Karina Højrup Vase

Aarhus University Hospital, Aarhus, Central Jutland, Denmark

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Publications (8)30.86 Total impact

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    ABSTRACT: Introduction Positron emission tomography (PET) imaging of the norepinephrine transporter (NET) is still hindered by the availability of useful PET imaging probes. The present study describes the radiosynthesis and pre-clinical evaluation of a new compound, exo-3-(6-methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. Methods Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate in a Boc-protected precursor. The isolated [11C]NS8880 was evaluated pre-clinically both in a pig model (PET scanning) and in a rat model (μPET scanning) and compared to (S,S)-[11C]-O-methylreboxetine ([11C]MeNER). Results The radiolabeling technique yielded [11C]NS8880 in low (< 10%) but still useful yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. Conclusion Based on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET.
    Nuclear Medicine and Biology. 01/2014;
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    ABSTRACT: The range of materials susceptible to electrochemically assisted grafting onto carbon materials has been expanded to include a new group of compounds. This new approach is based on the reduction of symmetrical or unsymmetrical triarylsulfonium salts and alkyldiphenylsulfonium salts. Our findings suggest that it is possible to form layers of aryl moieties on the surface and that the unsymmetrical triarylsulfonium salts cleave upon reduction in a direction dictated by the substituent on the rings (i.e., (4-methoxyphenyl)diphenylsulfonium salt leads to a film made predominantly of phenyl groups, whereas (4-chlorophenyl)diphenylsulfonium salt leads to a mixture of phenyl and chlorophenyl groups). These relationships may be understood by considering the inductive nature of the substituent with regard to the aryl-S bonds and are supported by preparative experiments. Upon reduction, the alkyldiphenylsulfonium salts are found to cleave almost exclusively to an alkyl radical and diphenyl sulfide. As judged from the electrochemical blocking properties of the films made from such species, either relatively thick or compact films are formed. The mass spectrometric analysis indicates that the films are made of a combination of alkyl and aryl groups and possibly related structural derivatives. Importantly, our findings provide evidence that it is possible to graft electrode surfaces with reactive aryl radicals even using precursors reduced at potentials that are substantially more negative than the estimated reduction potential of the grafting radical.
    Langmuir 02/2008; 24(1):182-8. · 4.38 Impact Factor
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    ABSTRACT: The applicability and versatility of the recently communicated procedure for the grafting of conducting carbon substrates by diaryliodonium salts is expanded. We have found that several types of organic arylic layers can be formed on the carbon surface and that the chemical functionalities of the thus formed layers can be varied extensively over electron withdrawing (for example, -NO2) to electron donating (for example, -OMe) groups. A comparative study involving the grafting of aryldiazonium salts reveals that, despite the two approaches being similar, iodonium salts exhibit spontaneous grafting to a significantly lower extent. Nevertheless, the grafted layer becomes less accessible to proton transport as visualized from a greater reluctance toward the reduction of surface-confined nitro groups to amino groups in acidic medium. Employment of unsymmetrical iodonium salts opens up the interesting possibility of forming organic films consisting of a mixture of two different aryl groups. Alternatively, such composite layers may be prepared by selecting iodonium and diazonium salts with comparable reduction properties. Analysis of the surfaces is carried out by means of cyclic voltammetry, X-ray photoelectron spectroscopy, and ToF-SIMS (time-of-flight secondary-ion mass spectrometry). The ToF-SIMS analysis primarily serves to provide unambiguous evidence for the covalent attachment of the organic layers to the surface.
    Langmuir 04/2007; 23(7):3786-93. · 4.38 Impact Factor
  • Journal of the American Chemical Society 03/2007; 129(7):1888-9. · 10.68 Impact Factor
