TY - JOUR A1 - Drews, A. A1 - Pietzsch, H.-J. A1 - Syhre, R. A1 - Seifert, S. A1 - Varnäs, K. A1 - Hall, H. A1 - Halldin, C. A1 - Kraus, Werner A1 - Karlsson, P. T1 - Synthesis and biological evaluation of technetium(III) mixed-ligand complexes with high affinity for the cerebral 5-HT1A receptor and the alpha-1-adrenergic receptor N2 - Tc(III) and Re(III) complexes [M(NS3)(CNR)] (M = Re, 99mTc, NS3 = 2,2?,2?-nitrilotris(ethanethiol), CNR = functionalized isocyanide bearing a derivative of WAY 100635) have been synthesized and characterized. Re was used as Tc surrogate for chemical characterization and in vitro receptor-binding studies. For two representatives subnanomolar affinities for the 5-HT1A as well as for the alpha1-adrenergic receptor were reached. Biodistribution studies in rats of the 99mTc complexes showed brain uptakes between 0.3 and 0.5% ID/organ (5 min p.i.). In vitro autoradiography of one 99mTc representative in sections of post mortem human brain indicate its accumulation in 5-HT1A receptor-rich brain regions. However, addition of the specific 5-HT1A receptor agonist 8-OH-DPAT as well as the alpha1-adrenoceptor antagonist prazosin could not substantially block this tracer accumulation. A preliminary SPET study in a monkey showed negligible brain uptake. KW - 5-HT1A receptor KW - Alpha 1-adrenergic receptor KW - Technetium-99m KW - Rhenium KW - Autoradiography KW - SPET PY - 2002 DO - https://doi.org/10.1016/S0969-8051(02)00296-2 SN - 0883-2897 VL - 29 IS - 4 SP - 389 EP - 398 PB - Elsevier Science Inc. CY - New York, NY AN - OPUS4-1553 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Heimbold, I. A1 - Drews, A. A1 - Kretzschmar, M. A1 - Varnäs, K. A1 - Hall, H. A1 - Halldin, C. A1 - Syhre, R. A1 - Kraus, Werner A1 - Pietzsch, H.-J. T1 - Synthesis, Biological and Autoradiographic Evaluation of a Novel Tc-99m Radioligand derived from WAY 100635 with High Affinity for the 5-HT1A Receptor and the alpha1-Adrenergic Receptor N2 - This paper reports the synthesis, biological evaluation, in vitro and ex vivo autoradiography of the first Tc-99m ligand with subnanomolar affinity for the 5-HT1A receptor and a remarkably high affinity for the alpha1-adrenergic receptor. The neutral “3+1” mixed-ligand complex combines 4-(6-mercaptohexyl)-1-(2-methoxyphenyl)piperazine as monodentate and 3-(N-methyl)azapentane-1,5-dithiol as tridentate unit with oxotechnetium(V). The analogous rhenium complex was synthesized for complete structural characterization and used in receptor binding assays. In competition experiments both complexes display subnanomolar affinity for the 5-HT1A receptor (IC500.24 nM for Re, 0.13 nM for Tc) but also very high affinities for the alpha1-adrenergic receptor (IC50 0.05 nM for Re, 0.03 nM for Tc). Biodistribution studies show a brain uptake in rat of 0.22% ID five minutes post injection. In vitro autoradiographic studies in rat brain and postmortem human brain indicate accumulation of the Tc-99m complex in brain areas which are rich in 5-HT1A receptors or in alpha1-adrenergic receptors. This in vitro enrichment can be blocked respectively by the 5-HT1A receptor agonist 8-OH-DPAT or by prazosin hydrochloride, an alpha1-adrenergic receptor antagonist. Ex vivo autoradiographic studies in rats show a slight accumulation of the Tc-99m complex in 5-HT1A receptor-rich areas of the brain, which could not be blocked, as well as in regions rich in alpha1-adrenergic receptors, which could be blocked by prazosin hydrochloride. KW - Serotonin-5-HT1A receptor KW - Tc-99m receptor ligand KW - WAY100635 analogue KW - Ligand synthesis KW - In vitro and ex vivo autoradiography KW - Receptor binding assay PY - 2002 DO - https://doi.org/10.1016/S0969-8051(01)00313-4 SN - 0883-2897 VL - 29 SP - 375 EP - 387 PB - Elsevier Science Inc. CY - New York, NY AN - OPUS4-1554 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Lay, Vera A1 - Buske, S. A1 - Townend, J. A1 - Kellett, R. A1 - Savage, M. A1 - Schmitt, D. R. A1 - Constantinou, A. A1 - Eccles, J. D. A1 - Gorman, A. A1 - Bertram, M. A1 - Hall, K. A1 - Lawton, D. A1 - Kofman, R. T1 - 3D Active Source Seismic Imaging of the Alpine Fault Zone and the Whataroa Glacial Valley in New Zealand N2 - The Alpine Fault zone in New Zealand marks a major transpressional plate boundary that is late in its typical earthquake cycle. Understanding the subsurface structures is crucial to understand the tectonic processes taking place. A unique seismic survey including 2D lines, a 3D array, and borehole recordings, has been performed in the Whataroa Valley and provides new insights into the Alpine Fault zone down to ∼2 km depth at the location of the Deep Fault Drilling Project (DFDP)-2 drill site. Seismic images are obtained by focusing prestack depth migration approaches. Despite the challenging conditions for seismic imaging within a sediment filled glacial valley and steeply dipping valley flanks, several structures related to the valley itself as well as the tectonic fault system are imaged. A set of several reflectors dipping 40°–56° to the southeast are identified in a ∼600 m wide zone that is interpreted to be the minimum extent of the damage zone. Different approaches image one distinct reflector dipping at ∼40°, which is interpreted to be the main Alpine Fault reflector located only ∼100 m beneath the maximum drilled depth of the DFDP-2B borehole. At shallower depths (z < 0.5 km), additional reflectors are identified as fault segments with generally steeper dips up to 56°. Additionally, a glacially over-deepened trough with nearly horizontally layered sediments and a major fault (z < 0.5 km) are identified 0.5–1 km south of the DFDP-2B borehole. Thus, a complex structural environment is seismically imaged and shows the complexity of the Alpine Fault at Whataroa. KW - Imaging KW - Signal processing KW - Seismic KW - Borehole KW - DAS PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-539163 DO - https://doi.org/10.1029/2021JB023013 VL - 126 IS - 12 SP - 1 EP - 21 PB - American Geophysical Union AN - OPUS4-53916 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -