of chromosomal aberrations in two human mammary epithelial cell lines

Beyreuther, E.; Dörr, W.; Lehnert, A.; Lessmann, E.; Pawelke, J.

Administration of ionizing radiation for diagnostic purposes can be associated with a risk for the induction of tumors. Therefore, particularly with regard to general screening programs, e.g. with mammography, cost-benefit considerations must be discussed including risk estimation depending upon the radiation quality administered. The present study was initiated to investigate the in vitro X-ray energy dependence for the induction of chromosomal aberrations in the two mammary epithelial cell lines, 184A1 and MCF-12A. The induced excess fragments, dicentric chromosomes and centric rings were analyzed and the relative biological effectiveness (RBE) was determined for 10 and 25 kV X-rays relative to 200 kV X-rays. The assumed energy dependence with higher values for 10 kV X-rays was confirmed for the excess fragments, with RBEM values of 1.92 +/- A 0.26 and 1.40 +/- A 0.12 for 10 kV X-rays and 1.17 +/- A 0.12 and 0.97 +/- A 0.10 for 25 kV photons determined for cell lines 184A1!
and MCF-12A, respectively. Meaningful results for the induction of dicentric chromosomes and centric rings were obtained only for higher doses with RBE values of 1.31 +/- A 0.21 and 1.70 +/- A 0.29 for 184A1 and 1.08 +/- A 0.08 and 1.43 +/- A 0.12 for MCF-12A irradiated with 25 and 10 kV X-rays, respectively.

Permalink: https://www.hzdr.de/publications/Publ-9784
Publ.-Id: 9784


Dynamische Benetzungsvorgänge an Katalysatorpartikeln: Modellierung und Experiment

Schubert, M.; Bott, S.; Lange, R.

Die Anwendung dynamischer Betriebsweisen bei abwärts durchströmten Festbettreaktoren zur Erhöhung der Phaseninteraktion und zur Steigerung der Katalysatoreffektivität wurde experimentell bereits erfolgreich nachgewiesen. Aufgrund der komplexen Zusammenhänge erfordern Modellierung und Simulation dynamisch betriebener Festbettreaktoren ein umfangreiches Wissen über makroskopische und mikroskopische Vorgänge und deren Kopplung. Bisherige Reaktormodelle vernachlässigen die Vorgänge im Katalysatorpartikel nahezu komplett oder verzichten auf die Kopplung mit Reaktormodellen.
Das entwickelte mehrskalige isotherme Modell setzt sich aus dem axialen Dispersionsmodell im Reaktormaßstab und einem Partikelmodell zur Berücksichtigung von dynamischen intrapartikulären Konzentrationsprofilen und Akkumulationen zusammen. Zusätzlich zur veränderlichen Teilbenetzung der Katalysatoroberfläche wird ein Verteilungsfaktor eingeführt, der die Morphologie der Flüssigkeit auf der Katalysatoroberfläche als Maß für die Gleichmäßigkeit der Verteilung beschreibt.
Das quasi-3D-Modell wurde in COMSOL MultiphysicsTM 3.2 umgesetzt und ermöglicht die Simulation ausgewählter dynamischer Zustände, die Ableitung günstiger Betriebsparameter zur Leistungssteigerung bei Festbettreaktoren und die Analyse optimaler Katalysatorkonfigurationen ohne aufwendige experimentelle Parameterstudien. Die Simulationsergebnisse für die Hydrierung eines organischen Lösungsmittels werden mit experimentellen Daten verglichen.

  • Poster
    ProcessNet-Jahrestagung 2007, 16.-18.10.2007, Aachen, Germany
  • Abstract in refereed journal
    Chemie Ingenieur Technik 79(2007)9, 1477-1478
    DOI: 10.1002/cite.200750266

Permalink: https://www.hzdr.de/publications/Publ-9783
Publ.-Id: 9783


Online-Monitoring als Methode zur Erhöhung der Sicherheit von Grignard-Reaktionen

Kryk, H.; Hessel, G.; Schmitt, W.

Metallorganische Verbindungen, wie beispielsweise Grignard-Reagenzien, haben große Bedeutung als Zwischenprodukte für organische Synthesen in der Feinchemie und der pharmazeutischen Industrie. Auf Grund des spezifischen Prozessverhaltens der stark exothermen Bildungsreaktionen und der hohen Reaktivität der Grignard-Reagenzien besitzen Grignard-Reaktionen ein hohes Gefahrenpotential. Von großer Bedeutung für die Prozesssicherheit ist deshalb die Entwicklung industriell anwendbarer Methoden für eine objektive Detektion des Reaktionsstarts und für die Online-Verfolgung von Edukt-Akkumulationen im Reaktionsgemisch des Rührkessel-Reaktors. Hierfür wurde eine wärmebilanzbasierte Online-Überwachungsmethode entwickelt und anhand von Experimenten im Miniplant getestet. Neben der Ermittlung von Konzentrationsverläufen ist mit der Methode eine Abschätzung von sicherheitsrelevanten Parametern realisierbar (on-line worst case calculations). Die Ergebnisse ermöglichen den Einsatz sicherheitsorientierter Regelungsstrategien für Grignard-Reaktionen. Gleichzeitig können derartige Systeme zu einer Erhöhung der Effizienz durch Steigerung der Raum-Zeit-Ausbeute sowie zur Realisierung einer inhärenten Prozesssicherheit beitragen. Durch Einbindung in ein komplexes Batch Information Management System (BIMS) können die Ergebnisse des Monitoring Systems chargenweise zusammen mit den Prozess-, Anlagen- und Analysedaten gespeichert und archiviert werden und dienen somit einer späteren Prozessanalyse und –optimierung.

  • Poster
    ProcessNet-Jahrestagung 2007, 16.-18.10.2007, Aachen, Germany
  • Abstract in refereed journal
    Chemie Ingenieur Technik 79(2007)9, 1441
    DOI: 10.1002/cite.200750027

Permalink: https://www.hzdr.de/publications/Publ-9782
Publ.-Id: 9782


Uran - Bindungsformen und Toxizität

Geipel, G.

  • Invited lecture (Conferences)
    ISS Kolloquium, 08.05.2007, Neuherberg, Deutschland

Permalink: https://www.hzdr.de/publications/Publ-9781
Publ.-Id: 9781


Bonding structure of fullerene-like carbon nitride thin films

Gago, R.; Jiménez, I.; Vinnichenko, M.; Neidhardt, J.; Hultman, L.; Möller, W.

There is no abstract provided.

Keywords: fulleren-like carbon nitride

  • Invited lecture (Conferences)
    9th International conference on Plasma Surface Engineering (PSE2004), 13.-17.09.2004, Garmisch-Partenkirchen, Germany

Permalink: https://www.hzdr.de/publications/Publ-9780
Publ.-Id: 9780


Growth of Carbon Nitride Thin Films by Low-energy Ion Beam Assisted Evaporation: on the Production of Fullerene-like Microstructure

Gago, R.; Vinnichenko, M.; Kreissig, U.; Czigany, Z.; Kolitsch, A.; Moeller, W.

Low-energy (<100eV) ion bombardment has been shown to be a key parameter in the production of hard and elastic carbon nitride (CNx) thin films with fullerene-like (FL) structure [1]. The production of FL-CNx is mostly reported for reactive magnetron sputtering but still the growth mechanisms are not clear [2]. In this way, the growth by ion beam assisted deposition (IBAD) would provide a better understanding since the source of neutrals and ions are independent. In this work we study the growth of CNx films produced by e-beam evaporation of graphite and simultaneous low-energy N2 ion assistance at different substrate temperatures. The low-energy ions were provided by an End-Hall ion source. The samples were characterized by spectroscopic ellipsometry, elastic recoil detection analysis (ERDA), Raman and high resolution transmission electron microscopy (HRTEM). Despite the low-energy ions, a high thermal-activated re-sputtering of the deposited films has been observed, indicating its chemical origin. In addition, the maximum nitrogen content in the films is limited to ~25 at.%, which should be related to the re-sputtering process. The Raman spectra and the optical properties indicate the dominance of sp2 hybrids. However, the results differ from those of FL-CNx, indicating that the sp2 hybrids are not arranged in a FL microstructure. This is also corroborated by HRTEM, where the samples were found to be mainly amorphous. Therefore, our results suggest that low-energy ion bombardment is not the main driving force for the promotion of FL arrangements, although this condition may be necessary to avoid damage on the growing microstructure. In this sense, the incorporation of neutrals, such as CxNy species formed during magnetron sputtering, may play a dominant role for the growth of FL-CNx [3].
1. Sjöstrom et al. Phys. Rev. Lett. 75 (1995) 1336. 2. Hultman et al. MRS Bulletin 28/3 (2003) 194. 3. Neidhardt et al. J. Appl. Phys. (in press).

Keywords: carbon nitride; fullerene-like structure; ion beam assisted deposition; Raman spectroscopy

  • Lecture (Conference)
    International Conference on Metallurgical Coatings and Thin Films, 19.04.2004, San Diego, USA

Permalink: https://www.hzdr.de/publications/Publ-9779
Publ.-Id: 9779


Real-time evolution of indium tin oxide properties during annealing in vacuum studied by in situ spectroscopic ellipsometry

Vinnichenko, M.; Rogozin, A.; Shevchenko, N.; Kolitsch, A.; Möller, W.

Thermal treatment of indium tin oxide (ITO) is often used as a method to decrease its resistivity. The amorphous-to-crystalline transition is often assumed as the reason for this improvement due to a Sn donor activation at elevated temperatures (Frank-Koestlin model), but the physical mechanisms behind the experimental observation are not clear. In present work, ITO thin films produced by reactive middle frequency magnetron sputtering were annealed in vacuum in two ways: 1) annealing within the temperature range Ta=20-330 °C at a constant heating rate of 5 °C/min, 2) isothermal annealing at Ta=210 and 240 °C. The amorphous layers and films with a small crystalline fraction have been investigated. This study is focused on in situ spectroscopic ellipsometry (SE) monitoring of the film properties during annealing. The SE data were reduced by using the Drude-Lorentz parameterization of ITO optical constants. In separate experiments, the films were investigated by in situ four point probe resistivity measurement technique and the in situ X-ray diffraction (XRD) in Bragg-Brentano geometry.
The observed temperature dependences of the ellipsometry parameters and resistivity indicate several stages (typically four) in contrast to the simpler two-stage behavior of these characteristics obtained during isothermal annealing. Even in the XRD-amorphous state, the film resistivity significantly decreases with increasing temperature due to a free-electron density enhancement as shown by SE. The increase of the free-electron density in this case can be attributed to the creation of oxygen vacancies due to relaxation of distorted In-O bonds in the amorphous phase. Since Sn is known not to be electrically active in amorphous ITO and does not affect the free-electron density, any creation of substitutional Sn in the amorphous film can be neglected. Tin donor activation gives significant contribution to a free electron density only at temperatures above 250 °C which agrees with the crystallization onset suggested by in situ XRD. The crystallization kinetics is analyzed by using the Kolmogorov–Johnson–Mehl-Avrami equation which yielded a kinetic exponent of the process of approximately 3. Under the condition that the coherently diffracting domain size is smaller than the film thickness, this kinetic exponent indicates a three-dimensional crystallization process. The refractive index decreases at increasing annealing temperature above 150 °C. An even stronger decrease is observed above Ta=250 °C, both processes are related to the enhancement of the free electron density.

Keywords: ITO optical properties; in siut ellipsometry; annealing

  • Lecture (Conference)
    5th International Young Scientists Conference, Problems of Optics and High Technology Material Science, SPO 2004, 27.-31.10.2004, Kyiv, Ukraine

Permalink: https://www.hzdr.de/publications/Publ-9778
Publ.-Id: 9778


Silicon based photonics

Dekorsy, T.

  • Lecture (others)
    Philips Research, 04.06.2004, Eindhofen, NL

Permalink: https://www.hzdr.de/publications/Publ-9777
Publ.-Id: 9777


Silicon based photonics

Dekorsy, T.

  • Lecture (others)
    AMOLF, 29.03.2004, Amsterdam, NL

Permalink: https://www.hzdr.de/publications/Publ-9776
Publ.-Id: 9776


Technical development at the Materials Research end-station

Oehme, W.; Dienel, S.; Strauch, U.; Eichhorn, F.; Schell, N.

The report summarizes the most important technical developments realized in 2003/2004 at the Materials Research end-station. There are described new programs which simplify the visualisation and analysis of a large amount of data. These data are collected by a linear position sensitive detector (PSD) and a multi-channel analyzer. Additionally, an electronic stepperrmotor controller switch had been developed. It allows to use two different types of stepper motor controllers to control four of the axes of a 6-circle HUBER-diffractometrer by two different instrumentation systems.

  • Contribution to HZDR-Annual report
    Wissenschaftlich-Technische Berichte / Helmholtz-Zentrum Dresden-Rossendorf; FZR-418 März 2005, 47-49
    ISSN: 1437-322X

Downloads

Permalink: https://www.hzdr.de/publications/Publ-9775
Publ.-Id: 9775


Ein Schwermetall sieht (infra-)rot

Foerstendorf, H.

Tag des offenen Labors, FZD

  • Lecture (others)
    Tag des offenen Labors, 12.05.2007, FZD, Deutschland

Permalink: https://www.hzdr.de/publications/Publ-9774
Publ.-Id: 9774


Improving the detection limit of the Radiochemistry end-station

Oehme, W.; Dienel, S.; Claußner, J.; Strauch, U.; Hennig, C.; Scheinost, A. C.

A new multi-element detector with higher energy resolution was aqcuired which is instrumented with a high-rate digital multi-analysis spectrometer from X-ray Instrumentation Associates (XIA) which is particularly well suited for EXAFS with multi-element detectors. The installation of this new detector involved not only electronic instrumentation and software development, but - due to the complex radiochemical safety system at the Radochemistry end-station -also mechanical engineering.

  • Contribution to HZDR-Annual report
    Wissenschaftlich-Technische Berichte / Helmholtz-Zentrum Dresden-Rossendorf; FZR-418 März 2005, 44-46
    ISSN: 1437-322X

Downloads

Permalink: https://www.hzdr.de/publications/Publ-9773
Publ.-Id: 9773


Can direct field-evaporation of doubly-charged ions and post-ionisation from singly-charged state co-exist ?

Ganetsos, T.; Mair, A. W. R.; Bischoff, L.; Akhmadaliev, C.; Aidinis, C. J.

A tin liquid metal ion source (LMIS) containing ~ 13% Pb has been studied. From a careful examination of the mass spectra of the source it is concluded that post-ionisation is a most probable mechanism for the formation of Pb++ ions. In the case of tin, however both Sn+ and Sn++ appear to form by direct field-evaporation. This view is supported by energy deficit measurements on the Sn+ and Sn++ beams . Our results for Pb++/Pb+ agree with those of Komuro (1983) with a pure Pb source. The reason for this is understandable and is related to the similarity between the evaporation fields of Sn and Pb. For the sake of completeness we also present measurements of the energy spread of the Sn++ and Sn+ beams.

Keywords: tin liquid metal ion source; liquid metal cone; mass spectra; field-evaporation; post-ionisation

  • Lecture (Conference)
    49th International Field Emission Symposium (IFES 04), 12.-15.07.2004, Seggau castle, Graz, Austra
  • Surface and Interface Analysis 39(2007)2-3, 128-131

Permalink: https://www.hzdr.de/publications/Publ-9772
Publ.-Id: 9772


Coherent phonons in condensed matter

Dekorsy, T.

  • Lecture (others)
    Kolloquium of SFB 450, 18.05.2004, Berlin, D

Permalink: https://www.hzdr.de/publications/Publ-9771
Publ.-Id: 9771


The temperature dependence of energy spread and mass spectra of an Au73Ge27 alloy liquid metal ion source

Pilz, W.; Bischoff, L.; Akhmadaliev, G. L. R.; Mair, C.; Aidinis, C. J.; Ganetsos, T.

Focused ion beam applications using ions other than Gallium are of increasing interest during the previous years. A promising candidate is Germanium due to its compatibility to the semiconductor technology, i.e. for local doping of SixGe1-x structures. The energy spread ΔE½ of the source, which, through the chromatic aberrations of the system, determines the final spot size at the target and the peak energy deficit (PED) as well as the mass spectra emitted from an eutectic Au73Ge27 (m.p.=366°C) alloy liquid metal ion source were investigated as a function of the emitter temperature. ΔE½, measured with a retarding field analyser, is expressed as the full width of the distribution at half its maximum height (FWHM). Doubly-charged ions achieve double of energy, compared to singly-charged ions, which is taken into account for analysis. Furthermore, Ge shows a much more abundant in the doubly-charged state, following Brandon`s criterion. Due to the analysis of PED we think Ge++ as well as Au+ and Ge+ are directly field-evaporated in the doubly- and singly-charged state, respectively. Au++ should be post-ionized from the singly-charged state.
Due to the regular expected behaviour of the surface tension dependence on temperature shows in contrast to Si containing metallic glass alloys, like AuSi or AuGeSi, that the ion emission is enhanced with increasing temperature, obtained from a field of I-V-characteristics. The slope of this change also depends on the volume of the source reservoir, which is demonstrated for a drop volume of 0.5 and 3.4 mm3, respectively, in the temperature range from 400 to 1000 °C. The mass spectra, measured with an E x B analyser are evaluated with respect to the emission intensity for the main ion species Au+ and Au++, Ge+ and Ge++ and for various molecular ions and clusters, formed by droplet disintegration. The ratio of doubly-charged to singly-charged monomer species is given as a function of temperature in the emission current range of 1 to 30 µA.

Keywords: alloy liquid metal ion source; FIB; AuGe

Related publications

  • Lecture (Conference)
    49th International Field Emission Symposium (IFES 04), 12.-15.07.2004, Seggau Castle, Graz, Austria

Permalink: https://www.hzdr.de/publications/Publ-9770
Publ.-Id: 9770


nm scale resolution single ion implantation into diamond for quantum dot production

Burchard, B.; Meijer, J.; Rangelow, I.; Bischoff, L.

NV-centres are commonly known as good candidates for spintronic and optical quantum computer applications. These centres have already been used to construct single photon sources .
We present a set up to position / implant single atoms with nm resolution into diamond surface. An atomic force microscope (AFM) tip and a focused ion beam (FIB) set up form the core of our set up. High precision positioning of atoms requires cooled atom handling. An accuracy of more than 5nm requires ion energies below 1keV. Otherwise single ion impact detection becomes impossible at these low energies. We discuss these requirements and challenges and present a suitable solution based on an AFM tip acting as a collimator diaphragm.

Keywords: Diamond; NV centers; AFM tip; FIB

  • Lecture (Conference)
    15th European Conference on Diamond, Diamond-Like Materials, Carbon Nanotubes, Nitrides & Silicon Carbide , DIAMOND 2004, 12.-17.09,2004, Riva del Garda, Italy

Permalink: https://www.hzdr.de/publications/Publ-9769
Publ.-Id: 9769


Technical developments at ROBL

Oehme, W.; Pröhl, D.; Dienel, S.; Claußner, J.; Strauch, U.; Funke, H.; Scheinost, A. C.

The article describes the most important technical improvments which had been performed at the beamline ROBL in 2005 and 2006. These are new systems such a cryostat and a sample holder which unifies the adjustment of samples in the glove box. Additionally, there was an update of electronics and basic software to enhance the compatibility with the standard equipment used at ESRF beamlines (migration from OS9 to Linux operating systems, new instrumentation of beamposition monitors.) There was also a SMS-based warning system installed to inform the responsible beamline scientist in case of problems during unattended experiments.

  • Contribution to HZDR-Annual report
    Wissenschaftlich-Technische Berichte / Helmholtz-Zentrum Dresden-Rossendorf; FZD-463 März 2007, 43-46
    ISSN: 1437-322X

Permalink: https://www.hzdr.de/publications/Publ-9768
Publ.-Id: 9768


Concept of an ion implantation stage with atomistic resolution

Rangelow, I. W.; Ivanova, K.; Ivanov, T.; Meijer, J.; Burchard, B.; Park, S. J.; Persaud, A.; Schenkel, T.; Bischoff, L.

We propose a method for deterministic implantation of single atoms into solids which relies on a linear ion trap as an ion source. Our approach allows a deterministic control of the number of implanted atoms and a spatial resolution of less than 1 nm. Furthermore, the method is expected to work for almost all chemical elements. The deterministic implantation of single phosphor or nitrogen atoms is interesting for the realization of scalable solid state quantum computers, in particular for silicon and diamond based schemes. A wide range of further applications is expected for the fabrication of nano-electric devices.

Keywords: single ion implantation; AFM tip; FIB; stage

  • Lecture (Conference)
    9th International Conference on Nuclear Microprobe Technology and Applications, ICNMTA04, 13.-17.09.2004, Dubrovnik, Croatia

Permalink: https://www.hzdr.de/publications/Publ-9767
Publ.-Id: 9767


Surface plasmon propagation in metallic nanostructures

Seidel, J.; Grafström, S.; Bischoff, L.; Eng, L.

The generation of surface plasmon polaritons (SPPs) at isolated nanoholes in 100 nm thick Au films is studied using near-field scanning optical microscopy. Finite-difference time-domain calculations,some explicitly including a model of the scanning tip, are used to interpret the results. We find the holes act as point-like sources of SPPs and demonstrate that the interference between the SPP and a directly transmitted wave allows determination of the wavelength, phase, and decay length of the SPP. The near-field intensity patterns can be manipulated by varying the angle and polarization of the incident beam.

Keywords: surface plasmon polaritons; focused ion beam; nanostructures

  • Lecture (Conference)
    Int. Workshop and Seminar on Cooperative Phenomena in Optics and Transport in Nanostructures, 10.-20.06.2004, Dresden, Germany

Permalink: https://www.hzdr.de/publications/Publ-9765
Publ.-Id: 9765


Hard- und Software des Radiochemiemessplatzes ROBL an der ESRF/Grenoble

Oehme, W.; Scheinost, A. C.; Hennig, C.; Funke, H.; Roßberg, A.; Reich, T.; Claußner, J.; Dienel, S.

