[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter
| Autor: | Karina H. Vase, Dan Peters, Aage Kristian Olsen Alstrup, Dirk Bender, Elsebet Ø. Nielsen |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Stereochemistry Swine In vivo Desipramine medicine Animals Radiology Nuclear Medicine and imaging Tissue Distribution Carbon Radioisotopes Rats Wistar Brain uptake Norepinephrine Plasma Membrane Transport Proteins medicine.diagnostic_test biology Chemistry business.industry Reboxetine Radiosynthesis Brain Pet imaging Octanes Molecular Imaging Rats Norepinephrine transporter Positron emission tomography Organ Specificity Isotope Labeling Positron-Emission Tomography biology.protein Molecular Medicine Female Radiopharmaceuticals Nuclear medicine business medicine.drug |
| Zdroj: | Vase, K H, Peters, D, Nielsen, E Ø, Alstrup, A K O & Bender, D 2014, ' [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter ', Nuclear Medicine and Biology, vol. 41, pp. 758-764 . https://doi.org/10.1016/j.nucmedbio.2014.06.004 |
| ISSN: | 1872-9614 |
| DOI: | 10.1016/j.nucmedbio.2014.06.004 |
| Popis: | 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).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. 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 ( |
| Databáze: | OpenAIRE |
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