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    ABSTRACT: The hydroquinone/quinone (H2Q/Q) redox system was tethered to glassy carbon surfaces using first an electrochemical pre-oxidation treatment to afford carboxylic acid functionalities followed by immobilizing the H2Q precursor, n-(2,5-dimethoxyphenyl)alkan-1-amine (general structure: H2N–(CH2)n–C6H3(OCH3)2, n=1, 2, 4, 8, and 12), by carbodiimide chemistry and a final demethylation reaction. The resultant surfaces exhibited the expected chemical reversibility in aqueous solution with a pH-sensitive position of the formal potential (∼55mV/pH unit), and an increase in the peak potential separation going from 0.02V for n=1 to 0.21V for n=12. The films were very robust and could withstand prolonged sonication and relatively large potential excursions. While the films followed the expected kinetic distance dependence for up to 4 methylene units the electrode kinetics was faster than expected for longer alkyl spacers. We suggest that film disorder, electrode-mediating effects, and a roughened electrode material could account for these apparent inconsistencies. To further understand such effects, two complementary electrode modification strategies leading to better film ordering on carbon were adapted; immobilizing a thin layer of benzoic acid by oxidative deposition of 4-aminobenzoic acid or employing a plasma deposition process to tether an acid analogue. Analysis of the various electrodes was accomplished by electrochemical methods, atomic force microscopy, and X-ray photoelectron spectroscopy.
    Electrochimica Acta - ELECTROCHIM ACTA. 01/2007; 53(4):1680-1688.
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    ABSTRACT: A new versatile method has been developed for the electrochemically assisted grafting of carbon materials. The approach is based on the reduction of iodonium salts and allows the immobilization not only of aryl groups, such as phenyl or nitrophenyl, but also of alkynyl groups under mild conditions. In particular, the immobilization of alkynyl groups is important because such grafting cannot be accomplished using any other known reductive procedure. The electrochemical properties of the grafted surfaces with estimated coverages of (4-6) x 10(-)(10) mol cm(-)(2) are investigated against the ferrocene and Fe(CN)(6)(3)(-) solution probes. The analysis of the surfaces is carried out by means of cyclic voltammetry and X-ray photoelectron spectroscopy.
    Langmuir 09/2005; 21(18):8085-9. · 4.38 Impact Factor
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    ABSTRACT: 4,4'-Bipyridinium (i.e., viologen) was immobilized on 4-(chloromethyl)phenyl grafted glassy carbon electrodes by a nucleophilic substitution reaction involving 1-ethyl- or 1-benzyl-4-(4'-pyridyl)pyridinium. Reaction times of about 5 days were required for these surface-constrained processes to go to completion in aqueous solution at room temperature. The applicability of the described procedure was demonstrated by performing the equivalent modi. cation in 2 steps by reacting first with 4,4'-bipyridine, followed by quaternization of the available nitrogen to obtain the viologen functionality, that is, the surface acts as a nucleophile in a substitution reaction. However, the quaternization step was found to be possible for introducing the benzyl group but not the ethyl group. The covalently modified electrodes were reasonably stable to repeated electrochemical sweeping in acetonitrile with a 25% decrease in the observed electroactivity after 100 sweeps at a sweep rate of 2 V s(-1). The coverage was determined from the electrochemical response of the viologen moiety to be approximately 3 x 10(-10) mol cm(-2). In addition to cyclic voltammetry, the presence of viologen was demonstrated by means of X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. Scanning images (500 x 500 mu m(2)) obtained by the latter technique indicated that the molecules were distributed uniformly over the entire surface. Scanning tunnelling microscopy was used to follow the individual steps of the modi. cation procedure on highly ordered pyrolytic graphite.
    New Journal of Chemistry 01/2005; 29(5):659-666. · 2.97 Impact Factor
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    ABSTRACT: RationaleLack of benefit from antidepressant drug therapy is a major source of human suffering, affecting at least 25% of people with major depressive disorder. We want to know whether nonresponse to antidepressants can be linked to aberrant neuroreceptor binding. ObjectiveThis study aims to assess the antidepressant binding in brain regions of depressed nonresponders compared with healthy controls. Materials and methodsHealthy volunteers and depressed subjects who had failed to benefit from at least 2 antidepressant treatments were recruited by newspaper advertisements. All subjects had received no antidepressant medication for at least 2months before positron emission tomography (PET) that was carried out with [11C]mirtazapine. Kinetic parameters of [11C]mirtazapine were determined from PET data in selected brain regions by the simplified reference tissue model. ResultsBinding potentials of [11C]mirtazapine in cerebral cortical regions were lower in depressed nonresponders than in healthy controls. Removal rates of [11C]mirtazapine were higher in diencephalic regions of depressed nonresponders than in healthy controls. ConclusionsPET neuroimaging with [11C]mirtazapine showed aberrant neuroreceptor binding in brain regions of depressed subjects who had failed to benefit from treatment with antidepressant drugs.
    Psychopharmacology 206(1):133-140. · 4.06 Impact Factor