Der Messplatz des Instituts für Radiochemie am Synchrotron der ESRF in Grenoble/Frankreich wird aus der Sicht der elektronischen Instrumentierung beschrieben. Der Schwerpunkt liegt auf dem benutzten Messprinzip und der gewählten Hard- und insbesondere Softwarestruktur. Insbesonder wird auf das benutzte Messprogramm "xatros", das eine messplatzspezifische ROBL-Eigenentwicklung ist, eingegangen.

  • Contribution to external collection
    Dr.F.Wulf: Bericht Frühjahrstagung Studiengruppe Elektronische Instrumentierung 27.-29-März 2006, Berlin: Hahn-Meitner-Institut Berlin, 2006, 0936-0891, 197-212

Permalink: https://www.hzdr.de/publications/Publ-9764
Publ.-Id: 9764


Vibrational spectroscopic and DFT studies of the metal-nitride clusterfullerenes: cluster-cage interactions and molecular structures

Popov, A. A.; Dunsch, L.; Krause, M.; Yang, S.; Kalbac, M.

Significant progress in the synthesis and isolation of trimetallic-nitride (TNT) clusterfullerenes has been achieved in the recent years, with a variety of M3N (M=Sc, Y, Gd-Lu) being encapsulated in various C2n (n=34-44) cages (see Ref.[1] for review and references therein). However, structural information for many of the new structures remains limited because of the low available amounts, which often appear insufficient for X-ray crystallographic or 13C NMR spectroscopic studies. IR and Raman spectroscopy, which require substantially smaller amounts of the material, have been extensively used in our group for characterization of new clusterfullerenes.[2] In this work we develop the general methodology allowing elucidation of molecular structures of new clusterfullerenes based on the vibrational spectroscopy and DFT computations.

Keywords: fullerenes; cluster compounds; vibrational spectroscopy

  • Lecture (Conference)
    211th ECS Meeting, 06.-10.05.2007, Chicago, USA

Permalink: https://www.hzdr.de/publications/Publ-9763
Publ.-Id: 9763


Study on the formation of open-eye and slag entrainment in a gas stirred ladle

Thunman, M.; Eckert, S.; Hennig, O.; Björkvall, J.; Du, S.

Laboratory experiments were carried out to study the phenomena related to open-eye formation in ladle treatment. Ga-In-Sn alloy with a melting temperature of 283 K was used to simulate the liquid steel, while MgCl2-Glycerol(87%) solution as well as HCl solution were used to simulate the ladle slag. No open-eye was formed at lower gas flow rates, but, occurred when gas flow reached a critical rate. This critical gas flow rate was found to depend significantly on the height of the top liquid. No noticeable amount of top liquid was observed in any of the samples taken from the metal bulk during gas stirring. To confirm this aspect, samples of slag-metal interface were taken around the open-eye in an industrial gas stirred steel ladle. No entrapped slag droplet was found in the solidified steel within the region between the interface and 2 cm from the interface. The accordance of the laboratory and industrial results suggests that the entrainment of slag into the steel bulk around the open-eye cannot be considered as the major contribution to inclusion formation.

Keywords: cold model; inclusion; slag entrapment; Ga-In-Sn alloy; open-eye; steel-slag interface

  • Steel Research International 78(2007)12, 847-854

Permalink: https://www.hzdr.de/publications/Publ-9762
Publ.-Id: 9762


Proton-recoil detectors for time-of-flight measurements of neutrons with kinetic energies from some tens of keV to a few MeV

Beyer, R.; Grosse, E.; Heidel, K.; Hutsch, J.; Junghans, A. R.; Klug, J.; Legrady, D.; Nolte, R.; Röttger, S.; Sobiella, M.; Wagner, A.

For experiments at the superconducting electron accelerator ELBE, where neutrons in the kinetic energy region from some tens of keV to a few MeV will be produced by bremsstrahlung, neutron-time-of-flight detectors have been developed. These detectors are made from the plastic scintillator material EJ-200. Efficiency calibration showed more than 10% efficiency for kinetic energies down to 30 keV. The calibration was done at the “accelerator facility for fast neutron research” at Physikalisch-Technische Bundesanstalt in Braunschweig, using pulsed quasi-monoenergetic neutron fields with a well-determined fluence. The low detection threshold was obtained by coincident readout of two Hamamatsu R2059-01 photomultiplier tubes per scintillator and by triggering just below the single-photo-electron peak of these photomultiplier tubes, which additionally gives a well-reproduceable detection threshold.

Keywords: neutron detector proton-recoil detector; fast neutrons; neutron time of flight; nELBE

  • Nuclear Instruments and Methods in Physics Research A 575(2007), 449-455
    DOI: 10.1016/j.nima.2007.02.096
    Cited 32 times in Scopus
  • Poster
    2008 Nuclear Science Symposium, 12.-25.10.2008, Dresden, Deutschland
  • Contribution to proceedings
    2008 IEEE Nuclear Science Symposium, 19.-25.10.2008, Dresden, Deutschland
    Nuclear Science Symposium Conference Record, 2008. NSS '08.
    DOI: 10.1109/NSSMIC.2008.4774625

Permalink: https://www.hzdr.de/publications/Publ-9761
Publ.-Id: 9761


CW Operation of the TTF-III Input Coupler

Knobloch, J.; Martin, M.; Anders, W.; Bauer, S.; Pekeler, M.; Belomestnykh, S.; Kostin, D.; Möller, W.; Büchner, A.; Büttig, H.; Gabriel, F.

Several newly proposed superconducting linacs are designed to use TESLA technology operating CW rather than pulsed for which the system was developed. It must therefore be demonstrated that CW operation is feasible. Here we describe a series of CW tests with the TTF-III power coupler to determine the average power limit. These tests were performed on a coupler test stand both at room temperature at the FZ Rossendorf and under cryogenic operating conditions in BESSY’s HOBICAT[1] facility. An extrapolation of the measurements suggests that the coupler can handle 5 kW CW standing wave. It was also demonstrated that even higher power levels are feasible if the cooling of the inner conductor is modified.

  • Contribution to proceedings
    PAC Particle Accelerator Conference 2005, 16.-20.05.2005, Knoxville, TN, USA
    Proceedings of 2005 Particle Accelerator Conference, 3292-3294

Permalink: https://www.hzdr.de/publications/Publ-9760
Publ.-Id: 9760


Radiochemische Synthesen von [F-18]-markierten bicyclischen Vesamicol-Derivaten als potentielle Radioliganden für den vesikulären Acetylcholin-Transporter (VAChT)

Fischer, S.; Vercouillie, J.; Scheunemann, M.; Hiller, A.; Sorger, D.; Sabri, O.; Steinbach, J.

Ziel/Aim:

Für den Transport von Acetylcholin in die präsynaptischen Vesikel im Hirn ist der vesikuläre Acetylcholintransporter (VAChT) verantwortlich. Zur Diagnose cholinerger Läsionen im Gehirn und deren Visualisierung mit Hilfe von PET sind insbesondere F-18-Radioliganden von großem Interesse, die spezifisch an den VAChT binden. Solche Tracer leiten sich von der Struktur des Vesamicols ab. Auf Basis von Untersuchungen zur Strukturoptimierung potentiell neuer Radiotracer werden Radiosynthesen ausgewählter bicyclischer Vesamicol-Derivate vorgestellt.

Methodik/Methods:

Zur Verbesserung der pharmakologischen Eigenschaften gegenüber Benzyloxyvesamicol-Derivaten wurden Verbindungen des 6-(4-Phenyl-piperidin-1-yl)-octahydro-benzo[1,4]oxazin-7-ols abgeleitet. Im Ergebnis von detaillierten Bindungsstudien wurden als Derivate [F-18]F-acetyl- ([F-18]VL115), 4-[F-18]F-benzoyl- ([F-18]VL112), 4-[F-18]F-benzyl- ([F-18]VL64) und [F-18]F-propyl für erste Radiosynthesen ausgewählt, wobei für [F-18]VL115 ein Br-, für [F-18]VL112 ein Nitro-Präkursor verfügbar war und für [F-18]VL64 eine Aufbausynthese mit 4-[F-18]Fluorbenzylbromid (FBBr) angestrebt wurde.

Ergebnisse/Results:

Die Synthese von [F-18]VL115 erfolgt durch nukleophile Radiofluorierung des Präkursors in DMF (145-155°C, 15 min) und nachfolgende Abtrennung des Zielproduktes durch SPE und anschließende HPLC. Das Endprodukt wurde mittels TLC, Radio-HPLC und GC charakterisiert: Radiochemische Reinheit 99,0 %, spezifische Aktivität: 34-100 GBq/#mikro#mol. Die Synthese konnte auf einen Automaten (TRACERlab, Fa. GE/Healthcare) übertragen werden (Synthesezeit ca. 1,6 h, Ausbeute 23 %). Zentraler Schritt der Synthese von [F-18]VL112 ist die nukleophile Substitution der Nitrogruppe durch nicht konventionelles Erhitzen mit Mikrowellen in DMF (150 Watt, 150-156°C, 15 min). Das Produktgemisch enthält noch Reste an nicht-abtrennbarem Präkursor. Die Separation gelingt nach Reduktion mit Pd/Ammoniumformiat in MeOH. Nach Feinreinigung mit SPE und HPLC ist der Radiotracer in hoher Reinheit und spez. Aktivität erhältlich (98,5 % bzw. 35-150 GBq/#mikro#mol), jedoch nur in moderater Ausbeute (≤15 %). Als Voraussetzung für die Darstellung von [F-18]VL64 wurde [F-18]FBBr in ausreichender Menge in einem verbesserten Verfahren erhalten. In ersten Versuchen wurden signifikante Unterschiede im Reaktionsverhalten zwischen nicht-radioaktiven Reaktionspartnern zum Umsatz mit [F-18]FBBr bei analoger Reaktionsführung festgestellt.

Schlussfolgerungen/Conclusions:

Die vorgestellten Radiosynthesen ermöglichen eine sichere reproduzierbare Herstellung der Radiotracer [F-18]VL115, [F-18]VL112 und deren Formulierung als sterile ethanolische Lösung. Zur Herstellung von [F-18]VL115 wurde eine automatisierte Synthese unter Nutzung eines kommerziellen Synthesemoduls entwickelt.

  • Lecture (Conference)
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A43
    ISSN: 0029-5566

Permalink: https://www.hzdr.de/publications/Publ-9759
Publ.-Id: 9759


Helical magnetorotational instability in a liquid metal Taylor-Couette experiment

Gundrum, T.; Gerbeth, G.; Stefani, F.; Rüdiger, G.; Szklarski, J.; Hollerbach, R.

Cosmic magnetic fields are not only passive by-products of the hydromagnetic dynamo effect, they also play an active role in the formation of stars and black holes by virtue of the Magnetorotational Instability (MRI). By destabilizing Keplerian flows which are hydrodynamically stable due to Rayleighs criterion, the MRI enables outward transport of angular momentum in accretion discs. The effort to investigate the MRI in a liquid metal experiment can be dramatically reduced if the purely axial magnetic field is replaced by a helical magnetic field. We present results of a Taylor-Couette experiment with the liquid metallic alloy GaInSn under the influence of helical magnetic fields that show typical features of MRI at Reynolds numbers of the order 1000 and Hartmann numbers of the order 10.

  • Lecture (Conference)
    15th International Couette-Taylor Workshop, 09.-12.07.2007, Le Havres, France
  • Contribution to proceedings
    15th International Couette-Taylor Workshop, 09.-12.07.2007, Le Havre, France
    Proceedings of the 15th International Couette-Taylor Workshop, Le Havre, 266-269

Permalink: https://www.hzdr.de/publications/Publ-9758
Publ.-Id: 9758


Ionen in der Materialforschung und verdünnte magnetische Halbleiter

Talut, G.

Grundlagen der Ionenstrahlphysik und der verdünnten magnetischen Halbleiter

  • Lecture (others)
    Vortrag im Rahmen der Vorlesung zur Oberflächentechnik, 04.05.2007, Wildau, Deutschland

Permalink: https://www.hzdr.de/publications/Publ-9757
Publ.-Id: 9757


TiSi2-Nanostructures - Enhanced Conductivity at Nanoscale?

Enyashin, A. N.; Gemming, S.

The stability, the structural and the electronic properties of elongated titanium silicide nanostructures have been investigated by density-functional-based tight-binding calculations. Our results show that the strain energy in tubular form does not follow the trends observed for other layered materials; tubes from TiSi2 are more stable than the flat monolayer, because in nanotubes free valences of Ti and Si atoms can be saturated for geometric reasons. Multi-layered tubes are energetically favoured and exhibit a tendency towards facetting. All such nanostructures are metallic with a density of Ti(3d) states at the Fermi level, which is considerably higher than that of the bulk compound. Thus, nanostructured TiSi2 may exhibit a better conductivity than the bulk phase along the tube direction.

Keywords: inorganic nanotube; silicide; nanowire; electronic structure

Permalink: https://www.hzdr.de/publications/Publ-9756
Publ.-Id: 9756


Oxidized and glycated LDL isolated from subjects with impaired glucose tolerance increases CD36 and PPARgamma gene expression in macrophages

Graessler, J.; Pietzsch, J.; Westendorf, T.; Julius, U.; Bornstein, S. R.; Kopprasch, S.

kein Abstract verfügbar

  • Poster
    113. Internistenkongreß, 15.-18.04.2007, Wiesbaden, Deutschland
  • Abstract in refereed journal
    Medizinische Klinik 102(2007)4, S94

Permalink: https://www.hzdr.de/publications/Publ-9755
Publ.-Id: 9755


In vivo glycoxidation of low density lipoprotein from subjects with impaired glucose tolerance increases CD36 and PPARgamma gene expression in macrophages

Kopprasch, S.; Pietzsch, J.; Bornstein, S. R.; Graessler, J.

kein Abstract verfügbar

  • Lecture (Conference)
    51. Jahrestagung der Gesellschaft für Thrombose- und Hämostaseforschung, 21.-24.02.2007, Dresden, Deutschland
  • Open Access Logo Abstract in refereed journal
    Hämostaseologie 27(2007)1, A7

Permalink: https://www.hzdr.de/publications/Publ-9754
Publ.-Id: 9754


Influence of glucose challenge on 2-deoxy-2-[18F]fluoro-D-glucose small animal positron emission tomography (PET) studies in rats

Bergmann, R.; Bergmann, S.; Pietzsch, J.

Imaging of regional glucose metabolism in small animals by dynamic PET Imaging of regional glucose metabolism in small animals by dynamic PET studies using 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) provides the unique possibility to study normal physiology and pathophysiological situations in various disease models in vivo. However, plasma glucose levels and other factors influence 18F-FDG PET studies. Therefore, we examined and compared the tissue-specific 18F-FDG uptake and kinetics in rats without and with a glucose challenge. 18F-FDG kinetics was studied for one hour in anesthetized rats using a dedicated small animal PET system. The animals were injected intravenously with 18F-FDG without (control) or simultaneously with glucose (270 mg/kg body weight). PET images were reconstructed and three-dimensional regions of interest were determined for subsequent data analysis. The plasma glucose concentrations one hour after injection were similar in the control and post challenge group. Tissue-specific 18F-FDG uptake, e.g., in brain, heart and liver, tends to be lower in the post challenge group as compared to the controls. Only with increasing body weight (>250 g) post challenge plasma glucose increased. However, in the post challenge group the kinetics of 18F-FDG was different only in the first 15 min after injection when compared to the controls, but subsequently converged to control kinetics within the following 45 min. In summary, glucose challenge did not influence the tissue-specific distribution pattern of 18F-FDG due to the high glycolysis rate of the rat. On the other hand, in diabetic models, older or larger animals the effects of increased plasma glucose levels should be taken into account for interpretation of PET data.

  • Poster
    2nd International Congress on Prediabetes and the Metabolic Syndrome, 25.-28.04.2007, Barcelona, Spain
  • Abstract in refereed journal
    Diabetes and Vascular Disease Research 4(2007)Suppl. 1, S219

Permalink: https://www.hzdr.de/publications/Publ-9753
Publ.-Id: 9753


High resolution magnetic resonance imaging and spectroscopy of adipose tissue deposits in mice

Strobel, K.; van den Hoff, J.; Pietzsch, J.

Adipose tissue (AT) plays a crucial role in the pathogenesis of the metabolic syndrome. In this line, for investigation of AT biology and disorder rodent models gain increasing importance. However, non-invasive differentiation and characterization of AT deposits in rodents in vivo is a current challenge. In the present study, high resolution magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques were applied for quantitative in vivo evaluation of various brown adipose tissue (BAT) and white adipose tissue (WAT) deposits in mice. Experiments were carried out in NMRI and nude mice, respectively. Morphological differentiation between various AT deposits was obtained by 1H-MRI at 7 Tesla. Images were obtained with high spatial resolution of 156 microns. Furthermore, 1H-MRS has been performed to quantify in vivo different lipid patterns in BAT and WAT deposits using a volume selective PRESS sequence on 3 to 8 mm3 voxels. In both NMRI and nude mice various BAT and WAT deposits were clearly distinguished from the non-AT tissue with excellent contrast by T1-weighted MSME MRI sequences. High resolution spectra obtained at 7 Tesla allow identification of at least 9 different proton resonances specific for lipids, and, thus, for exact calculation of mono- to polyunsaturated fatty acid ratio in vivo. In this study, nude mice showed, e.g., a 4-fold higher degree of polyunsaturation of triglyceride fatty acids in BAT when compared to NMRI mice. High-resolution MRI and MRS are potentially useful tools for studying the biology of different BAT and WAT deposits non-invasively in rodent models in vivo.

  • Poster
    International Congress on Prediabetes and the Metabolic Syndrome, 25.-28.04.2007, Barcelona, Spain
  • Abstract in refereed journal
    Diabetes and Vascular Disease Research 4(2007)Suppl. 1, S195

Permalink: https://www.hzdr.de/publications/Publ-9752
Publ.-Id: 9752


Factors influencing the formation of small dense LDL particles

Julius, U. A.; Dittrich, M.; Pietzsch, J.

Aims:

We wanted to study factors influencing the size of LDL particles.

Material and methods:

752 persons (330 males, 422 females) have been studied. We performed an OGTT (plasma glucose, insulin, proinsulin). Triglycerides (TG), total cholesterol (TC) and protein (in whole plasma, in VLDL, in LDL) and HDL cholesterol have been measured. The size of the LDL particles has been estimated using a gel electrophoresis
(in LDL subclasses 1 – 3, mean LDL particle diameter, affiliation to phenotypes A or B). Probands have been subdivided into those with normal glucose tolerance (n 540), with an impaired glucose tolerance (n 137), with a newly discovered or known diabetes (n 51), or with a diabetes mellitus which was treated by insulin (n 24). The
Metabolic Syndrome (MS) has been defined according to the NCEP criteria.

Results:

In 29 % of all probands a MS was observed. These probands had a significantly smaller mean LDL particle diameter (25.5 nm) than those persons without a MS (26.2 nm). In univariate analysis (partially adjusted for fasting plasma glucose, proinsulin, insulin, gender, age, body mass index) the mean LDL diameter showed significant
correlations with the VLDL TG, plasma TG, VLDL cholesterol, VLDL proteins and HDL cholesterol. In a linear stepwise regression analysis in the different groups of glucose tolerance different independent factors of influence were seen. Conclusions: The data obtained show the significance of TG levels, of glucose intolerance and the presence of the MS for the formation of atherogenic small dense LDL particles.

  • Poster
    2nd International Congress on Prediabetes and the Metabolic Syndrome, 25.-28.04.2007, Barcelona, Spain
  • Abstract in refereed journal
    Diabetes and Vascular Disease Research 4(2007)Suppl. 1, S219

Permalink: https://www.hzdr.de/publications/Publ-9751
Publ.-Id: 9751


In vivo metabolism of glycated and glycoxidized LDL: insights from small animal positron emission tomography (PET) studies

Pietzsch, J.; Haase, C.; Hoppmann, S.; Bergmann, R.; Wüst, F.; van den Hoff, J.

Data concerning the role of circulating glycated (glycLDL) and glycoxidized LDL (glycoxLDL) in atherogenesis and other pathologies are scarce. One reason for this is the lack of suitable radiolabeling methods for direct assessment of metabolic pathways of modified LDL in vivo. We report a novel approach for specific labeling of human native LDL (nLDL), glycLDL, and glycoxLDL with the positron emitter fluorine-18 (18F) by either N-succinimidyl-4-[18F]fluorobenzoate or N-[6-(4-[18F]fluorobenzylidene)-aminooxyhexyl]maleimide (radiochemical yields, 15-40%; specific radioactivity, 150-400 GBq/µmol). Radiolabeling itself caused neither additional oxidative structural modifications of LDL constituents nor adverse alterations of their biological activity and functionality in vitro. The approach was evaluated with respect to binding and uptake of 18F-nLDL, 18F-glycLDL, and 18F-glycoxLDL in cells overexpressing various lipoprotein-recognizing receptors. The metabolic fate of 18F-labeled nLDL, glycLDL, and glycoxLDL in vivo was delineated by dynamic small animal PET studies in rats. Dynamic PET data demonstrated a significantly delayed catabolism of glycLDL when compared with nLDL. In contrast, glycoxLDL showed an enhanced catabolism when compared with nLDL. The in vivo distribution and kinetics of nLDL, glycLDL, and glycoxLDL correlated well with the anatomical localization and functional expression of LDL receptors, scavenger receptors, and receptors for advanced glycation end products. The study shows that LDL modification in part or fully blocks binding to the LDL receptor, and reroutes modified LDL to various tissue-specific pathways. In this line, 18F-labeling of LDL and the use of small animal PET provide a valuable tool for imaging and functional characterization of these pathways in animal models in vivo.

  • Poster
    2nd International Congress on Prediabetes and the Metabolic Syndrome, 25.-28.04.2007, Barcelona, Spain
  • Abstract in refereed journal
    Diabetes and Vascular Disease Research 4(2007)Suppl. 1, S220

Permalink: https://www.hzdr.de/publications/Publ-9750
Publ.-Id: 9750


Hydration and water exchange mechanism of the UO22+ ion revisited: The validity of the "n+1" model

Tsushima, S.

Hydration and water exchange mechanism of the UO22+ ion was studied by the B3LYP calculations. Relative Gibbs energies in aqueous phase of the 4-, 5-, and 6-fold uranyl(VI) hydrates were compared. A model with a complete first hydration shell and one water in the second shell was used (which is called "n+1" model) to compare the energy of the UO22+ ion with different hydration number. The "n+1" model tends to overestimate the overall stability of the complex, and this type of model should be carefully used for the determination of the coordination number or the coordination mode such as unidentate or bidentate. A stable 5-fold uranyl(VI) hydrate go through a very rapid water exchange process via an associative (A-) mechanism keeping the 5-fold uranyl(VI) being dominant species.

Permalink: https://www.hzdr.de/publications/Publ-9749
Publ.-Id: 9749


Tc-99m labelled fatty acids for myocardial metabolism imaging

Walther, M.; Pietzsch, H.-J.; Pietzsch, J.; Bergmann, R.; Wunderlich, G.; Mirtschink, P.; Deussen, A.

Ziel/Aim:

Radiolabelled fatty acids displaying efficient myocardial uptake and adequate retention are attractive candidates for the clinical evaluation of regional discrepancies in the cardiac metabolism and energy turnover (1). The aim of this work is the substitution of the accelerator produced radiolabel I-123 for FA against the low price generator radionuclide Tc-99m (2).

Methodik/Methods:

Synthesis and physico-chemical characterization of the new Tc-99m labelled FA derivatives were followed by in vitro and in vivo experiments for their biological evaluation. Experiments on isolated perfused rat hearts provide a simple and well reproducible approach to detect promising Tc-99m compounds for biodistribution experiments. Biodistribution and metabolism studies in male Wistar rats after a single intravenous injection of various Tc-99m-labelled FA were investigated (3).

Ergebnisse/Results:

A very rapid disappearance of Tc-99m tracer concentration from the blood circulation was observed for all compounds. C11S FA showed the highest uptake with 2.0% ID/g tissue (alternatively 3.6% by addition of Tween 80) in the rat heart. Liver and kidneys are mainly responsible for fast removal of Tc-99m derivatives from the circulation. At 5 min after injection, approximately 50% of the injected dose is liver-associated. A substantial fraction is cleared by the kidneys and approximately 6% of the injected dose is kidney-associated at 5 min p.i. Overall, fast systemic clearance of Tc-99m species after injection of Tc-99m labelled FA in the rat is explained by the rapid hepatobiliary and renal elimination of Tc-99m species. On the other hand, the low mean accumulation of Tc-99m compounds in the thyroid gland (<0.07 %ID at 5 min; <0.07 %ID at 60 min) and the stomach (<1.7 %ID at 5 min; < 3.9% at 60 min), respectively, which express the sodium-iodide transporter is indicative of a very low abundance of pertechnetate in vivo.

Schlussfolgerungen/Conclusions:

Experiments on isolated perfused rat hearts showed very high ventricular extraction rates of the FA complexes, being in the order C11 compound (26.6% ± 3.7, n= 12), C12 (24.4% ± 4.9, n= 5), and C11S (23.4% ± 4.9, n= 5). These extraction rates exceed considerably those achieved with the established iodinated FA [I-123]IPPA (15.5% ± 1.1).The metabolic in vivo studies reveal the complete ß-oxidation within one hour. Condition precedent for the use of the described Tc-FA in heart imaging are the improvement of the heart : liver ratio of 0.25±0.1 at 5 min p.i., which may be achieved by alterations of the FA binding mode to the “4+1” chelate unit and variations of the chelate position in the FA chain.

Literatur/References:

(1) Knapp, F. F. Jr., Kropp, J. (1995) Eur. J. Nucl. Med. 22(4), 361-381.
(2) Mach, R. H., Kung, H. F., Jungwiwattanaporn, (1991) Nucl. Med. Biol. 18, 215-226.
(3) M. Walther, C. M. Jung, R. Bergmann, (2006) Bioconjugate Chem. submitted

  • Lecture (Conference)
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A16
    ISSN: 0029-5566

Permalink: https://www.hzdr.de/publications/Publ-9748
Publ.-Id: 9748


Nierentumore zeigen nur vereinzelt einen erhöhten C-11-Azetat-Uptake in der Positronen-Emissions-Tomographie

Kotzerke, J.; Linne, C.; Meinhardt, M.; Steinbach, J.; Abolmaali, N.; Beuthien-Baumann, B.

Ziel:

Die vorliegende Arbeit untersucht das Potenzial von C-11-Azetat-Positronen-Emissions-Tomographie (PET) zur Darstellung von Nierentumoren am Menschen, da das Staging von Nierentumoren mit FDG-PET unzufriedenstellend ist.

Methodik:

Einundzwanzig Patienten mit Verdacht auf einen Nierentumor im CT/MRT wurden nach Injektion von 820±430 MBq C-11-Azetat dynamisch über 30 min untersucht (ECAT EXACT HR+, Siemens/CTI, Knoxville, USA). Die Azetat-Aufnahme wurde qualitativ auf einer 5-Punkte-Skala eingeschätzt. Die Aufnahme-Kinetik von Nierenparenchym und Tumor wurde qualitativ verglichen. Bei 18/21 Patienten erfolgte eine Operation und histologische Klassifizierung.

Ergebnisse:

Die Azetat-Aufnahme in die Tumore war geringer (n = 11), gleich (n = 8) oder höher (n = 2) als das umgebende Nierenparenchym. Bei den letztgenannten Tumoren zeigte die kinetische Analyse eine Radiotracerzunahme bis zur 10. min gefolgt von einer langsamen Tracerabnahme über den Untersuchungszeitraum. Die übrigen Tumore zeigten eine dem Nierenparenchym ähnlich Kinetik bei teilweise initial verminderter Traceraufnahme. Die Nierenfunktion war bei allen Patienten nur gering bis mäßig beeinträchtigt. Histologisch lagen klarzellige Nierenkarzinome (n = 14), zwei papilläre und zwei onkozytäre Nierentumore vor, was einer typischen Verteilung entspricht. Nur die beiden Onkozytome zeigten eine gesteigerte Azetat-Aufnahme. Diese Ergebnisse stehen im Widerspruch zur Untersuchung von Shreve et al. (1995), in der 3/3 klarzelligen Nierenkarzinomen eine erhöhte Azetat-Aufnahme aufwiesen.

Schlussfolgerungen:

Die meisten untersuchten Nierentumore zeigten keine gegenüber dem umgebenden Nierenparenchym erhöhte C-11-Azetat-Aufnahme. Die geringe C-11-Azetat-Aufnahme war nicht messtechnisch durch zu späte Akquisitionen bedingt. Auch Spätbilder zeigten keine wesentliche Kontrastzunahme. Daher kann C-11-Azetat-PET nicht routinemäßig zum Primärstaging von Nierentumoren empfohlen werden. Die Bedeutung von C-11-Azetat-PET für den Nachweis von Lymphknoten-, Fernmetastasen oder Rezidiven von Nierentumoren muß noch weiter untersucht werden.

Literatur:

Shreve P et al., J Nucl Med 36 (1995):1595-601

  • Lecture (Conference)
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A39-A40

Permalink: https://www.hzdr.de/publications/Publ-9747
Publ.-Id: 9747


Einfluss von Hypoxie und Proliferation auf die F-18-FDG-Aufnahme in 2 humanen Tumormodellen auf Nacktmäusen: Untersuchung mit PET, Autoradiographie und funktioneller Histologie

Beuthien-Baumann, B.; Gabrys, D.; Wüllrich, K.; Hofheinz, F.; Brüchner, K.; Bergmann, R.; Baumann, M.

Ziel/Aim:

Die Mehrzahl maligner Tumore weisen einen erhöhten Glukosestoffwechsel auf, ein Mechanismus der bei der Positronen-Emissions-Tomographie mit F-18-FDG in der Onkologie diagnostisch genutzt wird. Ziel dieser Untersuchung war es, die unterschiedlichen Einflüsse von Tumorhypoxie und Proliferation auf die intratumorale FDG-Aufnahme in 2 menschlichen Tumormodellen auf Nacktmäusen zu untersuchen.

Methodik/Methods:

Je 10 Nacktmäusen mit transplantiertem menschlichen Plattenepithel-Carcinom Fadu oder humanem Adeno-Carcinom HT29 wurden mit FDG und PET (MicroPET P4, CTI Molecular Imaging, gemessenen Transmission, 8 MBq FDG i.v., Untersuchung 30-60min p.i.) untersucht (Tumorvolumina 0,4 ± 0,2cc). Aus den PET-Aufnahmen wurde der SUVmax der Tumore bestimmt. Vor dem PET wurde den Mäusen Pimonidazol (Pimo) und Bromdesoxyuridin (BrdU) injiziert, die Mäuse wurden unmittelbar nach der PET getötet, die Tumore entnommen, tiefgefroren, serielle Schnitte von 20 µm angefertigt und die intratumorale FDG-Verteilung per Autoradiographie (BAS 5000, Fuji) bestimmt. Leberschnitte von 20µm dienten als Referenzgewebe. Anschließend erfolgte die Färbung der Schnitte mit Hämatoxylin/Eosin, Antikörper gegen Pimonidazol, BrdU oder Ki-67. Die Tumorschnitte wurden mit einer digitalen Kamera gescannt und per Bildanalyse wurden Masken für vitalen Tumor, Nekrose und funktionelle Färbungen (Pimo, BrdU, Ki-67) angefertigt. Die digitalen Histologien wurden mit der korrespondierenden Autoradiographie koregistriert und die quantitative FDG-Aufnahme in den definierten Tumorarealen bestimmt.

Ergebnisse/Results:

Der SUVmax in Fadu (1,55 ± 0,26) lag etwas höher als in HT29 (1,30 ± 0,17; p=0,03). Fadu bildet größere hypometabole Bereich aus, die sich in der Histologie als Nekrose identifizieren liessen. Bei ähnlicher Größe der Pimo-positiven Areale in Fadu und HT29 fand sich nur in Fadu eine signifikant höhere FDG-Aufnahme in den hypoxischen Arealen im Vergleich zu vitalem Pimo-negativem Tumorgewebe (Fadu: 3,1 ± 0,2 versus 2,2 ± 0,2 %ID/g, p=0,002, HT29: 2,4 ± 0,2 versus 2,2 ± 0,2%ID/g, p=0,4). In beiden Tumormodellen fand sich keine regional erhöhte FDG-Aufnahme in Tumorregionen mit proliferativer Aktivität im Vergleich zu nicht in Teilung begriffenen vitalen Tumorarealen.

Schlussfolgerungen/Conclusions:

In den zwei untersuchten Tumormodellen war nur bei dem Plattenepithel-Ca Fadu ein Einfluß der Hypoxie auf die FDG-Aufnahme zu erkennen, die höhere FDG-Aufnahme in Hypoxiearealen könnte sich in dem höheren SUVmax im Vergleich zum Adeno-Ca HT29 widerspiegeln. Weder in Fadu noch in HT29 fand sich eine Korrelation zwischen Proliferation (BrdU, Ki-67) und Intensität der FDG-Aufnahme.

