[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter |
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| Affiliation: | 1. PET Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark;2. DanPET AB, Rosenstigen 7, SE-216 19 Malmö, Sweden;3. NeuroSearch A/S, Pederstrupsvej 93, DK-2750 Ballerup, Denmark;1. Department of Transplant Biology, Immunology & Stem Cell Lab, Global Hospitals, Hyderabad, India;2. KK Nuclear Scans, Raj Bhavan Road, Somajiguda, Hyderabad, India;3. Cancer Centre, GA Regents University, Augusta, GA, USA;1. Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan;2. Oxford Center for Functional Magnetic Resonance Imaging of the Brain and Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom;3. Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan;4. Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan;5. Center for Optoelectronic Biomedicine, National Taiwan University Hospital, Taipei, Taiwan;6. Department of Anatomy and Cell Biology, National Taiwan University Hospital, Taipei, Taiwan;1. CHU de Bordeaux, Service de Médecine Nucléaire, F-33604 Pessac, France;2. Université de Bordeaux 2, Centre de Recherche Cardio-Thoracique, F-33076 Bordeaux, France;3. INSERM U 1045, Centre de Recherche Cardio-Thoracique, F-33076 Bordeaux, France |
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| Abstract: | IntroductionPositron 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.MethodsLabeling 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).ResultsThe 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.ConclusionBased on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET. |
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