The Experts below are selected from a list of 54 Experts worldwide ranked by ideXlab platform
Olof Solin - One of the best experts on this subject based on the ideXlab platform.
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Comparison of 2β-Carbomethoxy-3β-(4-[^18F]Fluorophenyl)Tropane and N-(3-[^18F]Fluoropropyl)-2β-Carbomethoxy-3β-(4-Fluorophenyl)Nortropane, Tracers for Imaging Dopamine Transporter in Rat
Molecular Imaging and Biology, 2010Co-Authors: Päivi Marjamäki, Merja Haaparanta, Sarita Forsback, Veronica Fagerholm, Olli Eskola, Tove Grönroos, Teija Koivula, Olof SolinAbstract:Purpose This study compares 2β-carbomethoxy-3β-(4-[^18F]fluorophenyl)tropane ([^18F]β-CFT) and N -(3-[^18F]fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([^18F]β-CFT-FP) as radiotracers for imaging the dopamine Transporter (DAT) in rat. Procedures Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin Transporter (SERT) and Noradrenalin Transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography. Results [^18F]β-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [^18F]β-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [^18F]β-CFT also bound to NET. [^18F]β-CFT was more resistant to metabolism than [^18F]β-CFT-FP. Conclusions Structural modifications of [^18F]β-CFT significantly changed its biological properties, as shown by [^18F]β-CFT-FP. [^18F]β-CFT is a suitable tracer for both preclinical and human PET studies, but [^18F]β-CFT-FP is less suitable as a PET tracer.
Bart A. Ellenbroek - One of the best experts on this subject based on the ideXlab platform.
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Blockade of dopamine, but not Noradrenaline, Transporters produces hyperthermia in rats that lack serotonin Transporters.
European Journal of Pharmacology, 2009Co-Authors: Jocelien D. A. Olivier, Alexander R. Cools, Peter M. T. Deen, Berend Olivier, Bart A. EllenbroekAbstract:To investigate whether life-long disturbed serotonin neurotransmission may result in adaptive changes of dopaminergic and noradrenergic systems, effects of drugs on stress-induced hyperthermia were studied in serotonin Transporter knockout rats. The Noradrenalin Transporter blocker atomoxetine was more effective in reducing stress-induced hyperthermia, induced by an injection, in serotonin Transporter (SERT) knockout (SERT(-/-)) rats compared to SERT(+/+) rats. The dopamine Transporter blocker GBR12909 increased the core body temperature in SERT(-/-) rats, and had no effect on the SERT(+/+) rats. Finally, the Noradrenalin Transporter together with dopamine Transporter blocker bupropion was more effective in decreasing the stress of an injection in SERT(-/-) rats than in SERT(+/+) rats. These data suggest that the sensitivity of dopamine and Noradrenalin receptors is changed in serotonin Transporter knockout rats. The lack of the serotonin Transporter in SERT(-/-) rats might reflect humans with a life-long disturbed serotonin system, making this rat a good model to study possible changes in dopaminergic and noradrenergic systems in psychiatric disorders.
Patrick Schloss - One of the best experts on this subject based on the ideXlab platform.
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Ex vivo and in vivo evaluation of [18F]PR04.MZ in rodents: a selective dopamine Transporter imaging agent.
ChemMedChem, 2009Co-Authors: Patrick J. Riss, René Hummerich, Patrick Schloss, Fabian Debus, Ulrich Schmidt, Hartmut Lueddens, Frank RoeschAbstract:N-4-Fluorobut-2-yn-1-yl-2beta-carbomethoxy-3beta-phenyltropane (PR04.MZ) has been developed as dopamine Transporter (DAT) ligand for molecular imaging. It contains a terminally fluorinated, conformationally constrained nitrogen substituent that is well suited for the introduction of fluorine-18. The present report describes the pharmacological characterisation of [18F]PR04.MZ. The ligand shows an IC50 value of 2 nM against human DAT, whereas the IC50 value against human serotonin Transporter and human Noradrenalin Transporter are lower (110 nM and 22 nM, respectively). Furthermore, its ex vivo organ distribution, its binding profile in the rat brain and reversibility of binding were examined. A muPET study illuminates a fast kinetic profile and specific binding to rat DAT.