Die Daten wurden im Rahmen des 6.Rahmenprogrammes der EU, Projekt Biocare, proposal Nr. 505785, erhoben.

  • Lecture (Conference)
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A14
    ISSN: 0029-5566

Permalink: https://www.hzdr.de/publications/Publ-9746
Publ.-Id: 9746


Untersuchung des Einflusses von Kopfbewegungen auf die Quantifizierung von FDOPA-PET-Studien

Oehme, L.; Beuthien-Baumann, B.; Bühler, P.; Langner, J.; Pötzsch, C.; Hofheinz, F.; van den Hoff, J.

Ziel/Aim:

Ziel war die Bestimmung des Einflusses von Kopfbewegungen während einer dynamischen Untersuchung auf die Kompartmentmodell-gestützte Quantifizierung des FDOPA Uptakes durch den Vergleich von Auswertungen der bewegungskorrigierten und der unkorrigierten Daten.

Methodik/Methods:

Retrospektiv wurden Daten von 57 Patienten (32 m, 25 w, mittleres Alter 58,8 Jahre) analysiert, welche im Rahmen der Parkinson-Diagnostik mit F-18-FDOPA eine PET-Untersuchung (EXACT HR+, Siemens) erhielten. Die Messung erfolgte im Listmode, daraus wurde eine dynamische Studie von 21 Frames erstellt. Parallel zur Aufnahme wurde die Kopfbewegung mit einem Motion-Tracking-System (A.R.T.,München) aufgezeichnet. Die Bewegungsdaten wurden detailliert analysiert und zur Korrektur der Emissionsbilder verwendet. Dopamin-Einstromraten für die korrigierten und unkorrigierten Studien wurden mittels grafischer Patlak-Analyse sowohl für 8 manuell positionierte striatale VOIs (0,35ml, Software: ROVER, abx biochemicals) als auch voxelweise quantifiziert (Referenzregion okzipitaler Cortex, Regression 15-60min) und verglichen.

Ergebnisse/Results:

Bei 2 Patienten wurde ein Versagen der Bewegungskorrektur festgestellt, was auf eine ungenügende Fixierung des Targets für die Bewegungsmessung am Patientenkopf zurückgeführt wurde. Über das Kollektiv betrachtet sind die Bewegungen klein: Median und Quantilen (10%-90%) Translationen in mm für x;y;z 1,6 (0,8-3,4); 1,8 (1,0-4,7); 2,8 (1,0-8,0); Rotation in Grad um x;y;z-Achse 2,2 (1,2-4,9); 0,8 (0,4-1,7); 0,6 (0,3-1,7). Daraus ergeben sich maximale Voxelverschiebungen innerhalb des Gehirns von: weniger als 4mm bei 24 Patienten, zwischen 4 und 8mm bei 20 Patienten und 10mm bei einem Patienten. Die Verteilung des prozentualen Unterschiedes der Einstromraten ohne und mit Korrektur für die 440 VOIs hat einen Median von 1%. 80% der Werte liegen zwischen -4% und 13,6%. Bei 11 Patienten finden sich Abweichungen von mehr als 20% (Absolutbetrag), wobei bei 3 Patienten mehr als 3 VOIs betroffen sind. Dies sind Patienten, welche sich insbesondere in z-Richtung stark bewegt haben (>11mm). Kopfbewegung während der Aufnahme führt meist zu einer Überschätzung der Einstromraten, was sich auch in den Histogrammen der voxelweise korrelierten parametrischen Bilder zeigt. Artefakte in den parametrischen Bildern sind am ehesten in den kortikalen Bereichen erkennbar.

Schlussfolgerungen/Conclusions:

Bei der Quantifizierung der Dopamin-Einstromraten sollte eine Bewegungskorrektur angestrebt werden. Die hier angewandte framebasierte Methode ist einfach und schnell anwendbar, weitere Verbesserungen sollten durch eventbasierte Korrektur der Emission und Einrechnung von korrigierten Transmissionsdaten erreichbar sein.

  • Poster
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A118
    ISSN: 0029-5566

Permalink: https://www.hzdr.de/publications/Publ-9745
Publ.-Id: 9745


Implementierung von Methoden zur Integration der PET in die Bestrahlungsplanung

Hofheinz, F.; Pötzsch, C.; Oehme, L.; van den Hoff, J.

Ziel/Aim:

Die Integration der PET in die Bestrahlungsplanung ist für die Strahlentherapie von zunehmendem Interesse. Folgende Voraussetzungen sind hierfür zu erfüllen: 1) adäquate DICOM-Integration der PET (Herstellerseitig für neuere Geräte i.w. erfüllt), 2) volumetrisch korrekte und routinefähige 3D ROI-Abgrenzung in den PET-Daten, 3) Transfer der 3D-ROIs in den DICOM-RT Standard, 4) Koregistrierung PET vs. Bestrahlungsplanungs-CT. Ziel dieser Arbeit war die vollständige Implementierung eines routinefähigen Workflows unter Nutzung existierender und neu entwickelter Methoden.

Methodik/Methods:

Die genutzten Verfahren zur benutzerunabhängigen 3D-ROI-Definition und Koregistrierung wurden anderweitig bereits vorgestellt (1-3). Umgesetzt wurde nunmehr die fehlende Übersetzung der resultierenden 3D-ROIs in den DICOM-RT Standard als Voraussetzung für den Import der ROIs in die Bestrahlungsplanungssysteme sowie die Kombination der verschiedenen Arbeitsschritte in einen routinefähigen Ablauf unter Nutzung einer eigenen DICOM-Schnittstelle. Das gesamte Verfahren wurde an verschiedenen Bestrahlungsplanungssystemen getestet.

Ergebnisse/Results:

Die PET-Information konnte in Planungssysteme verschiedenerer Hersteller integriert werden, wobei der Integrations-Workflow teilweise an das jeweilige Planungssystem angepasst werden musste. Unser Verfahren erlaubt insbesondere auch die Kombination der PET-ROIs und die Planungs-CT Konturen, was die Handhabung der kombinierten Information auf den Planungssystemen erleichtert. Der durch die Integration verursachte zusätzliche zeitliche Aufwand bei der Auswertung der PET-Aufnahmen ist vernachlässigbar.

Schlussfolgerungen/Conclusions:

Die vorgestellte Methode erlaubt eine routinemäßige Integration der PET-Information in die Bestrahlungsplanung.

Literatur/References:

1. C. Pötzsch;F. Hofheinz;J. van den Hoff; Nuklearmedizin (2005) 44 p. A16
2. C. Pötzsch;F. Hofheinz;J. van den Hoff; Nuklearmedizin (2006) 45 p. A42
3. F. Hofheinz;C. Pötzsch;J. van den Hoff; Nuklearmedizin (2005) 44 p. A162

  • Lecture (Conference)
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A10

Permalink: https://www.hzdr.de/publications/Publ-9744
Publ.-Id: 9744


Koregistrierung parametrischer PET-Daten mit CT-Datensätzen in der kardialen Diagnostik

Fricke, H.; Schwier, M.; Weise, R.; Fricke, E.; van den Hoff, J.; Domik, G.; Burchert, W.

Ziel/Aim:

Die kardiale PET zeichnet sich gegenüber der SPECT u. a. durch die Möglichkeit der absolut quantifizierenden Messung der myokardialen Perfusion aus. In der Diagnostik der KHK wird zunehmend eine Kombination von SPECT oder PET mit einer morphologischen Darstellung der Koronargefäße durch eine CT-Angiographie eingesetzt. Auch bei Einsatz von Hybridgeräten machen Unterschiede in der Datenakquisition und die Thoraxbewegung bei der Atmung eine Koregistrierung der Datensätze erforderlich. Von Seiten der Gerätehersteller wird derzeit jedoch nur eine Koregistrierung statischer Datensätze unterstützt. Der wesentliche Vorteil der PET, die Einschätzung einer koronaren 3-Gefäßerkrankung durch Beurteilung der absoluten Flusswerte, geht dadurch verloren. Ziel war daher die Koregistierung von CT und funktionellem PET-Datensatz.

Methodik/Methods:

Verwendet wurden dynamische PET-Studien mit N-13-Ammoniak und CT-Angiographien der Koronargefäße, die an unabhängigen Geräten akquiriert wurden. Die Koregistrierung von CT und PET erfolgte anhand des rekonstruierten CT-Datensatzes und des PET-Uptake-Bildes (letztes Frame der dynamischen Studie, 9.-16. Minute). Die Koregistrierung erfolgte manuell sowie durch automatische Detektion von Grenzflächen über Schwellenwerte. Im Rahmen der Kompartmentmodellierung dynamischer PET-Datensätze findet eine Reorientierung entsprechend der Herzachsen statt und die funktionellen Parameter können nur für Volumenelemente innerhalb des Myokards bestimmt werden. Daher gehen die ursprüngliche Orientierung der Datensätze und weitergehende anatomische Informationen zunächst verloren. Für eine kombinierte Darstellung der Morphologie der Koronargefäße und der quantitativen Flussinformation wurde daher in einem nächsten Schritt eine Rückprojektion der Flussinformation in die anatomisch korrekte Lokalisation durchgeführt.

Ergebnisse/Results:

Mit der vorliegenden Methode ist es möglich, quantitative Flussinformationen aus der PET mit CT-Angiographien der Koronargefäße zu koregistrieren und somit im Kontext anatomischer Daten darzustellen. Dies bedeutet für die klinische Anwendung, dass es im Vergleich zur myokardialen SPECT/CT möglich ist, relevante Hauptstammstenosen zu erkennen und auch bei koronarer Mehrgefäßerkrankung nicht nur die funktionelle Relevanz der führenden, sondern aller Stenosen zu beurteilen.

Schlussfolgerungen/Conclusions:

Die Weiterentwicklung von Software, die eine Koregistrierung von morphologischen Daten aus der CT und funktionellen Daten aus der PET ohne Informationsverluste ermöglicht, ist insbesondere im Hinblick auf die zunehmende Häufigkeit von Hybridgeräten dringend erforderlich.

  • Lecture (Conference)
    45. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, 25.-28.04.2007, Hannover, Deutschland
  • Abstract in refereed journal
    Nuklearmedizin 46(2007), A32

Permalink: https://www.hzdr.de/publications/Publ-9743
Publ.-Id: 9743


First in-beam PET measurement of β+ radioactivity induced by hard photon beams

Kluge, T.; Möckel, D.; Pawelke, J.; Enghardt, W.

In this article we present the first experimental results of in-beam PET measurements during high energy photon phantom irradiation. An inhomogeneous phantom was irradiated with pulsed 34 MV bremsstrahlung. The measurements have been conducted with a dedicated double head photon camera. A high material contrast could be achieved and furthermore production rates of C-11 and O-15 were derived from the time dependent activity.

Permalink: https://www.hzdr.de/publications/Publ-9742
Publ.-Id: 9742


Binding Studies of 14C-Caffeine to Artificial Receptors

Waldvogel, S. R.; Bomkamp, M.; Siering, C.; Malkowsky, I.; Landrock, K.; Stephan, H.

