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Nucl Med Biol. 2014 Oct;41(9):758-64. doi: 10.1016/j.nucmedbio.2014.06.004. Epub 2014 Jun 25.

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

Author information

1
PET Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. Electronic address: karina@pet.auh.dk.
2
DanPET AB, Rosenstigen 7, SE-216 19 Malmö, Sweden.
3
NeuroSearch A/S, Pederstrupsvej 93, DK-2750 Ballerup, Denmark.
4
PET Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.

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 [(11)C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [(11)C]methanolate in a Boc-protected precursor. The isolated [(11)C]NS8880 was evaluated pre-clinically both in a pig model (PET scanning) and in a rat model (μPET scanning) and compared to (S,S)-[(11)C]-O-methylreboxetine ([(11)C]MeNER).

RESULTS:

The radiolabeling technique yielded [(11)C]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 [(11)C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [(11)C]NS8880.

CONCLUSION:

Based on the pre-clinical results obtained so far [(11)C]NS8880 displays promising properties for PET imaging of NET.

KEYWORDS:

MeNER; NS8880; Norepinephrine transporter; PET; Preclinical evaluation; Radiosynthesis

PMID:
25127515
DOI:
10.1016/j.nucmedbio.2014.06.004
[Indexed for MEDLINE]

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