[11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

Publication: Research - peer-reviewJournal article

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.
Original languageEnglish
JournalNuclear Medicine and Biology
Volume41
Pages (from-to)758-764
ISSN0969-8051
DOIs
StatePublished - 31 Aug 2014

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