Caffeine is among the most frequently consumed alkaloidal compounds and is omnipresent in many plants. The traditional significant sources of caffeine in daily life are coffee, black tea and cocoa. Actually, the alkaloid is an ingredient of Cola beverages and energy drinks. Many analgesics sold-over-the-counter contain also caffeine. Because of the wide range of applications and the potential of new analytical tools caffeine is currently gathering an increasing attention. Recently, we reported the synthesis of functionalized triphenylene ketals which represent the rigid C3v symmetric scaffold of our novel receptors (1). The cleft like structure exhibits a high affinity to caffeine and does not interfere with the alkyl groups of the oxopurine system leading to a novel concept for the molecular recognition of caffeine and related compounds. Based on this concept several methods for the detection of caffeine in real life samples have been established. With extraction studies using 14C-labelled caffeine the potential of this receptor systems and their binding action could be elucidated. This is a key prerequisite for the further development of caffeine detection systems on a dip-stick model. Furthermore, first experiments were done in view of the development of controlled release systems for caffeine in aqueous media.

  • Lecture (Conference)
    14th Workshop der International Isotope Society, 21.-22.06.2007, Bad Soden, Germany
  • Abstract in refereed journal
    Journal of Labelled Compounds and Radiopharmaceuticals 50(2007), 1280-1282
    ISSN: 0362-4803

Permalink: https://www.hzdr.de/publications/Publ-9741
Publ.-Id: 9741


Efficient melt stirring using pulse sequences of a rotating magnetic field: I - Flow field in a liquid metal column

Eckert, S.; Nikrityuk, P. A.; Räbiger, D.; Eckert, K.; Gerbeth, G.

The utilization of a pulsed rotating magnetic field (RMF) is presented as an auspicious method to obtain an intensive stirring and mixing in a pool of liquid metal. The RMF pulses within a sequence have been applied with constant or alternating direction, respectively. The resulting flow structure in a cylindrical liquid metal column has been explored by numerical simulations and by model experiments using the ternary alloy GaInSn. The ultrasonic Doppler velocimetry (UDV) has been used to determine profiles of the vertical velocity. The numerical results as well as the velocity measurements demonstrate the capability of the proposed stirring regimes to overcome the limited mixing character of conventional rotary stirring. The application of a time-modulated RMF offers a considerable potential to provide optimal flow pattern in a solidifying melt for reasons of a well-aimed modification of casting properties.

Keywords: electromagnetic stirring; rotating magnetic field; Ultrasonic Doppler Velocimetry; solidification

Permalink: https://www.hzdr.de/publications/Publ-9740
Publ.-Id: 9740


Synthesis of an 11C-labelled cyclooxygenase-2 (COX-2) inhibitor and PET imaging in HT-29 and FaDu tumor bearing mice

Knieß, T.; Bergmann, R.; Wüst, F.

Cyclooxygenase-2 (COX-2) is an enzyme induced during inflammation by various stimuli, but overexpression of COX-2 has been observed also in oncogenesis in a variety of tumors. Although several COX-2 inhibitors have recently been radiolabeled with isotopes for positron emission tomography (PET), their potential for tumor imaging has not been explored extensively. Herein we report the synthesis and radiopharmacological evaluation of 1-(4-[11C]methoxyphenyl)-2-(4-methylsulfonylphenyl)-1-cyclopentene as novel 11C-labelled radiotracer for PET imaging of COX-2.

Methods:

The radiolabeling was performed via a 11C-methylation reaction of the corresponding desmethyl precursor using [11C]MeI in a TRACERLab FXC module.
Biodistribution studies were performed in normal Wistar rats. Small animal PET studies were performed using xenografted HT-29 and FaDu tumors in mice using a micro-PET® P4 scanner.

Results:

The radiolabeling was achieved by the reaction of 1-(4-hydroxyphenyl)-2-(4-methylsulfonylphenyl)-1-cyclopentene at 60°C in DMF/aqueous NaOH with [11C]CH3I. After semi-preparative HPLC purification and solid phase extraction the 11C-labelled COX-2 inhibitor was obtained in 12-14 % decay-corrected radiochemical yield at a specific activity of 30 GBq/µmol at the end-of-synthesis. The radiochemical purity exceeded 97%. Biodistribution in normal rats showed high radioactivity accumulation in the liver, adrenals and brown adipose tissue, reaching 0.6±0.1, 0.7±0.2 and 0.8±0.1 %ID/g after 1 h post injection, respectively. Tumor-to-muscle ratios of 1.7±0.2 and 2.1±0.3, respectively, were determined with small animal PET-studies of xenografted HT-29 and FaDu tumors in mice after 1 h post injection.

  • Poster
    2nd International Conference of the European Society for Molecular Imaging, 14.-15.06.2007, Naples, Italy

Permalink: https://www.hzdr.de/publications/Publ-9739
Publ.-Id: 9739


Modified “4+1” Mixed Ligand Technetium Labeled Fatty Acids for Myocardial Imaging: Evaluation of Myocardial Uptake and Biodistribution

Mirtschink, P.; Stehr, S. N.; Pietzsch, H.-J.; Bergmann, R.; Pietzsch, J.; Wunderlich, G.; Heintz, A. C.; Kropp, J.; Spies, H.; Kraus, W.; Deussen, A.; Walther, M.

Our group previously synthesized 99mTc-labeled fatty acids suitable for myocardial metabolism and flow imaging. In this set of experiments 28 new analogues were synthesized according to the “4+1” mixed ligand approach with some specific differences. Conventional “4+1” 99mTc-fatty acids are built in the sequence Tc-chelate, alkyl chain and carboxylic group. We developed compounds with a new design with the sequence carboxylic group, alkyl chain, Tc-chelate, and lipophilic tail. Therefore the 99mTc-chelate was transferred to a more central position of the compound, aiming towards an improved myocardial profile and an accelerated liver clearance. In this context several functional groups incorporated in the lipophilic tail section were tested to evaluate their influence on the compound’s character. In addition to biodistribution studies in vivo the myocardial first-pass extraction of the compounds was tested in an isolated Langendorff rat heart model. A satisfactory myocardial uptake up to 20% of the injected dose (% ID) in the perfused heart and a fast liver clearance in vivo with only 0.29% ID/g at 60 min post injection demonstrates that the induced molecular modifications affect the kinetics of 99mTc-radiolabeled fatty acid compounds favorably. From the data set rules for estimating the biodistribution of fatty acids tracers are deduced.

Permalink: https://www.hzdr.de/publications/Publ-9738
Publ.-Id: 9738


First results in 64Cu-production and copper complexation by new ligands derived from bispidine and 1,4,7-triazacyclononane

Walther, M.; Preusche, S.; Gasser, G.; Tjioe, L.; Graham, B.; Spiccia, L.; Juran, S.; Künstler, J.-U.; Stephan, H.; Steinbach, J.

Introduction:

64Cu (t1/2 = 12.7 h; ß+ 0.653 MeV, 17.4%; ß-: 0.578 MeV, 39%) [1,2] is the most used copper isotope in nuclear medicine due to its favorable decay characteristics and its ability to be produced with high specific activity. Bispidines and azamacrocycles containing pyridine pendant arms form thermodynamically stable complexes with copper(II) [1,2]. These chelating agents – possessing an additional linker group – provide an attractive lead for labelling biomolecules with copper radionuclides.

Experimental:

First experiments to adapt the described 64Cu-production process [3,4] at a biomedical cyclotron CYCLONE 18/9 were performed. A bombarding energy of 10 MeV and a proton beam current of 10 µA for 15 to 60 min were used. The yields of the 64Ni(p,n)64Cu reaction were comparable to reference values [179-331 MBq/µA/h versus 185-248 MBq/µA/h [3,4]].
Two novel ligands with carboxylic groups – a hexadentate bispidine 1 and a derivative of 1,4,7-triazacyclononane (TACN) 2 [5] were prepared. Labelling experiments of these ligands indicated the rapid formation of stable 64Cu-complexes under mild conditions. The bioconjugates 3 and 4 were obtained by coupling the bombesin (BBN) derivate βAla-βAla-[Cha13, Nle14]BBN(7-14) [6] to the ligands 1 and 2 (HBTU, DIPEA, DMF, r.t.).

Results and Discussion:
The bioconjugation of 1 and 2 to a bombesin derivative was successfully achieved via amide coupling to give 3 and 4. The free ligands and the bioconjugates were labelled with 64Cu and the resulting complexes were found to be stable in the presence of a large excess of competing ligands such as cyclam and even in rat plasma.

Conclusion:

The bispidine ligand 1, the TACN derivative 2 and their bombesin bioconjugates 3 and 4 are able to form complexes with high stability. These bifunctional chelating agents may be attractive candidates for the development of new copper radiopharmaceuticals for diagnosis (64Cu) and therapy (67Cu). Preliminary studies on the bio-distribution of 64Cu-complexes of 3 and 4 are currently underway [5].

[1] C. Bleiholder et al., Inorg. Chem. 2005, 44, 8145-8155.
[2] G. A. McLachlan et al., Inorg. Chem. 1994, 33, 4663-4668.
[3] F. Szelecsényi et al., Appl. Radiat. Isotopes 1993, 44, 575-580.
[4] D. W. McCarthy et al., Nucl. Med. Biol. 1997, 24, 35–43.
[5] G. Gasser et al., Bioconjugate Chemistry, 2007, in prep.
[6] E. Garcia Garayoa et al., Nucl. Med. Biol. 2007, 34, 17-28.

  • Lecture (Conference)
    2nd International Conference on Radiopharmaceutical Therapy, 03.-07.09.2007, Ulaanbaatar, Mongolia

Permalink: https://www.hzdr.de/publications/Publ-9737
Publ.-Id: 9737


Diagnostics Beamline for the SRF Gun Project

Kamps, T.; Dürr, V.; Goldammer, K.; Krämer, D.; Kuske, P.; Kuszynski, J.; Lipka, D.; Marhauser, F.; Quast, T.; Richter, D.; Lehnert, U.; Michel, P.; Teichert, J.; Evtushenko, P.

A superconducting radio-frequency photo electron injector (SRF gun) is currently under construction by a collaboration of BESSY, DESY, FZR and MBI. The project aims at the design and setup of a CW SRF gun including a diagnostics beamline for the ELBE FEL and to address R&D issues on low emittance injectors for future light sources such as the BESSY FEL. Of critical importance for the injector performance is the control of the electron beam parameters. For this reason a compact diagnostics beamline is under development serving a multitude of operation settings ranging from low-charge (77pC), low-emittance (1 mm mrad) mode to high-charge (2.5nC) operation of the gun. For these operation modes beam dynamics simulations are resulting in boundary conditions for the beam instrumentation. Proven and mature technology is projected wherever possible, for example for current and beam position monitoring. The layout of the beam profile and emittance measurement systems is described. For the bunch length, which varies between 5 ps and 50 ps, two schemes using electro-optical sampling and Cherenkov radiation are detailed. The beam energy and energy spread is measured with a 180o spectrometer.