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Synthesis and monoamine uptake inhibition of conformationally constrained 2β-carbomethoxy-3β-phenyl tropanes
Organic & biomolecular chemistry, 2009Co-Authors: Patrick J. Riss, René Hummerich, Patrick SchlossAbstract:A series of 2β-carbomethoxy-3β-phenyl tropanes with conformationally constrained nitrogen substituents were synthesized as potential selective dopamine Transporter ligands. These novel compounds were examined for their monoamine uptake inhibition potency at the human dopamine Transporter (hDAT), the human serotonin Transporter (hSERT) and the human Noradrenalin Transporter (hNET), stably expressed in human embryonic kidney cells (HEK). A SAR-study was conducted to determine the contribution of extended, 4-fluorinated, conformationally constrained C4 chains at the tropane nitrogen to human monoamine Transporter affinity and selectivity.
Päivi Marjamäki - One of the best experts on this subject based on the ideXlab platform.
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Comparison of 2β-Carbomethoxy-3β-(4-[^18F]Fluorophenyl)Tropane and N-(3-[^18F]Fluoropropyl)-2β-Carbomethoxy-3β-(4-Fluorophenyl)Nortropane, Tracers for Imaging Dopamine Transporter in Rat
Molecular Imaging and Biology, 2010Co-Authors: Päivi Marjamäki, Merja Haaparanta, Sarita Forsback, Veronica Fagerholm, Olli Eskola, Tove Grönroos, Teija Koivula, Olof SolinAbstract:Purpose This study compares 2β-carbomethoxy-3β-(4-[^18F]fluorophenyl)tropane ([^18F]β-CFT) and N -(3-[^18F]fluoropropyl)-2β-carbomethoxy-3β-(4-fluorophenyl)nortropane ([^18F]β-CFT-FP) as radiotracers for imaging the dopamine Transporter (DAT) in rat. Procedures Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin Transporter (SERT) and Noradrenalin Transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography. Results [^18F]β-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [^18F]β-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [^18F]β-CFT also bound to NET. [^18F]β-CFT was more resistant to metabolism than [^18F]β-CFT-FP. Conclusions Structural modifications of [^18F]β-CFT significantly changed its biological properties, as shown by [^18F]β-CFT-FP. [^18F]β-CFT is a suitable tracer for both preclinical and human PET studies, but [^18F]β-CFT-FP is less suitable as a PET tracer.
Jocelien D. A. Olivier - One of the best experts on this subject based on the ideXlab platform.
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Blockade of dopamine, but not Noradrenaline, Transporters produces hyperthermia in rats that lack serotonin Transporters.
European Journal of Pharmacology, 2009Co-Authors: Jocelien D. A. Olivier, Alexander R. Cools, Peter M. T. Deen, Berend Olivier, Bart A. EllenbroekAbstract:To investigate whether life-long disturbed serotonin neurotransmission may result in adaptive changes of dopaminergic and noradrenergic systems, effects of drugs on stress-induced hyperthermia were studied in serotonin Transporter knockout rats. The Noradrenalin Transporter blocker atomoxetine was more effective in reducing stress-induced hyperthermia, induced by an injection, in serotonin Transporter (SERT) knockout (SERT(-/-)) rats compared to SERT(+/+) rats. The dopamine Transporter blocker GBR12909 increased the core body temperature in SERT(-/-) rats, and had no effect on the SERT(+/+) rats. Finally, the Noradrenalin Transporter together with dopamine Transporter blocker bupropion was more effective in decreasing the stress of an injection in SERT(-/-) rats than in SERT(+/+) rats. These data suggest that the sensitivity of dopamine and Noradrenalin receptors is changed in serotonin Transporter knockout rats. The lack of the serotonin Transporter in SERT(-/-) rats might reflect humans with a life-long disturbed serotonin system, making this rat a good model to study possible changes in dopaminergic and noradrenergic systems in psychiatric disorders.