  • Contribution to proceedings
    27th International Free Elektron Laser Conference FEL 2005, 21.-26.08.2005, Stanford, CA, USA
    Proceedings of the 27th International Free Electron Laser Conference 2005, 530-533

Downloads

Permalink: https://www.hzdr.de/publications/Publ-9736
Publ.-Id: 9736


Status of the 7Be(p,g)8B S-factor

Junghans, A.

We present new measurements of the 7Besp,gd8B cross section from Ec.m.=116 to 2460 keV (where c.m. means center-of-mass), which incorporate several improvements over our previously published experiment, also discussed here. Our new measurements lead to S17s0d=22.1±0.6sexptd±0.6stheord eV b based on data from Ec.m.=116 to 362 keV, where the central value is based on the theory of Descouvemont and Baye. The theoretical error estimate is based on the fit of 12 different theories to our low-energy data. We compare our results to other S17s0d values extracted from both direct f7Besp,gd8Bg and indirect (Coulomb-dissociation and heavy-ion reaction) measurements, and show that the results of these three types of experiments are not mutually compatible. We recommend a “best” value, S17s0d=21.4±0.5sexptd±0.6stheord eV b, based on the mean of all modern direct measurements below the 1+ resonance. We also present S factors at 20 keV which is near the center of the Gamow window: the result of our measurements is S17s20d =21.4±0.6sexptd±0.6stheord eV b, and the recommended value is S17s20d=20.6±0.5sexptd±0.6stheord eV b.

  • Invited lecture (Conferences)
    Advances and Challenges in Nuclear Astrophysics, 24.05.2004, Trento, Italy

Permalink: https://www.hzdr.de/publications/Publ-9735
Publ.-Id: 9735


Precise measurement of the 7Be(p,g)8B S-factor

Junghans, A.

We present new measurements of the 7Besp,gd8B cross section from Ec.m.=116 to 2460 keV (where c.m. means center-of-mass), which incorporate several improvements over our previously published experiment, also discussed here. Our new measurements lead to S17s0d=22.1±0.6sexptd±0.6stheord eV b based on data from Ec.m.=116 to 362 keV, where the central value is based on the theory of Descouvemont and Baye. The theoretical error estimate is based on the fit of 12 different theories to our low-energy data. We compare our results to other S17s0d values extracted from both direct f7Besp,gd8Bg and indirect (Coulomb-dissociation and heavy-ion reaction) measurements, and show that the results of these three types of experiments are not mutually compatible. We recommend a “best” value, S17s0d=21.4±0.5sexptd±0.6stheord eV b, based on the mean of all modern direct measurements below the 1+ resonance. We also present S factors at 20 keV which is near the center of the Gamow window: the result of our measurements is S17s20d =21.4±0.6sexptd±0.6stheord eV b, and the recommended value is S17s20d=20.6±0.5sexptd±0.6stheord eV b.

  • Invited lecture (Conferences)
    Bothe Kolloquium, 19.5.2004, Heidelberg, Deutschland

Permalink: https://www.hzdr.de/publications/Publ-9734
Publ.-Id: 9734


Combined TEM, PAS and SANS investigation of neutron-irradiated pure iron

Bergner, F.; Al Mazouzi, A.; Hernandez-Mayoral, M.; Ulbricht, A.

Fission spectrum neutron irradiation of pure Fe at irradiation temperatures of about 300 °C gives rise to the formation of two populations of defects: planar dislocation loops and spherical vacancy-type clusters. Knowledge of the type and size distributions of these populations is important for the purpose of multi-scale modelling of the mechanical behaviour of Fe-based alloys. Among the experimental techniques with nanometer size resolution, transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) allow to gain information on both nature and size distribution of particular types of defects. Furthermore, positron annihilation spectroscopy (PAS) is sensitive to sub-nanometer size open-volume defects. However, there is no single experimental technique capable of providing the full set of information required for calibration and validation of advanced models. The complementarity between the three techniques to identify and quantify the defects created by irradiation in pure Fe is emphasised in the paper. It is shown that while TEM allows direct size-resolved evidence of dislocation loops, PAS a qualitative appreciation of the existing sub-nanometer size vacancy-type clusters, SANS yields indirect size-resolved evidence of vacancy-type clusters, which form a sound basis for the quantification of the size distributions.

  • Lecture (Conference)
    Workshop on Structural Materials for Innovative Nuclear Systems (SMINS), 04.-06.06.2007, Karlsruhe, Germany
  • Contribution to proceedings
    Structural Materials for Innovative Nuclear Systems (SMINS), 04.-06.06.2007, Karlsruhe, Germany
    Workshop Proceedings: OECD 2008, 283-290

Permalink: https://www.hzdr.de/publications/Publ-9733
Publ.-Id: 9733


Spallation residues in the reaction 56Fe+ p at 0.3A, 0.5A, 0.75A, 1.0A, and 1.5A GeV

Villagrasa-Canton, C.; Boudard, A.; Ducret, J.-E.; Fernandez, B.; Leray, S.; Volant, C.; Armbruster, P.; Enqvist, T.; Hammache, F.; Helariutta, K.; Jurado, B.; Ricciardi, M. V.; Schmidt, K.-H.; Sümmerer, K.; Vives, F.; Yordanov, O.; Audouin, L.; Bacri, C.-O.; Ferrant, L.; Napolitani, P.; Rejmund, F.; Stephan, C.; Tassan-Got, L.; Benlliure, J.; Casarejos, E.; Fernandez-Ordonez, M.; Pereira, J.; Czajkowski, S.; Karamanis, D.; Pravikoff, M.; George, J. S.; Mewaldt, R. A.; Yanasak, N.; Wiedenbeck, M.; Connell, J. J.; Faestermann, T.; Heinz, A.; Junghans, A.

The spallation residues produced in the bombardment of 56Fe at 1.5A, 1.0A, 0.75A, 0.5A, and 0.3A GeV on a liquid-hydrogen target have been measured using the reverse kinematics technique and the fragment separator at GSI (Darmstadt). This technique has permitted the full identification in charge and mass of all isotopes produced with cross sections larger than 10−2 mb down to Z = 8. Their individual production cross sections and recoil velocities at the five energies are presented. Production cross sections are compared with previously existing data and with empirical parametric formulas, often used in cosmic-ray astrophysics. The experimental data are also extensively compared with the results of different combinations of intranuclear cascade and deexcitation models. It is shown that the yields of the lightest isotopes cannot be accounted for by standard evaporation models. The GEMINI model, which includes an asymmetric fission decay mode, gives an overall good agreement with the data. These experimental data can be directly used for the estimation of composition modifications and damages in materials containing iron in spallation sources. They are also useful for improving high-precision cosmic-ray measurements.

Permalink: https://www.hzdr.de/publications/Publ-9732
Publ.-Id: 9732


X-ray diffraction study of low-energy carbon-ion implanted Si(001)

Markwitz, A.; Barry, B.; Eichhorn, F.

In the search for Si- and C-based crystalline phases in low-energy ion implanted and electron-beam annealed Si surface layers, X-ray diffraction (XRD) measurements were performed at grazing incidence on samples of large SiC nanocrystals grown on a 90 nm thick Si layer containing C atoms. Diffraction patterns and reciprocal space maps did not reveal XRD patterns originating from the nanocrystals or the implanted layer, but did show that distortions of the Si crystal structure were introduced into the implanted layer. After annealing, the strain in the implanted layer is reduced, possibly by carbon atoms that have moved to locations close to dislocations and dislocation loops. This investigation underpins the growth theory of the SiC nanocrystals on Si, with carbon atoms migrating to form the nanostructures.

  • Surface and Interface Analysis 39(2007)5, 415-418

Permalink: https://www.hzdr.de/publications/Publ-9731
Publ.-Id: 9731


Pages: [1.] [2.] [3.] [4.] [5.] [6.] [7.] [8.] [9.] [10.] [11.] [12.] [13.] [14.] [15.] [16.] [17.] [18.] [19.] [20.] [21.] [22.] [23.] [24.] [25.] [26.] [27.] [28.] [29.] [30.] [31.] [32.] [33.] [34.] [35.] [36.] [37.] [38.] [39.] [40.] [41.] [42.] [43.] [44.] [45.] [46.] [47.] [48.] [49.] [50.] [51.] [52.] [53.] [54.] [55.] [56.] [57.] [58.] [59.] [60.] [61.] [62.] [63.] [64.] [65.] [66.] [67.] [68.] [69.] [70.] [71.] [72.] [73.] [74.] [75.] [76.] [77.] [78.] [79.] [80.] [81.] [82.] [83.] [84.] [85.] [86.] [87.] [88.] [89.] [90.] [91.] [92.] [93.] [94.] [95.] [96.] [97.] [98.] [99.] [100.] [101.] [102.] [103.] [104.] [105.] [106.] [107.] [108.] [109.] [110.] [111.] [112.] [113.] [114.] [115.] [116.] [117.] [118.] [119.] [120.] [121.] [122.] [123.] [124.] [125.] [126.] [127.] [128.] [129.] [130.] [131.] [132.] [133.] [134.] [135.] [136.] [137.] [138.] [139.] [140.] [141.] [142.] [143.] [144.] [145.] [146.] [147.] [148.] [149.] [150.] [151.] [152.] [153.] [154.] [155.] [156.] [157.] [158.] [159.] [160.] [161.] [162.] [163.] [164.] [165.] [166.] [167.] [168.] [169.] [170.] [171.] [172.] [173.] [174.] [175.] [176.] [177.] [178.] [179.] [180.] [181.] [182.] [183.] [184.] [185.] [186.] [187.] [188.] [189.] [190.] [191.] [192.] [193.] [194.] [195.] [196.] [197.] [198.] [199.] [200.] [201.] [202.] [203.] [204.] [205.] [206.] [207.] [208.] [209.] [210.] [211.] [212.] [213.] [214.] [215.] [216.] [217.] [218.] [219.] [220.] [221.] [222.] [223.] [224.] [225.] [226.] [227.] [228.] [229.] [230.] [231.] [232.] [233.] [234.] [235.] [236.] [237.] [238.] [239.] [240.] [241.] [242.] [243.] [244.] [245.] [246.] [247.] [248.] [249.] [250.] [251.] [252.] [253.] [254.] [255.] [256.] [257.] [258.] [259.] [260.] [261.] [262.] [263.] [264.] [265.] [266.] [267.] [268.] [269.] [270.] [271.] [272.] [273.] [274.] [275.] [276.] [277.] [278.] [279.] [280.] [281.] [282.] [283.] [284.] [285.] [286.] [287.] [288.] [289.] [290.] [291.] [292.] [293.] [294.] [295.] [296.] [297.] [298.] [299.] [300.] [301.] [302.] [303.] [304.] [305.] [306.] [307.] [308.] [309.] [310.] [311.] [312.] [313.] [314.] [315.] [316.] [317.] [318.] [319.] [320.] [321.] [322.] [323.] [324.] [325.] [326.] [327.] [328.] [329.] [330.] [331.] [332.] [333.] [334.] [335.] [336.] [337.] [338.] [339.] [340.] [341.] [342.] [343.] [344.] [345.] [346.] [347.] [348.] [349.]